ARRAY 818-103: A Sequential 2-arm, Open-label Phase 1 Study to Evaluate the Effects of Encorafenib in Combination with Binimetinib on the Pharmacokinetics of Losartan, Midazolam, Caffeine, Omeprazole, and Dextromethorphan Administered in a Cocktail Approach and on the Pharmacokinetics of Rosuvastatin in Patients with BRAF V600-mutant Unresectable or Metastatic Melanoma or Other Advanced Solid Tumors
Principal Investigator: Arek Dudek, MD, PhD
Study Sponsor: ARRAY Pharmaceuticals, Inc.
Location: Regions Cancer Care Center (Regions Hospital)
Phase of Study: Phase 1
Purpose of Study: To assess the effect of encorafenib and binimetinib (the study drugs) on the activity of other common drugs. This study will also look at the safety and how you tolerate the study drugs when administered with the other common drugs. These other common drugs are approved by the FDA and include losartan (a drug used to treat high blood pressure), dextromethorphan (a drug used to treat coughs), caffeine (about the same amount as a cup of coffee), omeprazole (a drug used to treat upset stomach), midazolam (a drug used as a sedative), and rosuvastatin (a drug used to treat high cholesterol).
The study drugs are investigational study drugs, meaning that they have not been approved by the United States Food and Drug Administration (FDA).
Inclusion Criteria:
– Male or female patient, age ≥ 18 years;
– Histologically confirmed diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or unknown primary melanoma AJCC Stage IIIB, IIIC or IV; or other BRAF V600-mutant advanced solid tumors;
– Presence of BRAF V600E and/or V600K mutation in tumor tissue prior to enrollment, as determined locally using an approved test;
– Evidence of measurable or non-measurable lesions as detected by radiological or photographic methods according to guidelines based on RECIST v. 1.1;
– Patient with unresectable locally advanced or metastatic melanoma who has received no prior treatment or progressed on or after prior systemic therapy. Note: Prior therapy with a BRAF inhibitor (e.g., vemurafenib,dabrafenib, encorafenib and XL281/BMS-908662) and/or a MEK inhibitor (e.g., trametinib, binimetinib, selumetinib, cobimetinib and refametinib) is permitted except in the regimen immediately prior to study entry. Progression during prior BRAF/MEK inhibitor treatment is not required;
– Patient with other (non-melanoma) BRAF V600-mutant advanced solid tumors who has progressed on standard therapy or for whom there are no available standard therapies. Note: Prior therapy with a BRAF inhibitor and/or a MEK inhibitor is permitted except in the regimen immediately prior to study entry.
– Progression during prior BRAF/MEK inhibitor treatment is not required; if it occurred, the patient’s circumstances (e.g., ≥ 1 year since prior BRAF and/or MEK inhibitor, equivocal progression, refractory to available therapies) must be discussed with the Sponsor prior to
– enrollment;
– Non-smoker who has not used nicotine containing products for at least 3 months prior to the first dose;
– ECOG PS of 0 or 1;
– Adequate bone marrow, organ function and laboratory parameters:
– Able to take oral medications;
– Patient is deemed by the Investigator to have the initiative and means to be compliant with the protocol (treatment and follow-up);
– Negative serum beta-human chorionic gonadotropin (β-HCG) test 72 hours prior to first dose and consent to ongoing urine pregnancy testing during the course of the study;
– Male patients and female patients of childbearing potential must agree to use an acceptable method of contraception as defined in the study protocol.
Exclusion Criteria:
-Symptomatic brain metastasis. Patients previously treated or untreated for these conditions who are asymptomatic in the absence of corticosteroid and anti-epileptic therapy are allowed. Brain metastases must be stable, with imaging (MRI or CT) demonstrating no current evidence of progressive brain metastases at screening;
– History of reaction to any of the study medications being used in this trial;
– Use, within 2 weeks prior to the start of treatment (Day -14) and through DDI phase (Day 28), of any herbal medications/supplements or any medications or foods that are strong inhibitors or inducers of CYP3A4/5, strong inhibitors of UGT1A1 and substrates of CYP3A4, CYP2C9, CYP1A2, CYP2C19, CYP2D6, BCRP, P-glycoprotein (P-gp), organic anion transporters 1 and 3 (OAT1, OAT3), organic anion transporter 2 (OCT2), OATP1B1 and OATP1B3.
– Consumption of grapefruit, pomegranates, star fruits, Seville oranges or products containing the juice of each starting from Day -14 and through the DDI phase (Day 28), due to potential CYP3A4 interaction with the study drugs. Orange juice is allowed;
– Symptomatic or untreated leptomeningeal disease;
– History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes);
– Clinically significant cardiac disease
– Impaired hepatic function as defined by Child-Pugh class B or C;
– Impaired gastrointestinal function or disease which may significantly alter the absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection);
– History of thromboembolic or cerebrovascular events within the prior 6 months, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis, or pulmonary emboli;
– Nitrosourea or mitomycin-C within 6 weeks prior to start of study drug
– Other chemotherapy, radiation therapy that included > 30% of the bone marrow reserve, or biological therapy (e.g., antibodies) within 4 weeks prior to start of study drug
– Continuous or intermittent small-molecule therapeutics or investigational agents within 5 half-lives of the agent (or within 4 weeks prior to start of study drug, when half-life is unknown)
– Grade 2 side effects of any such therapy (residual Grade 2 alopecia is permitted);
– Discontinuation of prior BRAF and/or MEK inhibitor treatment due to toxicity;
– Known positive serology for human immunodeficiency virus (HIV) infection, active hepatitis B and/or active hepatitis C infection;
– Positive urine cotinine test at screening;
– History of Gilbert’s syndrome;
– Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgement of the Investigator, would make the patient inappropriate for the study;
– Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until termination of gestation, confirmed by a positive β-hCG laboratory test (> 5 mIU/mL).
Study Contact:
Lisa Wahowske, RN, BSN, OCN
(651) 254-1517
Lisa.Wahowske@ParkNicollet.com
ASTELLAS 8951-CL-0301 (Spotlight)
Principal Investigator: Daniel Anderson, MD
Study sponsor: Astellas
Location: Frauenshuh Cancer Center
Phase of Study: Phase 3
Purpose of study: A study to assess the efficacy of IMAB362 plus mFOLFOX6 compared with placebo plus mFOLFOX6 as first-line treatment of subjects with Claudin (CLDN) 18.2 positive, HER2-negative, locally advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (Spotlight).
Inclusion Criteria:
Waivers to the inclusion criteria will NOT be allowed.
– Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations (e.g., HIPAA Authorization for US sites) must be obtained from the subject or legally authorized representative (if applicable) prior to any study-related procedures.
– Subject is considered an adult (e.g., ≥ 18 years of age in the US) according to local regulation at the time of signing the informed consent.
– Subject agrees not to participate in another interventional study while on study treatment.
– A female subject is eligible to participate if she is not pregnant (negative serum pregnancy test at screening; female subjects with elevated serum beta human chorionic gonadotropin (βhCG) and a demonstrated non-pregnant status through additional testing are eligible) and at least 1 of the following conditions applies:
a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 12.3 Contraception Requirements OR
b. WOCBP who agrees to follow the contraceptive guidance as defined in Appendix 12.3 Contraception Requirements throughout the treatment period and for at least 6 months after the final study drug administration.
– Female subject must agree not to breastfeed starting at Screening and throughout the study period, and for 6 months after the final study treatment administration.
– Female subject must not donate ova starting at Screening and throughout the study period, and for 6 months after the final study drug administration.
– A sexually active male subject with female partner(s) who are of childbearing potential must agree to use contraception as detailed in Appendix 12.3 Contraception Requirements during the treatment period and for at least 6 months after the final study drug administration.
– Male subject must not donate sperm starting at Screening and throughout the study period and for 6 months after the final study drug administration.
– Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or for the time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration.
Disease Specific Criteria:
– Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
– Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to the first dose of study treatment.
– Subject has measurable disease according to RECIST 1.1 within 28 days prior to the first dose of study treatment. For subjects with only 1 measurable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
– Subject’s tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing.
– Subject has a HER2-Negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen.
