Overview

This trial is active, not recruiting.

Condition bladder cancer
Treatments atezolizumab (mpdl3280a) [tecentriq], an engineered anti-pdl1 antibody, docetaxel, paclitaxel, vinflunine
Phase phase 3
Target PD-1
Sponsor Hoffmann-La Roche
Start date January 2015
End date November 2017
Trial size 932 participants
Trial identifier NCT02302807, 2014-003231-19, GO29294

Summary

This is a Phase III, global, multicenter, open-label, two-arm, randomized, controlled study designed to evaluate the efficacy and safety of atezolizumab compared with chemotherapy in participants with locally advanced or metastatic urothelial bladder cancer (UBC) who have progressed during or following a platinum-containing regimen. The anticipated time on study treatment is based on continued clinical benefit, i.e., until disease progression or unacceptable toxicity. The target sample size is 932 participants.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Atezolizumab will be administered intravenously at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. Participants will receive atezolizumab as long as they continue to experience clinical benefit in the opinion of the investigator until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator.
atezolizumab (mpdl3280a) [tecentriq], an engineered anti-pdl1 antibody Tecentriq
Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.
(Active Comparator)
Participants randomized to the chemotherapy arm will receive vinflunine, paclitaxel, or docetaxel per the investigator's choice. Vinflunine 320 milligrams per square meter (mg/m^2), paclitaxel 175 mg/m^2, or docetaxel 75 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle until disease progression per standard RECIST v1.1 or unacceptable toxicity.
docetaxel
Docetaxel 75 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle.
paclitaxel
Paclitaxel 175 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle.
vinflunine
Vinflunine 320 mg/m^2 will be administered intravenously on Day 1 of each 21-day cycle.

Primary Outcomes

Measure
Overall Survival
time frame: Between randomization and death due to any cause, up to approximately 25 months after first participant enrolled

Secondary Outcomes

Measure
Percentage of Participants With Objective Response as Determined by the Investigator With Use of Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)
time frame: Up to approximately 25 months after first participant enrolled
Progression-free Survival (PFS) as Determined by the Investigator With Use of RECIST v1.1
time frame: Up to approximately 25 months after first participant enrolled
Duration of Response (DOR) as Determined by the Investigator With Use of RECIST v1.1
time frame: Up to approximately 25 months after first participant enrolled
Percentage of Participants With Adverse Events (AEs)
time frame: Up to approximately 25 months after first participant enrolled
Percentage of Participants With Anti-therapeutic Antibodies (ATA) to Atezolizumab
time frame: Predose (0 hours) on Day 1 of Cycles 1, 2, 3, 4 and every 8 cycles thereafter; at treatment discontinuation (up to 25 months); at 120 days after last dose of atezolizumab (up to 25 months; each cycle is 21 days)
Maximum Observed Serum Atezolizumab Concentration (Cmax)
time frame: Predose (0 hours) on Day 1 of Cycles 1, 2, 3, 4, every 8 cycles thereafter; 30 minutes postdose on Day 1 of Cycle 1; at treatment discontinuation (up to 25 months); at 120 days after last dose of atezolizumab (up to 25 months; each cycle is 21 days)
Minimum Observed Serum Atezolizumab Concentration (Cmin)
time frame: Predose (0 hours) on Day 1 of Cycles 1, 2, 3, 4 and every 8 cycles thereafter; at treatment discontinuation (up to 25 months); at 120 days after last dose of atezolizumab (up to 25 months; each cycle is 21 days)
European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score
time frame: Cycle 1 Day 1 (prior to any health care interaction), on Day 1 of each subsequent cycle, and at 30 days after the last treatment dose (Up to approximately 25 months; each cycle is 21 days)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically or cytologically documented locally advanced or metastatic UBC (including renal pelvis, ureters, urinary bladder, and urethra) - Representative tumor specimens as specified by the protocol - Disease progression during or following treatment with at least one platinum-containing regimen for inoperable, locally advanced or metastatic UBC or disease recurrence - 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 - For female participants of childbearing potential and male participants with partners of childbearing potential, agreement (by participant and/or partner) to use highly effective form(s) of contraception as defined by the protocol and to continue its use 90 days after the last dose of atezolizumab 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 - Malignancies other than UBC within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome, or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer - Pregnant and lactating women - Significant cardiovascular disease - Severe infections within 4 weeks prior to randomization - Major surgical procedure other than for diagnosis within 4 weeks prior to randomization - 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 formulation - History of autoimmune disease - Prior allogeneic stem cell or solid organ transplant - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan - Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or hepatitis C or tuberculosis - Administration of a live, attenuated vaccine within 4 weeks prior to randomization - Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1) or anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibodies

Additional Information

Official title A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer After Failure With Platinum-Containing Chemotherapy
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.