Overview

A Study of Atezolizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer (Cohort 1)

Status:
Active, not recruiting
Trial end date:
2022-03-02
Target enrollment:
0
Participant gender:
All
Summary
This Phase II, single-arm study is designed to evaluate the effect of atezolizumab treatment in participants with locally advanced or metastatic urothelial bladder cancer. Participants will be enrolled into 1 of 2 cohorts. Cohort 1 (reported here) will consist of participants who are treatment-naïve and ineligible for cisplatin-containing chemotherapy. Cohort 2 will contain participants who have progressed during or following a prior platinum-based chemotherapy regimen. The results of the second cohort are reported separately (NCT02108652). Participants in both cohorts will be given a 1200 milligrams (mg) intravenous (IV) dose of atezolizumab on Day 1 of 21-day cycles. Treatment of participants in Cohort 1 will continue until disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or unmanageable toxicity. Treatment of participants in Cohort 2 will continue until loss of clinical benefit or unmanageable toxicity.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Hoffmann-La Roche
Treatments:
Antibodies, Monoclonal
Atezolizumab
Criteria
Inclusion Criteria:

- Histologically or cytologically documented locally advanced or metastatic transitional
cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder,
urethra)

- Representative tumor specimens as specified by the protocol

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Life expectancy greater than or equal to (>=) 12 weeks

- Measurable disease, as defined by RECIST v1.1

- Adequate hematologic and end organ function

Cohort 1-Specific Inclusion Criteria

- No prior chemotherapy for inoperable locally advanced or metastatic or recurrent
urothelial carcinoma

- Ineligible for cisplatin-based chemotherapy due to one of the following: Impaired
renal function, a hearing loss of 25 decibels (dB) at two contiguous frequencies,
Grade 2 or greater peripheral neuropathy, or ECOG performance score of 2

Exclusion Criteria:

- Any approved anti-cancer 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 central nervous system (CNS) metastases as determined by computed
tomography (CT) or magnetic resonance imaging (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)

- Uncontrolled hypercalcemia (greater than [>] 1.5 millimoles per liter [mmol/L] ionized
calcium or Ca > 12 milligrams per deciliter [mg/dL] or corrected serum calcium > upper
limits of normal [ULN]) or symptomatic hypercalcemia requiring continued use of
bisphosphonate therapy or denosumab

- Malignancies other than urothelial bladder 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 or incidental prostate cancer

- Pregnant and lactating women

- History of autoimmune disease

- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest CT scan

- Serum albumin less than (<) 2.5 grams per deciliter (g/dL)

- Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or
hepatitis C or tuberculosis

- Severe infections within 4 weeks prior to Cycle 1, Day 1

- Significant cardiovascular disease

- Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day
1

- Prior allogeneic stem cell or solid organ transplant

- Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1

- 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 patient at high risk from treatment
complications

- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including
anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4), anti-programmed
death-1 receptor (anti-PD-1), and anti-programmed death-ligand 1 (anti-PD-L1)
therapeutic antibodies