Physical or Laboratory Findings
– Subject has ECOG performance status 0 to 1.
– Subject has predicted life expectancy 12 weeks in the opinion of the investigator.
– Subject must meet all of the following criteria based on the centrally analyzed laboratory tests within 14 days prior to the first dose of study treatment. In case of multiple laboratory data within this period, the most recent data should be used to determine eligibility.
a. Hemoglobin (Hgb) ≥ 9 g/dL. NOTE: subject must not have received any growth factor or blood transfusions within 14 days prior to the hematology values obtained at screening. Subjects requiring transfusions to meet eligibility criteria are not eligible.
b. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
c. Platelets ≥ 100 x 109/L
d. Albumin ≥ 2.5 g/dL
e. Total bilirubin < 1.5 x upper limit of normal (ULN)
f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN without liver metastases (or ≤ 5 x ULN if liver metastases are present)
g. Estimated creatinine clearance ≥ 30 mL/min
h. PT/international normalized ratio (INR) and PTT ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)
Exclusion Criteria:
Waivers to the exclusion criteria will NOT be allowed.
Subject who meets any of the following exclusion criteria prior to enrollment is not eligible for enrollment:
Prohibited Treatment or Therapies
– Subject has received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. However, subject may have received either neo-adjuvant or adjuvant chemotherapy as long as it was completed at least 6 months prior to the first dose of study treatment. Subject may have received treatment with herbal medications that have known antitumor activity > 28 days prior to first dose of study treatment.
– Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma unless the radiotherapy was completed >28 days prior to start of study treatment. Subject who received palliative radiotherapy to peripheral bone metastases ≥14 days prior to start of study treatment and has recovered from all acute toxicities is allowed.
– Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to first dose of study treatment. Subjects using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone) or a single dose of systemic corticosteroids are allowed.
– Subject has received other investigational agents or devices within 28 days prior to first dose of study treatment.
Medical History or Concurrent Disease
– Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
– Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
– Subject has prior severe allergic reaction or intolerance to any component of mFOLFOX6.
– Subject has known dihydropyrimidine dehydrogenase (DPD) deficiency. (NOTE: Screening for DPD deficiency should be conducted per local requirements.)
– Subject has gastric outlet syndrome or persistent/recurrent vomiting.
– Subject with recent gastric bleeding or symptomatic subjects with proven gastric ulcers that would exclude the subject from participation per investigator judgment.
– Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection or known active hepatitis B (positive HBs Ag) or C infection. For subjects who are negative for HBs Ag, but HBc Ab positive, an HB DNA test will be performed and if positive the subject will be excluded. Subjects with positive serology but negative HCV RNA test results are eligible.
– Subject has an active autoimmune disease that has required systemic treatment within the past 2 years.
– Subject has active infection requiring systemic therapy that has not completely resolved within 14 days prior to start of study treatment.
– Subject has significant cardiovascular disease, including any of the following:
a. Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to administration of first dose of study drug.
b. History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes)
c. QTc interval > 450 msec for male subjects; QTc interval > 470 msec for female subjects
d. History or family history of congenital long QT syndrome
e. Cardiac arrhythmias requiring anti-arrhythmic medications (Subject with rate controlled atrial fibrillation for > 1 month prior to first dose of study drugs are eligible)
– Subject has known active central nervous system metastases and/or carcinomatous meningitis.
– Subject has known peripheral sensory neuropathy > Grade 1 unless the absence of deep tendon reflexes is the sole neurological abnormality.
– Subject has had a major surgical procedure 28 days prior to the start of study treatment.
a. Subject is without complete recovery from a major surgical procedure 14 days prior to the first dose of study treatment.
– Subject has psychiatric illness or social situations that would preclude study compliance, per investigator judgment.
– Subject has another malignancy for which treatment is required per investigator’s clinical judgment.
– Subject has any concurrent disease, infection or comorbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data in the opinion of the investigator.
Study Contact:
Alissa Gavenda
(952) 993-6705
Alissa.Gavenda@ParkNicollet.com
Connect® MDS and AML: The Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) Disease Registry
Principal Investigator: Dylan Zylla, MD
Study Sponsor: Celgene Corporation
Location: Frauenshuh Cancer Center (Methodist Hospital)
Phase of Study: Phase 3
Purpose of Study: There are three main purposes of this study: (1) To use the information collected to better understand patterns of diagnosis, treatment and outcomes, including disease progression and survival, in patients with MDS and AML; (2) To use the information to better understand patterns of quality of life in patients newly diagnosed with lower-risk MDS, higher-risk MDS, ICUS [Idiopathic Cytopenia of Undetermined Significance] or AML; and (3) To use the results of this study to provide information to better understand the effects of different treatments on a patient’s disease and quality of life. This study does not involve any treatment. Any current treatment will not be affected by participation in this registry study.
Study Contact:
Grant Simonson
(952) 993-6723
Grant.Simonson@ParkNicollet.com
Exact Sciences 2018-01
Principal Investigator: Rachel Lerner, MD
Study sponsor: Exact Sciences
Location: Frauenshuh Cancer Center
Purpose of study: The primary objective of this study is to obtain de-identified, clinically characterized, whole blood specimens to evaluate biomarkers associated with cancer for diagnostic assay development.
Inclusion Criteria:
-Subject is male or female > 18 years of age.
-Subject has an untreated primary malignancy of breast, lung, colorectal, prostate, bladder, uterine, kidney/renal pelvis, pancreatic, liver, stomach, ovarian or esophageal cancer.
-Subject understands the study procedures and is able to provide informed consent to participate in the study and authorization for release of relevant protected health information to the study Investigator.
Exclusion Criteria:
-Any previous cancer diagnosis within the past 5 years (with the exceptions of basal cell or squamous cell skin cancers).
-Chemotherapy and/or radiation therapy within 5 years prior to enrollment/sample collection.
-Any treatment for the primary malignancy or sites of metastases. Subject may not have started neo-adjuvant chemotherapy, neo-adjuvant radiation therapy, immunotherapy or other treatment and/or surgery prior to blood sample collection.
-Less than 3 days between fine needle aspiration (FNA) of target pathology and blood collection.
-Less than 7 days between biopsy (other than FNA) of target pathology and blood collection.
-IV contrast (e.g. CT and MRI) within 1 day [or 24 hours] of blood collection.
-Individual has a condition the Investigator believes would interfere with his or her ability to provide informed consent, comply with the study protocol, which might confound the interpretation of the study results or put the person at undue risk.
Study Contact:
Janet Morgan
(952) 993-1737
Janet.Morgan@ParkNicollet.com
GU15-215: A Randomized Phase II Trial of Atezolizumab with or without Bevacizumab in Cisplatin-ineligible Patients with Advanced/Unresectable Urothelial Cancer
Principal Investigator: Arek Dudek, MD, PhD
Study Sponsor: Hoosier Cancer Research Network
Location: Regions Cancer Care Center (Regions Hospital)
Phase of Study: Phase 2
Purpose of Study:
To compare any good and bad effects of treating your type of cancer with atezolizumab alone versus atezolizumab plus bevacizumab. Atezolizumab is already an FDA approved standard treatment for advanced urothelial cancer for people who cannot safely receive cisplatin chemotherapy. Bevacizumab is not FDA approved standard treatment for urothelial cell carcinoma. In this study, you will receive atezolizumab or atezolizumab plus bevacizumab as the first treatment for your advanced urothelial cancer. Bevacizumab plus atezolizumab has been shown to be safe in previous studies in patients with other type of cancers. The study doctors would like to determine if the combination of atezolizumab and bevacizumab is more effective in controlling your cancer than using atezolizumab alone.
Inclusion Criteria:
– Age ≥ 18 years at the time of consent
– Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2 within 28 days prior to randomization
– Histological or cytological evidence urothelial (transitional cell) carcinoma of the renal pelvis, ureter, bladder or urethra
– Locally advanced/unresectable disease as determined by site attending urologic oncologist or metastatic disease
– Evaluable untreated tumor tissue for biomarker analysis. Untreated tumor tissue is defined as no intervening intravesical or systemic therapy since acquisition. Patients without tissue available must be willing and safe to undergo biopsy repeat biopsy (core needle or excisional) prior to enrollment. Subjects with < 25 slides may be enrolled after discussion with the sponsor-investigator or co-investigator.
