Radiation Therapy and Durvalumab, With or Without Tremelimumab, in Patients With Bladder Cancer

Withdrawn before enrolling · Phase 2

Conditions studied: Bladder Cancer

In brief

This is a multi-site, randomized, prospective, open-label phase II study. Patients in this study will have localized (cT3-cT4), or metastatic bladder cancer with a symptomatic, intact primary bladder tumor. In this study, patients will undergo stereotactic body radiation therapy (SBRT) to the bladder tumor and will receive durvalumab with or without tremelimumab.

Key facts

Study ID

NCT03150836

Run by

Terence Friedlander, MD

People needed

0

Starts

2017-10-01

Expected to finish

2024-09-01

Last updated by the study team

2017-10-19

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Written informed consent obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations
• Locally advanced (cT3 or cT4) or metastatic (N+ or M+) urothelial bladder cancer. Mixed histologies with predominant urothelial pattern are allowed
• If metastatic disease present patients must have an intact, symptomatic bladder tumor, appropriate for palliative RT to the bladder.
• Measurable metastatic disease according to RECIST v1.1 criteria. Thus, patients with metastatic disease must have at least 1 lesion, not previously irradiated, that can be accurately measured at baseline as at least 10 mm in the longest diameter (except lymph nodes which must have a short axis greater than or equal to 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurement as per RECIST v1.1 guidelines.
• Age greater than or equal to 18 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Life expectancy of at least 12 weeks
• Patients with non-metastatic bladder cancer must be ineligible for cystectomy in the opinion of the treating investigator.
• Patients must be ineligible for cisplatin-based chemotherapy. The reason for cisplatin ineligibility must be documented. Cisplatin ineligibility is defined as meeting 1 of the following criteria:
• Creatinine clearance (calculated or measured) less than 60 mL/min
• Common Terminology Criteria for Adverse Events (CTCAE) Grade greater than or equal to 2 audiometric hearing loss
• CTCAE Grade 2 or higher peripheral neuropathy
• New York Heart Association Class III heart failure
• Any other criteria deemed by the investigator to make the patient unsuitable for cisplatin-based chemotherapy.
• Subjects must consent to provide an archived tumor specimen from within 12 months prior to study entry (ie, from subject signing consent to participate in the study) for immunologic characterization. If not available, subjects should have at least 1 lesion amenable to biopsy and consent to provide a pre-treatment fresh biopsy. Tumor lesions used for biopsy should not be lesions used as target lesions. Additional archival tissue from beyond 12 months prior to study entry is also requested, if available, to support exploratory analyses.
• Adequate normal organ and marrow function as defined below:
• Hemoglobin greater than or equal to 9.0 g/dL
• Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L (greater than 1500 per mm3)
• Platelet count greater than or equal to 100 x 109/L (greater than100,000 per mm3)
• Serum bilirubin less than or equal to 1.5 x institutional upper limit of normal (ULN). [This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician].
• AST (SGOT)/ALT (SGPT) less than or equal to 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be less than or equal to 5x ULN.
• Serum creatinine CL greater than 30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance. Serum creatine measurement is the preferred measurement for determining creatinine clearance.
• Males:
• Creatinine CL (mL/min) = [Weight (kg) x (140 - Age)] / [72 x serum creatinine (mg/dL)]
• Females:

You may not qualify if…

• ECOG PS 2 or higher
• Upper tract-only or urethral-only urothelial cancer
• Prior cystectomy or definitive RT to the bladder.
• Prior systemic chemotherapy for bladder cancer
• 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 antiphospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
• Subjects with childhood atopy or asthma, vitiligo, alopecia, Hashimoto syndrome, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are not excluded.
• Patients with controlled type 1 diabetes mellitus on a stable dose of insulin regimen are not excluded.
• Any chronic skin condition that does not require systemic therapy are not exluded
• Patients without active autoimmune disease in the last 5 years may be included after consultation with the study physician.
• Patients with HIV, active hepatitis B (HBV) or active hepatitis C (HCV)
• Patients with past HBV infection or resolved HBV infection, defined as the presence of hepatitis B core antibody (HBc Ab) and absence of hepatitis B surface antigen (HBsAg) are eligible. HBV DNA must be obtained in these patients prior to day 1 of therapy, but detection of HBV DNA in these patients will not exclude study participation.
• Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• 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.
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Previous IP assignment in the present study
• Current enrollment/participation in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study.
• Prior exposure to immune-mediated therapy, including but not limited to, durvalumab, tremelimumab, other anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, and therapeutic anticancer vaccines. Prior BCG or intravestical immune therapy (ie interferon) is not an exclusion to study participation.
• Prior radiation therapy to the abdomen or pelvis.
• Any concurrent systemic chemotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (i.e. hormonal replacement therapy) is acceptable.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note biopsy and TURBT of the primary tumor is acceptable.
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease for at least 5 years before the first dose of study drug and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease

Where it is running

• UCSF Helen Diller Family Comprehensive Cancer Center — San Francisco, California, United States

Full record on ClinicalTrials.gov

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