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.
– 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
– 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
Lisa Wahowske, RN, BSN, OCN