– Willing to undergo a core needle or excisional biopsy on-treatment. Patients will be assessed at the time of biopsy for safety of undergoing the procedure
– Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 within 28 days prior to randomization
– No prior chemotherapy for locally advanced or metastatic urothelial cancer
– Ineligible for cisplatin as defined by presence of one or more of the following:
– If palliative radiotherapy administered, completion of palliative radiation therapy ≥ 2 weeks prior to Cycle 1 Day 1 of protocol therapy
– Females of childbearing potential must have a negative serum pregnancy test within 28 days prior to registration.
– Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 120 days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method
Exclusion Criteria:
– Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment; the following exceptions are allowed:
– Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
– Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) scan or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments. Patients with treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:
– Leptomeningeal disease
– Uncontrolled tumor-related pain
– Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
– Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab.
– Malignancies other than urothelial cancer within 5 years prior to Cycle 1 Day 1, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (T1/T2a, Gleason score ≤ 3 + 4, and PSA ≤ 0.5 ng/mL undergoing active surveillance and treatment naive)
– Pregnant or breastfeeding
– History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
– Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab or bevacizumab formulation
– History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, granulomatosis with polyangiitis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
– History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
– History of confirmed positive test for human immunodeficiency virus (HIV)
– Patients with active hepatitis B virus (HBV) (chronic or acute, defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C virus (HCV)
– Active tuberculosis
– Severe infections within 4 weeks prior to Cycle 1 Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
– Signs or symptoms of active infection within 2 weeks prior to C1D1
– Received therapeutic oral or IV antibiotics within 1 week prior to C1D1
– New York Heart Association Congestive Heart Failure Class II or greater
– Myocardial infarction, unstable angina or unstable arrhythmias within 3 months of enrollment.
– History of stroke or TIA within 3 months of enrollment
– Other clinically significant arterial vascular disease within 6 months of enrollment (e.g. aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis). Prior history of adequately treated venous thromboembolism > 7 days prior to C1D1 on stable dose of therapeutic anticoagulation is permitted
– Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
– Major surgical procedure other than for diagnosis within 28 days prior to C1D1 or anticipation of need for a major surgical procedure during the course of the study
– Prior allogeneic stem cell or solid organ transplant
– Administration of a live, attenuated vaccine within 4 weeks before C1D1 or anticipation that such a live attenuated vaccine will be required during the study
– Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications
Study Contact:
Lisa Wahowske, RN, BSN, OCN
(651) 254-1517
Lisa.Wahowske@ParkNicollet.com
KRT-232-101: An Open-Label, Phase 2a/2b Study of KRT-232 in Subjects With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PVMF), Or Post-Essential Thrombocythemia MF (Post-ET-MF) Who Have Failed Prior Treatment with a JAK Inhibitor (KRT-232-101)
Principal Investigator: Yan Ji, MD
Study Sponsor: Kartos Therapeutics, Inc.
Location: Regions Cancer Care Center
Phase of Study: Phase 2
Purpose of Study: In this study, we want to find out how well a drug called KRT-232 is tolerated when given to patients with (myelofibrosis) MF and whether KRT-232 can improve your MF. KRT-232 (previously called AMG 232) is investigational and is not approved by the U.S. Food and Drug Administration (FDA). This is the first study of KRT-232 in MF and it will evaluate how well tolerated KRT-232 is when given to participants with MF, and whether KRT-232 can improve your MF. KRT-232 has been given to about 170 participants with different cancers and disorders (other than MF). Some of these studies are ongoing. KRT-232 is a small molecule inhibitor and can reverse a mechanism through which unhealthy or tumor cells can survive and grow. This study will test if KRT-232 can restore the function of your healthy bone marrow cells and reduce the symptoms of your MF. This study will test different doses and schedules of KRT-232 in 3 groups of participants to identify the recommended dose and schedule.
Inclusion Criteria:
-Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)
-High, intermediate-2, or intermediate-1 risk Dynamic International Prognostic System (DIPSS)
-Failure of prior treatment with JAK inhibitor (Part A) or ruxolitinib (Part B)
-ECOG ≤ 2
Exclusion Criteria:
-Prior splenectomy
-Splenic irradiation within 3 months prior to the first dose of KRT-232
-Active or chronic bleeding within 4 weeks prior to the first dose of KRT-232
-Prior MDM2 inhibitor therapy or p53-directed therapy
-Prior treatment with HDAC or BCL-2 inhibitors
-Grade 2 or higher QTc prolongation (> 480 milliseconds per NCI-CTCAE criteria, version 5.0)
Study Contact:
Lisa Wahowske, RN, BSN, OCN
(651) 254-1517
Lisa.Wahowske@ParkNicollet.com
MK3475-564: A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (KEYNOTE-564)
Principal Investigator: Dan Anderson, MD
Phase of Study: Phase 3
Study Sponsor: Merck Pharmaceuticals
Location: Frauenshuh Cancer Center (Methodist Hospital)
Purpose of Study: To test the safety and tolerability of pembrolizumab/KEYTRUDA® and to test the effectiveness of pembrolizumab/KEYTRUDA® compared to placebo (sugar pill). In this study, Pembrolizumab/KEYTRUDA® is considered to be Investigational, meaning that it has not been approved for use in kidney cancer by the United States Food and Drug Administration (FDA).
You will be assigned by chance (like the flip of a coin) to receive either 200 mg of pembrolizumab/KEYTRUDA® or placebo. You have a one in two chance of getting placebo. Neither you nor the study doctor will know which you are receiving. In case of an emergency, the study doctor can get this information.
Inclusion Criteria:
– Has histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features.
– Female participants of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study treatment.
– Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study treatment through 120 days after the last dose of study treatment.
– Has intermediate-high risk, high risk, or M1 NED RCC as defined by the following pathological tumor-node-metastasis and Fuhrman grading status:
1. Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, Any Grade, N0, M0
2. High risk RCC: pT4, Any Grade N0, M0; pT, Any stage, Any Grade, N+, M0
3. M1 NED RCC participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at one of the following: the time of nephrectomy (synchronous) or, ≤1 year from nephrectomy (metachronous).
– Has received no prior systemic therapy for advanced RCC.
– Has undergone a partial nephroprotective or radical complete nephrectomy (and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants) with negative surgical margins.
– Must have undergone a nephrectomy and/or metastasectomy ≥28 days prior to signing informed consent and ≤12 weeks prior to randomization.
– Must be tumor-free as assessed by the Investigator and validated by either computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain and chest, abdomen, and pelvis and a bone scan ≤28 days from randomization.
– Must have provided adequate tissue per the following: Nephrectomy only: tissue from nephrectomy (required); Synchronous M1 NED: tissue from nephrectomy (required) AND, metastasectomy tissue (if available); Metachronous M1 NED: tissue from metastasectomy (required) AND, nephrectomy tissue (if available).
– Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1.
– Has adequate organ function.
Exclusion Criteria:
– Has had major surgery, other than nephrectomy and/or resection of pre-existing metastases for M1 NED participants, within 12 weeks prior to randomization.
– Has received prior radiotherapy for RCC.
– Has pre-existing brain or bone metastatic lesions.
– Has residual thrombus post nephrectomy in the vena renalis or vena cava.
– Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment.
– Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy is allowed.
– Has a known additional malignancy that is progressing or required active treatment ≤3 years ago. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer, or in situ breast cancer that has undergone potentially curative therapy.
– Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
– Has an active infection requiring systemic therapy.
– Has a history of, or is currently on, dialysis.
– Has a known history of human immunodeficiency virus (HIV) infection.
– Has known active hepatitis B or hepatitis C virus infection.
– Has a known history of active tuberculosis (Bacillus tuberculosis).
– Has had a prior solid organ transplant.
– Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
– Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the Screening visit through 120 days after the last dose of study treatment.
– Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137 [tumor necrosis factor receptor superfamily member 9 (TNFRSF9)]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial.
– Has received prior anticancer therapy, monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before first dose of study treatment or not recovered (i.e., must be ≤ Grade 1 or at Baseline) from AEs due to previously administered agents.
