A Phase II Trial of Atezolizumab and Bevacizumab in Cisplatin-ineligible Subjects with Advanced/Unresectable Urothelial Cancer (GU15-215)
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:
The purpose of this study is to evaluate any good and bad effects of treating your different types of urothelial cancer with atezolizumab plus bevacizumab. Atezolizumab is already an FDA approved treatment for advanced urothelial cancer for people who cannot safely receive cisplatin chemotherapy, and this study will assess the effect (good or bad) of adding bevacizumab to atezolizumab. Bevacizumab is not FDA approved standard treatment for urothelial cell carcinoma. In this study, you will receive 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.
– Age ≥ 18 years.
– ECOG Performance Status 0, 1 or 2 within 28 days prior to randomization.
– Histologic or cytological evidence of 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.
– Willing to undergo a core needle or excisional biopsy on-treatment.
– Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment.
– Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment.
– Active or untreated CNS metastases as determined by CT or MRI evaluation during screening and prior radiographic assessments.
– Leptomeningeal disease.
– Uncontrolled tumor-related pain.
– Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
Lisa Wahowske, RN, BSN, OCN
AB928CSP002: A Phase I/Ib Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants with Breast and Gynecologic Malignancies (AB928CSP002)
Principal Investigator: Arkadiusz Dudek, MD, PhD
Study sponsor: Arcus Biosciences, Inc.
Locations: Regions Cancer Care Center
Phase of Study: Phase 1
Purpose of study: This study will help us understand whether a potential new treatment, AB928, can be safely given in combination with chemotherapy to subjects with cancer. AB928 will be evaluated in combination with a chemotherapy treatment Pegylated liposomal doxorubicin (PLD) or nanoparticle albumin-bound (nab)- paclitaxel (NP) with or without another experimental drug called IPI-549. AB928 and IPI-549 are considered investigational and are not approved by the U.S Food and Drug Administration (FDA).
– Female participants ≥ 18 years of age at the time of screening.
– Women with no childbearing potential because of surgery or at least 1 year post-menopause, or menopause confirmed by follicle-stimulating hormone testing.
– Must have at least 1 measurable lesion per RECIST v1.1.
– ECOG performance status score of 0 or 1.
– Must have archival tissue sample available for donation.
– Use of any live vaccines against infectious diseases within 4 weeks (28 days) of initiation of investigational product.
– Underlying medical conditions that, in the Investigator’s or Sponsor’s opinion, will make the administration of investigational product hazardous (eg, interstitial lung disease, active infections requiring antibiotics, recent hospitalization with unresolved symptoms) or obscure the interpretation of toxicity determination or AEs, or concurrent medical condition requiring the use of immunosuppressive medications or immunosuppressive doses of systemic or absorbable topical corticosteroids.
– Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
– Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 30 days after the last dose of investigational product regimen.
– Baseline QT interval corrected with Fridericia’s method (QTcF) > 480 ms (average of triplicate readings).
Lisa Wahowske, RN BSN, OCN
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.
– 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.
– 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
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.
– Adult male of female patients >/= 18 years old.
– Eastern Cooperative 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.
– Adequate bone marrow reserve and renal and hepatic function.
– 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.
Lisa Wahowske, RN, BSN, OCN