– Has received a live vaccine within 30 days prior to the first dose of study treatment.
– Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
Study Contact:
Alissa Gavenda
(952) 993-6705
Alissa.Gavenda@ParkNicollet.com
Mayo Clinic MC17C1
Principal Investigator: Dylan Zylla, MD
Study sponsor: Mayo Clinic
Locations:
-Frauenshuh Cancer Center
-Regions Cancer Care Center
Phase of Study: Phase 1
Purpose of study: This early phase I trial studies the side effects of ketoconazole and how well it works in treating participants with ongoing EGFR inhibitor-induced rash. Ketoconazole may reduce the symptoms related to EGFR inhibitor therapy and improve EGFR inhibitor-induced rash.
Inclusion Criteria:
-Patient has developed a rash or symptoms of a rash (cutaneous burning) characteristic of an EGFR inhibitor (health-care provider report of the rash with no other documentation is permitted).
-Patient is anticipated to continue for at least 28 days with an EGFR inhibitor or restart? 14 days of registration and continue for at least 28 days.
-Patient is willing to provide a skin biopsy for correlative research; Note: Can be waived with permission of study chair (documentation such as an email must be provided).
-Patient must complete baseline quality of life (QOL) packet.
Exclusion Criteria:
-Patient has a prior allergy or intolerance of ketoconazole.
-Patient has an allergy or intolerance to sulfites.
Study Contact:
Grant Simonson
(952) 993-6723
Grant.Simonson@ParkNicollet.com
Merck LEAP 007
Principal Investigator: Daniel Anderson, MD
Study sponsor: Merck Sharpe and Dohme Corp
Location: Frauenshuh Cancer Center
Phase: Phase 3
Purpose of study: The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for lenvatinib) in the treatment in treatment-naïve adults with no prior systemic therapy for their metastatic non-small cell lung cancer (NSCLC) whose tumors have a programmed cell death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) greater than or equal to 1%.
Inclusion Criteria:
– Has a histologically or cytologically confirmed diagnosis of NSCLC.
– Has Stage IV NSCLC (American Joint Committee on Cancer [AJCC]).
– Has measurable disease based on RECIST 1.1.
– Has tumor tissue that demonstrates programmed cell death-ligand 1 (PD-L1) expression in ≥1% of tumor cells (Tumor Proportion Score [TPS] ≥1%) as assessed by immunohistochemistry (IHC) 22C3 pharmDx assay (Dako North America, Inc.) at a central laboratory.
– Has a life expectancy of ≥3 months.
– Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before the first dose of study treatment but before randomization.
– Male participants must agree to the following during the treatment period and for at least 120 days after the last dose of study treatment: 1.) Must be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent OR 2.) Must agree to use study-approved contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) AND 3.) Must refrain from donating sperm for at least 120 days after the last dose of lenvatinib.
– Female participants are eligible if they are not pregnant or breastfeeding, and ≥1 of the following conditions applies: 1.) Is not a WOCBP OR 2.) Is a WOCBP and using a study-approved contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle, during the treatment period and for at least 120 days after the last dose of study treatment.
– Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications within 1 week before randomization.
– Has adequate organ function.
Exclusion Criteria:
– Has known untreated central nervous system metastases and/or carcinomatous meningitis.
– Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for ≥3 years since initiation of that therapy. (Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.)
– Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
– Has had an allogeneic tissue/solid organ transplant.
– Has a known history of human immunodeficiency virus (HIV) infection.
– Has a history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
– Has a known history of hepatitis B or known active hepatitis C virus infection.
– Has a history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral study drug absorption.
– Has significant cardiovascular impairment within 12 months of the first dose of study treatment, such as a history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction, cerebrovascular accident/stroke, or cardiac arrhythmia associated with hemodynamic instability.
– Has not recovered adequately from any toxicity and/or complications from major surgery before starting study treatment.
– Has a known history of active tuberculosis (TB).
– Has an active infection requiring systemic therapy.
– Has previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity or intolerance to any component of lenvatinib or pembrolizumab.
– Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.
– Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC.
– Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily member 9 [CD137]) or has received lenvatinib as monotherapy or in combination with anti- programmed cell death protein (anti-PD-1) agents.
– Has received radiotherapy within 14 days before the first dose of study treatment or received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment. (Note: Participants must have recovered from all radiation-related toxicities to ≤Grade 1, not require corticosteroids, and not have had radiation pneumonitis.)
– Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days before the first dose of study treatment.
– Is receiving systemic steroid therapy (doses >10 mg daily of prednisone equivalent) within 7 days before the first dose of study treatment.
– Has received a live vaccine within 30 days before the first dose of study treatmen.
Study Contact:
Amy Feist
(952) 993-6071
Amy.Feist@ParkNicollet.com
NATALEE TRIO033 (NATALEE)
Principal Investigator: Rachel Lerner, MD
Study Sponsor: Novartis
Location: Frauenshuh Cancer Center
Phase of Study: Phase 3
Purpose of study: A phase III multi center, randomized, open label trial to evaluate efficacy and safety of ribociclib with endocrine therapy as adjuvant treatment in patients with HR+/HER2 – early breast cancer.
Inclusion Criteria:
– Patient is ≥ 18 years-old at the time of PICF signature
– Patient is female with known menopausal status at the time of PICF signature or initiation of adjuvant ET (whichever occurs earlier), or male.
– Patient with histologically confirmed unilateral primary invasive adenocarcinoma of the breast with a date of initial cytologic or histologic diagnosis within 18 months prior to randomization.
– Patient has breast cancer that is positive for ER and/or PgR
– Patient has HER2-negative breast cancer
– Patient has available archival tumor tissue from the surgical specimen
– Patient after surgical resection where tumor was removed completely, with the final surgical specimen microscopic margins free from tumor, and who belongs to one of the following categories (anatomic stage group II or III)
– If indicated, patient has completed adjuvant and/or neoadjuvant chemotherapy according to the institutional guidelines
– If indicated, patient has completed adjuvant radiotherapy according to the institutional guidelines
– Patient has no contraindication for the adjuvant ET in the trial and is planned to be treated with ET for 5 years
Exclusion Criteria:
– Patient has received any CDK4/6 inhibitor
– Patient has received prior treatment with tamoxifen, raloxifene or AIs for reduction in risk (“chemoprevention”) of breast cancer and/or treatment for osteoporosis within the last 2 years prior to PICF signature
– Patient has received prior treatment with anthracyclines at cumulative doses of 450 mg/m² or more for doxorubicin, or 900 mg/m² or more for epirubicin. Patient with a known hypersensitivity to any of the excipients of ribociclib and/or ET
– Patient with distant metastases of breast cancer beyond regional lymph nodes (stage IV according to AJCC 8th edition) and/or evidence of recurrence after curative surgery.
– Patient is concurrently using other anti-neoplastic therapy with the exception of adjuvant ET
– Patient has had major surgery, chemotherapy or radiotherapy within 14 days prior to randomization
– Patient has not recovered from clinical and laboratory acute toxicities related to prior anti-cancer therapies
– Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within 2 years before PICF signature
– Patient has known HIV infection, Hepatitis B or C infection
– Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality
– Patient is currently receiving any of the following substances within 7 days before randomization – Concomitant medications, herbal supplements, and/or fruits that are known as strong inhibitors or inducers of CYP3A4/5 or Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
– is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting trial treatment
– Patient has impairment of GI function or GI disease that may significantly alter the absorption of the oral trial treatments
– Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator’s judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol
– Patient participated in another interventional study and received treatment with an investigational product (or used an investigational device) within 30 days prior to randomization or within 5 half-lives of the investigational product, whichever is longer.
– Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial.
Study Contact:
Alissa Gavenda
(952) 993-6705
Alissa.Gavenda@ParkNicollet.com
NEKTAR PROPEL 16-214-05 A Phase 1b Open-Label, Multicenter Study to Investigate the Safety and Preliminary Efficacy of NKTR-214 in Combo with Anti-PD1 (Pembro) or Anti-PDL1 (Atezolizumab) in Patients with Locally Advanced or Metastatic Solid Tumors
Principal Investigator: Rachel Lerner, MD
Study Sponsor: Nektar Therapeutics
Location: Frauenshuh Cancer Center
Phase of Study: Phase 1
Purpose of Study:
To test the safety, tolerability, and effectiveness (how well these drugs work together) of NKTR-214 given in combination with pembrolizumab or atezolizumab. We want to find out what effects, good or bad, the study drug has on you and your cancer when combined with pembrolizumab or atezolizumab.
NTKR-214 is a modified (changed in the laboratory) form of a protein called interleukin-2 (or IL-2) which is normally made by your immune system. This protein is designed to trigger (wake up) other cells in your immune system to start attacking your cancer cells. IL-2 has been used for certain cancers for many years so doctors understand many of the risks and benefits.
Pembrolizumab and atezolizumab are prescription medicines used to treat locally advanced or metastatic (has spread into different areas of the body) melanoma, locally advanced or metastatic urothelial bladder cancer or metastatic Stage 4 Non-small cell lung cancer (IV-NSCLC). They are antibodies (known as checkpoint inhibitors) that block a type of protein (PD-1 or PD-L1) that can prevent human immune cells (called T cells) from attacking cancer cells. Pembrolizumab blocks PD-1, and atezolizumab blocks PD-L1.
Inclusion Criteria:
– Histologically confirmed locally advanced melanoma (pembrolizumab only), locally advanced or metastatic urothelial carcinoma, or metastatic NSCLC.
– Male or female patients, age 18 years or older at the time of signing the informed consent form (ICF).
– Life expectancy > 12 weeks as determined by the Investigator.
– Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
– Measurable disease per RECIST 1.1.
– Patients must not have received prior oncology regimens, including but not limited to inhibitors such as anti PD-1, anti-PD-L1, anti-PD-L2, anti CD137, or anti CTLA-4 (cytotoxic T lymphocyte-associated protein 4) antibody, or any other antibody or drug specifically targeting T cell co stimulation or checkpoint pathways, indoleamine 2,3-dioxygenase pathway inhibitors, cancer vaccines, adoptive cell therapies, or other cytokine therapies.
– MELANOMA patients: must have histologically confirmed stage III (unresectable) or stage IV melanoma, as per American Joint Committee on Cancer (AJCC) staging system
– MELANOMA patients: Ocular melanoma is excluded
– MELANOMA patients: Have not received prior anti-cancer therapy for advanced or metastatic melanoma
– MELANOMA patients: Patients with unknown BRAF mutation status may enroll so long as mutation testing is planned to be performed within 30 days of Cycle 1 Day 1
– NSCLC patients: Histologically confirmed or cytologically confirmed diagnosis of stage IV NSCLC
– NSCLC patients: First-line (pembrolizumab only), patients must have high PD-L1 expression (Tumor Proportion Score [TPS] ≥ 50%) as determined by FDA-approved test, with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
– NSCLC patients: Second-line (pembrolizumab or atezolizumab), patients must have experienced disease recurrence or progression during or after a prior platinum-based chemotherapy given for advanced or metastatic disease. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations and must not have received chemotherapy.
– If patient is to receive pembrolizumab in combination with NKTR 214, PD L1 expression by TPS should be ≥ 1% as determined by an FDA-approved test.
– UROTHELIAL CARCINOMA patients: Histologically or cytologically documented locally advanced or metastatic urothelial carcinoma
– UROTHELIAL CARCINOMA patients: First-line (pembrolizumab only), patients who are not eligible for cisplatin-containing chemotherapy.
– UROTHELIAL CARCINOMA patients: First-line (atezolizumab only), patients who have disease progression within 12 months of neoadjuvant or adjuvant treatment with chemotherapy.
– UROTHELIAL CARCINOMA patients: Second-line (pembrolizumab or atezolizumab), patients who have disease progression during or following platinum-containing chemotherapy.
– Additional criteria may apply.
Exclusion Criteria:
– Use of an investigational agent or an investigational device within 28 days before administration of first dose of study drug(s).
– Females who are pregnant or breastfeeding.
– Patients who have an active, known or suspected autoimmune disease. Patients requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents. (Exceptions include any patient on 10 mg or less of prednisone or equivalent, patients with vitiligo, hypothyroidism stable on hormone replacement, Type I diabetes, Graves’ disease, Hashimoto’s disease, alopecia areata, eczema, or with Medical Monitor approval).
– History of allergy or hypersensitivity to study drug components.
– Active malignancy not related to the current diagnosed malignancy.
– History of organ transplant that requires use of immune suppressive agents.
– Use of warfarin within 14 days of initiating study drug(s). (Note: Low molecular weight heparin is allowed on the study.)
– Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis.
– Prior surgery or radiotherapy within 14 days of initiating study drug(s). Patients must have recovered from all radiation-related toxicities, not required corticosteroids and have not had radiation pneumonitis.
– Additional criteria may apply
Study Contact:
Alissa Gavenda
(952) 993-6705
Alissa.Gavenda@ParkNicollet.com
POLARIS A5481082: Palbociclib in Hormone Receptor Positive Advanced Breast Cancer: A Prospective Multicenter Non-Interventional Study
Principal Investigator: Dan Anderson, MD
Study Sponsor: Pfizer, Inc.
Locations: Frauenshuh Cancer Center (Methodist Hospital); Regions Cancer Care Center (Regions Hospital)
Purpose of Study: To learn more about how palbociclib is used in routine clinical practice. The main goal of this non-interventional study is to describe and analyze the prescribing and treatment patterns of palbociclib in routine clinical practice. The study will collect and assess information related to how patients are treated by their doctor and it will collect information about patient experience. We will also collect additional information on the good and bad effects of the drug, palbociclib, which will be prescribed as part of routine cancer care. This study does not involve any changes to patients’ routine cancer care.
Inclusion Criteria:
– Age ≥18 years or older.
– Diagnosis of adenocarcinoma of the breast with evidence of metastatic disease or advanced disease not amenable to treatment with curative intent.
– Documented HR+ (ER+ and/or PR+) tumor based on local standards.
– Documented HER2- tumor based on local standards.
– Physician has determined that treatment with palbociclib is indicated.
– Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study
– Patients who in the opinion of the investigator are willing and able to comply with regular clinic visits as per standard of care practice at the site.
Exclusion Criteria:
– Patients with a life expectancy of less than 3 months at the time of ABC diagnosis, per the investigator’s judgment.
– Patients participating in any interventional clinical trial that includes investigational or marketed products at the time of enrollment. (Patients participating in other investigator initiated research or NIS can be included as long as their standard of care is not altered by the study).
– Patients on active treatment for malignancies other than ABC at the time of enrollment.
– Patients who are unable to understand the nature of the study and are unwilling to sign an informed consent.
Study Contact:
Jan Morgan
(952) 993-1737
Janet.Morgan@ParkNicollet.com
Please note that this study is not required to be listed on Clinicaltrials.gov. For more information, please contact the study coordinator listed above.
Phase II Study of Nivolumab and Ramucirumab for Patients with Previously-Treated Mesothelioma (LUN 15-299)
Principal Investigator: Arek Dudek, MD, PhD
Study Sponsor: Hoosier Cancer Research Network
Location: Regions Cancer Care Center
Phase of Study: Phase 2
Purpose of Study:
To assess whether the combination of immunotherapy and a drug that works to block the formation of new cancer blood vessels will stop the growth of mesothelioma. The current standard treatment for mesothelioma it to receive pemetrexed with a platinum-based chemotherapy. However, there is currently no standard treatment once pemetrexed in combination with a platinum-based chemotherapy is no longer working. People who are not in a study are usually treated with a different type of chemotherapy (vinorelbine, gemcitabine, or paclitaxel), immunotherapy, or with a drug that works to block the formation of new cancer blood vessels.
The immune system functions to protect your body against “foreign” invaders such as cancer by making special cells called T-cells. Over time cancer cells have developed a way to hide or camouflage themselves from the immune system by expressing a protein on their surface called PD-L1. When PD-L1 on the cancer cells binds to PD-1 on your immune system’s T-cells the immune system is turned off and no longer works to attack cancer cells. Nivolumab is an immunotherapy drug that works by blocking PD-1 receptor on T-cells from being able to bind PD-L1 released by cancer cells. This allows your immune system’s T-cells to recognize cancer cells as “foreign” and continue to attack the cancer cells.
Cancer, including mesothelioma, needs to make new blood vessels in order to survive and grow. People with advanced mesothelioma who are not in a study are sometimes treated with a class of drugs that block the formation of new blood vessels. These drugs are termed anti-angiogenic drugs. Two drugs in this class of medications are called bevacizumab and ramucirumab. Bevacizumab has been studied in mesothelioma, while ramucirumab has not.
Inclusion Criteria:
– Histologically-confirmed malignant mesothelioma not amenable to curative surgery and who have received at least one pemetrexed-containing chemotherapy regimen.
– Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
– Adequate blood counts and renal, bone marrow, and hepatic function
– Subjects on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin (LMWH). Patients receiving warfarin must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy. For heparin and LMWH there should be no active bleeding (that is, no bleeding within 14 days prior to first dose of protocol therapy) or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices).
– Women of childbearing potential (WOCP) must be willing to use two methods of birth control. WOCP should begin using birth control from the screening visit, throughout the study period, and up to 161 days (about 5 months) following the last dose of study drugs.
– Men who are not surgically or medically sterile must agree to use an acceptable method of contraception. Male subjects with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must agree to use condoms with spermicide from the date of the first dose of study drug, throughout the study period, and through at least 217 days (about 7 months) after the last dose of study drug. Total abstinence for the same study period is an acceptable alternative.
– Measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to modified RECIST 1.1 criteria, and obtained by imaging within 28 days prior to study registration.
– Prior intra-cavity cytotoxic or sclerosing agents (including bleomycin) is acceptable.
– Radiation therapy must be completed > 28 days before study registration, and the measurable disease must be outside of the radiation port.
– Pemetrexed-containing chemotherapy must be completed > 28 days before study registration.
– All previous toxicity resolved to Grade 1 or less.
Exclusion Criteria:
– Any Grade 3-4 GI bleeding within 3 months prior to study registration.
– History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered “significant”) during the 3 months prior to study registration.
– Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to study registration.
– Cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis (any degree) with a history of hepatic encephalopathy, or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
– Uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management.
– Prior history of GI perforation/fistula (within 6 months of study registration) or risk factors for perforation.
– Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to study registration.
– Active brain metastases or carcinomatous meningitis.
– Major surgery within 28 days prior to study registration
– Subcutaneous venous access device placement within 7 days prior to study registration.
– Elective or planned major surgery to be performed during the course of the clinical trial.
– Is receiving chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted.
– Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: HIV testing is not required.
– Known history of testing positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody), indicating acute or chronic infection. NOTE: Hepatitis B and Hepatitis C testing is not required.
– Condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
– Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
– Received a live vaccine within 30 days prior to the first dose of trial treatment.
– History of interstitial lung disease or active, non-infectious pneumonitis.
– Female subject is pregnant or breast-feeding.
– Major blood vessel invasion or significant intratumor cavitation.
– If they experience hemoptysis (defined as bright red blood or ≥ ½ teaspoon) within 2 months prior to first dose of protocol therapy or with radiographic evidence of intratumor cavitation or has radiologically documented evidence of major blood vessel invasion or encasement by cancer.
– Any condition that, in the opinion of the investigator, might jeopardize the safety of the subject or interfere with protocol compliance.
– Any mental or medical condition that prevents the subject from giving informed consent or participating in the trial.
– Any pathological condition that carries a high risk of bleeding (for example, tumor involving major vessels or known varices.)
– Known hypersensitivity to nivolumab or ramucirumab or any of their components.
– Known history of active tuberculosis.
– Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
– No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason ≤ grade 7 prostate cancers, or other cancer for which the subject has been disease-free for at least 5 years.
– Treatment with any investigational agent within 28 days prior to study registration. The subject must have recovered from the acute toxic effects of the regimen.
Study Contact:
Lisa Wahowske, RN, BSN, OCN
(651) 254-1517
Lisa.Wahowske@ParkNicollet.com
Randomized Phase II Trial of single agent chemotherapy plus Nivolumab or single Agent Chemotherapy Alone in Patients with Advanced Squamous or Non-squamous NSCLC with Primary Resistance to Prior PD-1 or PD-L1 Inhibitor (LUN 15-233)
Principal Investigator: Arek Dudek, MD, PhD
Study Sponsor: Hoosier Cancer Research Network
Location: Regions Cancer Care Center
Phase of Study: Phase 2
Purpose of Study:
To assess whether using nivolumab plus single agent chemotherapy together is better at controlling cancer than using single agent chemotherapy itself.
Your immune system sends out special cells called T cells to fight infections and diseases throughout your body. Some cancer cells can hide from T cells by taking control of a pathway called PD-1. This lets the cancer cells avoid an attack from T cells. Certain immunotherapy medications can block the PD-1 pathway. By blocking PD-1, it allows the human immune system to recognize and kill cancer cells.
Nivolumab (also known as Opdivo®) is approved by the Food and Drug Administration (FDA) in the United States for the treatment of several cancers. Taxotere, pemetrexed and gemcitabine are standard chemotherapy medications for patients who progress during treatment with nivolumab (or other immunotherapy medications).
While nivolumab and single agent chemotherapy are approved by the FDA in certain settings, continuing to give nivolumab after progression combined with single agent chemotherapy should be considered “investigational.” This means using these drugs in this setting has not been approved by the FDA.
Inclusion Criteria:
– Age ≥ 18 years at the time of consent.
– ECOG Performance Status of 0-2 within 28 days prior to randomization.
– Histological or cytological confirmed squamous or non-squamous non-small cell lung cancer.
– Measurable disease according to RECIST 1.1 within 28 days prior to randomization.
– A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to randomization, have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic.
– Subjects must have primary resistance to PD-1 or PDL-1 inhibitors; defined as PD after 3 or fewer treatments with a PD-1 or PDL-1 inhibitor
– Subjects must have progressed on or after previous platinum-based chemotherapy. Chemotherapy may have previously been given with a PD-1 or PD-L1 inhibitor. Subjects must have also progressed on or after receiving any PD-1 or PD-L1 inhibitor (including nivolumab) as their most recent therapy.
– Most recent PD-1 or PD-L1 inhibitor infusion must be completed at least 6 weeks of randomization. The subject must have recovered from all reversible acute toxic effects (other than alopecia) to ≤ Grade 1 or baseline.
– Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to randomization.
– Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 14 days prior to registration. These women must also have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of Nivolumab then every 6 weeks thereafter.
– Women of childbearing potential must be willing to abstain from heterosexual activity or use an effective method of contraception from the time of informed consent until 5 months after treatment discontinuation. Women cannot breast feed from the time of informed consent to 5 months after last dose of study treatment. See below for adequate methods of contraception.
– Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving Nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. See below for methods of contraception.
– As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
Exclusion Criteria:
– Prior treatment with the single agent chemotherapy the site investigator chooses to use for this protocol (pemetrexed, taxotere or gemcitabine).
– Previous autoimmune complication from PD-1 or PD-L1 requiring discontinuation of therapy or treatment with steroids (ongoing treatment with more than 10 mg of prednisone or steroid equivalent daily, excluding inhaled or topical steroids).
– Previous discontinuation from PD-1 or PD-L1 due to an adverse event.
– Any serious or uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy.
– Pregnant or breastfeeding
– Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
– Active central nervous system (CNS) metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for [lowest minimum is 4 weeks or more] after treatment is complete and within 28 days prior to the first dose of Nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
– Treatment with any investigational drug within 30 days prior to registration.
– Subjects whose tumors express EGFR mutations on exons 19 and 21, ALK rearrangement, or ROS1 rearrangement who still have other FDA approved targeted agents available for treatment.
– Subjects with an active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids/immunosuppressive medications EXCEPT for syndromes which would not be expected to recur in the absence of an external trigger. (Subjects with vitiligo, autoimmune thyroiditis, or type I diabetes mellitus are permitted to enroll.)
– As there is potential for hepatic toxicity with Nivolumab, drugs with a predisposition to hepatoxicity should be used with caution in subjects treated with Nivolumab-containing regimen.
– Subjects should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
– Subjects should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
– History of allergy to study drug components.
– Prior solid organ or stem cell transplant
Study Contact:
Lisa Wahowske, RN, BSN, OCN
(651) 254-1517
Lisa.Wahowske@ParkNicollet.com
STM-03: Phase 1 Study of Procaspase Activating Compound-2 (PAC-1) in the Treatment of Advanced Malignancies (Component 2)
Principal Investigator: Richard Peterson, MD
Study Sponsor: Vanquish Oncology
Location: Regions Cancer Care Center (Regions Hospital)
Phase of Study: Phase 1
Purpose of Study: To find the highest and safest dose of an experimental drug in combination with the chemotherapeutic agent, temozolomide (Temodar®) by evaluating the safety (side effects) of the treatment combination in patients with glioblastoma multiforme.
PAC-1 is an investigational drug. PAC-1 is only available by participating in a research study. Since using PAC-1 in humans is new and is considered investigational, we have obtained permission from the Food and Drug Administration to conduct this study. Temozolomide is approved by the Food and Drug Administration for the treatment of recurrent malignant glioma (brain cancer) after unsuccessful chemotherapy treatment with other agents (either because of lack of efficacy or because of side effects).
Some cancers, including the one that you have, have an overabundance of an enzyme called procaspase-3 in the cells that make up your tumor. Cancer cell death does not occur because procaspase-3 is not activated into another enzyme, caspase-3, which is critical for programmed cell death, or apoptosis. PAC-1 is a drug that activates procaspase-3 to caspase-3, resulting in programmed cancer cell death. PAC-1 has been tested in animals and has slowed down the growth of tumors. Temozolomide, the other drug you will receive in this study, exhibits anticancer activity by interfering with DNA replication of cancer cells. PAC-1 exhibits anticancer activity by promoting the death of cancer cells. Using the combination of two drugs that affect cancer cells in different ways theoretically attacks the cancer cells from two different approaches.
Inclusion Criteria:
– Male or female ≥ 18 years of age
– Diagnosis of high grade glioma: glioblastoma multiforme (GBM) or anaplastic astrocytoma after progression following treatment with standard first line therapy
– Has measurable disease per RANO criteria
– Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
– Has adequate hepatic, renal and bone marrow function
– Patients taking antiepileptic drugs (AED) must be on stable doses of AED for at least two weeks prior to registration and have no episode of seizures for at least 14 days prior to registration. Because some AEDs enhance or inhibit enzymes that may affect PAC-1 metabolism, those AEDs will not be permitted in this study.
– Other inclusion criteria may apply. Please click on the “View Study Link” below for a complete list of inclusion criteria.
Exclusion Criteria:
– Had surgery within 4 weeks prior to study treatment except for minor procedures (hepatic biliary stent placement is allowed)
– Patients may not have received cytotoxic chemotherapy, targeted therapies, biologic response modifiers, chemotherapy, and hormonal therapy within the last 3 weeks, or nitrosureas within the last 6 weeks prior to study treatment.
– Has a known hypersensitivity to temozolomide
– Has a history of blood clots, pulmonary embolism, or deep vein thrombosis unless controlled by anticoagulant treatment (patient must be on stable dose for 2 weeks)
– Has a history of an arterial thromboembolic event within the prior six months including cerebrovascular accident, transient ischemic attack, myocardial infarction, or unstable angina.
– Other exclusion criteria may apply. Please click on the “View Study Link” below for a complete list of inclusion criteria.
Study Contact:
Lisa Wahowske, RN, BSN, OCN
(651) 254-1517
Lisa.Wahowske@ParkNicollet.com
Seattle Genetics SGNTV – 01
Principal Investigator: Daniel Anderson, MD
Study sponsor: Seattle Genetics
Location: Frauenshuh Cancer Center
Phase of Study: Phase 2
Purpose of study: The primary goal of this global, open label, multicenter trial is to assess the activity, safety, and tolerability of tisotumab vedotin for the treatment of selected solid tumors. Patients will be treated with single agent tisotumab vedotin every three weeks. Patients who meet eligibility criteria will be enrolled into one of 4 cohorts of tumor types known to express Tissue Factor. These include colorectal cancer, squamous non-small cell lung cancer (NSCLC), exocrine pancreatic adenocarcinoma, and squamous cell carcinoma of the head and neck (SCCHN).
Inclusion Criteria:
-Relapsed, locally-advanced or metastatic colorectal or pancreatic cancer, squamous NSCLC, or SCCHN patients who are not candidates for standard therapy.
-All patients must have experienced disease progression on or after their most recent systemic therapy.
-Baseline measurable disease as measured by RECIST v1. 1.
-Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
-Colorectal cancer patients must have received prior therapy with each of following agents, if eligible: a fluoropyrimidine, oxaliplatin, irinotecean, and/or bevacizumab. Patients should have received no more than 3 systemic regimens in the metastatic setting.
-Patients with NSCLC must have predominant squamous histology. Patients must have received prior therapy with a platinum-based treatment, a tyrosine kinase inhibitor, and a checkpoint inhibitor (CPI), if eligible. Patients should have received no more than 2 systemic regimens in the locally advanced or metastatic setting.
-Patients with exocrine pancreatic adenocarcinoma must have predominant adenocarcinoma histology. Patients must have received prior therapy with a gemcitabine-based or 5FU-based regimen, if eligible, and should have received no more than 1 systemic regimen in the unresectable or metastatic setting.
-Patients with SCCHN must have received prior therapy with a platinum-based regimen and a checkpoint inhibitor (CPI), if eligible, and should have received no more than 2 systemic regimens in the recurrent/metastatic setting.
Exclusion Criteria:
-Active bleeding conditions
-Ocular surface disease at the time of enrollment
-Pulmonary disease requiring chronic medical therapy, unrelated to underlying cancer
-Uncontrolled tumor-related pain
-Peripheral neuropathy greater than or equal to Grade 2
-History of another malignancy within 3 years of the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy.
-Active or previous brain metastasis
-Patients who are breastfeeding, pregnant, or planning to become pregnant from the time of informed consent until 6 months after the final study dose is administered
-For patients with SCCHN or NSCLC, ongoing anticoagulant therapy
Study Contact:
Alissa Gavenda
(952) 993-6705
Alissa.Gavenda@ParkNicollet.com
TAK 981-1002: An Open Label, Dose-Escalation, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics, of TAK-981 in Adult Patients with Metastatic Solid Tumors or Lympho-mas (TAK 981-1002)
Principal Investigator: Arkadiusz Dudek, PhD, MD
Study Sponsor: Takeda Pharmaceuticals
Location: Regions Cancer Care Center
Phase of Study: Phase 1
Purpose of Study: The purpose of this study is to evaluate safety, tolerability and to identify the most appropriate dose of TAK-981 as treatment for patients with cancer. In addition, this study will also serve to obtain information on the amount of study drug in your blood after taking single and/or multiple doses of the study drug.
The main purposes of this study are:
– To determine if TAK-981 is safe in patients with cancer.
– To select the dose for future studies.
– To measure the amount of TAK-981 in your blood.
– To assess the anti-tumor effect of TAK-981.
– To assess how the research drug reaches its target protein (called SUMO activating enzyme). Small Ubiquitin-like
Modifier (or SUMO) proteins are proteins that attach and detach from other proteins. This happens in normal and
tumor cells to modify their function. SUMOylation is the process of adding these SUMO proteins to other proteins.
The process of SUMOylation allows growth of tumor cells, and prevents the immune system from attacking the
tumor. TAK-981 reduces SUMOylation, allowing the immune system to attack the tumor cells.
– To obtain information on how your body reacts to the study drug by looking at biomarkers. Biomarkers are
measurable substances that can be found in different tissues of your body like the blood, skin and the tumor.
– To determine if the amount of TAK-981 in your blood has any impact on your ECG results (heart function test).
TAK-981 is an investigational drug that has not yet been studied in humans. It has not been approved by the FDA (U.S. Food and Drug Administration) or other regulatory authorities for use by the general public. TAK-981 will be investigated in adult patients with metastatic solid tumors or lymphomas for which standard curative treatment or life-prolonging treatment does not exist, is no longer effective or if it cannot be tolerated or is not indicated for you.
Inclusion Criteria:
– Adult male or female patients ≥18 years old.
– Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
– Patients with histologically confirmed advanced (local regionally recurrent not amenable to curative therapy) or
metastatic solid tumors that have no standard therapeutic option with a proven clinical benefit, are intolerant or have
refused them, OR Patients with relapsed/refractory lymphoma not amenable to therapies with proven clinical benefit or
who are intolerant or who refuse them. Patients with low-grade lymphomas such as follicular lymphoma, small
lymphocytic lymphoma, lymphoplasmacytoid lymphoma, and marginal zone lymphomas may not need to exhaust all
available therapy. These patients can be enrolled after failure of at least 2 prior systemic therapies, provided that
there is not an immediate need for cytoreduction. In these cases, patients who need immediate therapy for tumor bulk
are not eligible for this trial.
– Adequate bone marrow reserve and renal and hepatic function
– Left ventricular ejection fraction (LVEF) ≥40%; as measured by echocardiogram or MUGA scan.
– Recovered to Grade 1, baseline or established as sequela, from all toxic effects of previous therapy (except alopecia,
neuropathy, or autoimmune endocrinopathies with stable endocrine replacement therapy).
Exclusion Criteria:
– Treatment with systemic anticancer treatments or investigational products within 14 days before the first dose of
study drug or 5 half-lives, whichever is shorter. Patients should have recovered from previous treatment toxicity to
Grade 1, baseline (except alopecia and peripheral neuropathy), or the toxicity is considered established as a
sequela.
– History of uncontrolled brain metastasis. Patients with brain metastases are allowed if they are previously treated with
surgery, whole-brain radiation, or stereotactic radiosurgery and the patients is receiving a corticosteroid dose ≤10
mg/day of prednisone equivalent at the time of receiving the first dose of TAK-981. For asymptomatic patients,
screening brain imaging is not required.
– Patient has received extended field radiotherapy ≤4 weeks before the start of treatment (≤2 weeks for limited field
radiation for palliation), and who has not recovered to grade 1 or better from related side effects of such therapy
(except for alopecia).
– Patient is receiving any live vaccine (eg, varicella, pneumococcus) within 4 weeks of initiation of study treatment.
– History of any of the following ≤6 months before first dose: congestive heart failure New York Heart Association Grade
III or IV, unstable angina, myocardial infarction, unstable symptomatic ischemic heart disease, uncontrolled
hypertension despite appropriate medical therapy, ongoing symptomatic cardiac arrhythmias of >Grade 2, pulmonary
embolism, or symptomatic cerebrovascular events, or any other serious cardiac condition (eg, pericardial effusion or
restrictive cardiomyopathy). Chronic atrial fibrillation on stable anticoagulant therapy is allowed.
– Baseline prolongation of the QTc interval (eg, repeated demonstration of QTc interval >480 ms, history of congenital
long QT syndrome, or torsades de pointes).
– Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase
the risk of AEs or has compromised ability to provide written informed consent.
– Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.
Study Contact:
Lisa Wahowske, RN, BSN, OCN
(651) 254-1517
Lisa.Wahowske@ParkNicollet.com
TTC-352-101: Phase 1 Study of TTC-352 in Patients with Metastatic Breast Cancer Progressing on Endocrine Therapy
Principal Investigator: Randy Hurley, MD
Study Sponsor: TTC Oncology
Location: Regions Cancer Care Center (Regions Hospital)
Phase of Study: Phase 1
Purpose of Study: To find the highest and safest dose (maximum tolerated dose or MTD) of TTC‑352, an experimental drug, in patients with metastatic, estrogen receptor positive breast cancer that has continued to progress (worsen) despite treatment with standard hormonal therapy.
TTC-352 is an investigational drug. TTC-352 is only available by participating in a research study. Since using TTC-352 in humans is new and is considered investigational, we have obtained permission from the Food and Drug Administration to conduct this study.
You have breast cancer tissue that is positive for the estrogen (hormone) receptor. Estrogen binds to the estrogen receptor and promotes tumor growth. Patients such as yours typically undergo hormone therapy as the initial treatment option. However, many patients, including you, have developed resistance to this treatment (that is, the drug stops working and the tumor grows). TTC-352 is a small molecule that, in two animal models of treatment resistant-breast cancer, caused complete tumor regression that persisted after the drug was no longer given. TTC-352 comes from the class of drugs called selective estrogen mimics, or SEMs. The manner by which SEMS are thought to work is that they attach to the estrogen receptor and thus block estrogen from attaching to the receptor. This slows or stops the growth of the tumor by preventing the cancer cells from getting the hormones they need to grow.
Inclusion Criteria:
– be ≥18 years of age;
– have a diagnosis of metastatic ER+ breast cancer in patients who received and progressed on at least two lines of endocrine therapy, with one that included a CDK4/CDK6 inhibitor (e.g., palbociclib or ribociclib);
– have metastatic disease evaluable on imaging studies;
– have a histologically confirmed diagnosis of ER+ breast cancer;
– have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 (Appendix II);
– have adequate hepatic function, defined as having a serum total bilirubin concentration ≤1.5mg/d, or ≤2 x the upper limit of normal (ULN) if associated with hepatobiliary metastases or Gilbert syndrome, and having serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations ≤2.5 × ULN, or ≤5 x ULN for patients with known hepatic metastases;
– have adequate renal function, defined as having a serum creatinine ≤1.5 × ULN and a creatinine clearance ≥40mL/min (estimated using the Cockcroft-Gault formula);
– have adequate hematologic function, defined as having a hemoglobin ≥8g/dL, an absolute neutrophil count (ANC) ≥1.0 × 109/L, and platelet count ≥75.0 x 109/L;
– be willing and able to comply with study visits and procedures;
– have read, understood and signed the informed consent form (ICF) approved by the Institutional Review Board (IRB);
– if a woman of childbearing potential (WOCP), not be pregnant (confirmed by a negative serum pregnancy test within 14 days of study entry and re-confirmed by a urine pregnancy test on the morning of Study Day 1, prior to the start of study treatment) and/or not be breast-feeding; [Note: Women who are postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) are not considered to be a WOCP.]
– If a WOCP, agree to use during the study and for at least one month after the last dose of study drug a medically acceptable method of birth control [such as an oral, implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device (IUD), a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence.];
– if male (and whether or not surgically or medically sterile), agree to use during the study and for at least one month after the last dose of study drug a double barrier method of birth control (in addition to any other birth control method practiced by his partner) while engaging in sexual intercourse with a partner who is pregnant, possibly pregnant or able to become pregnant.
Exclusion Criteria:
– have received chemotherapy, hormonal therapy, biologic therapy, immunotherapy or radiation therapy within 14 days prior to the planned start of study treatment.
– have inadequate recovery* from adverse events resulting from previously-administered anti-cancer therapies; [*Note: Unless more specifically defined in Inclusion Criteria 6, 7 and 8 above, adequate recovery is defined as -improvement to ≤ Grade 2 for any other hematologic toxicity and for peripheral neuropathy, and improvement to ≤ Grade 1 for any other non-hematologic toxicity.]
– have a history of venous thromboembolism, including deep vein thrombosis, pulmonary embolism or retinal vein thrombosis, unless currently on anticoagulant therapy;
– have impending visceral crisis that requires chemotherapy;
– have known uncontrolled or symptomatic CNS metastases;
– have any clinically significant infection, defined as any acute viral, bacterial, or fungal infection that requires systemic treatment or have received any anti-infective treatment within 7 days prior to the screening visit;
– have any other severe, uncontrolled medical condition, including unstable congestive heart failure (Stage III-IV of the New York Heart Association Functional Classification (Appendix III))
– have a known or suspected allergy to the study drug or any study drug component;
– have any other medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation, that may interfere with the interpretation of study results or that otherwise would, in the opinion of the Investigator, make study participation inappropriate;
– have any non-healing wound, fracture, or ulcer within 28 days prior to the planned start of study treatment;
– have received any other investigational drug within 28 days (or 5 half-lives, if longer) prior to the start of study screening.
Study Contact:
Lisa Wahowske
(651) 254-1517
Lisa.Wahowske@ParkNicollet.com
