A Study of Atezolizumab Versus Placebo as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Bladder Cancer Who Are ctDNA Positive Following Cystectomy

Phase 3

Active, not recruiting

• Conditions: Muscle-invasive Bladder Cancer
• Interventions: Drug: Atezolizumab; Other: Placebo; Device: Signatera

• Registration Number: NCT04660344
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This is a global Phase III, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of adjuvant treatment with atezolizumab compared with placebo in participants with MIBC who are ctDNA positive and are at high risk for recurrence following cystectomy.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-12-01
• Study First Submitted QC: 2020-12-07
• Study First Posted: 2020-12-09
• Study Start: 2021-05-03
• Status Verified: 2025-06
• Primary Completion: 2025-06-15
• Last Update Submitted: 2025-06-19
• Last Update Posted: 2025-06-22
• Study Completion: 2026-09-13

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 761

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: Atezolizumab	Atezolizumab	Atezolizumab will be administered intravenously at a dose of 1680 milligrams (mg) on Day 1 of each 28-day cycle for 12 cycles or up to 1 year (whichever occurs first). Atezolizumab will be discontinued in the event of disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination by the Sponsor.
Arm A: Atezolizumab	Signatera	Atezolizumab will be administered intravenously at a dose of 1680 milligrams (mg) on Day 1 of each 28-day cycle for 12 cycles or up to 1 year (whichever occurs first). Atezolizumab will be discontinued in the event of disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination by the Sponsor.
Arm B: Placebo	Placebo	Placebo will be administered intravenously on Day 1 of each 28-day cycle. Placebo will be discontinued in the event of disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination by the Sponsor.
Arm B: Placebo	Signatera	Placebo will be administered intravenously on Day 1 of each 28-day cycle. Placebo will be discontinued in the event of disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination by the Sponsor.
Arm C: Surveillance Follow-Up	Signatera	Participants who remain ctDNA negative at 12 months from the date of cystectomy will not be randomized to treatment and will enter follow-up.

Primary Outcome Measures

Name	Time	Method
Investigator-assessed DFS	Randomization up to first occurrence of DFS event (up to approximately 40 months)	Investigator-assessed disease-free survival (DFS), defined as the time from randomization to the first occurrence of a DFS event, defined as any of the following: * Local (pelvic) recurrence of urothelial carcinoma (UC) (including soft tissue and regional lymph nodes); * Urinary tract recurrence of UC (including all pathological stages and grades); * Distant metastasis of UC; * Death from any cause

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	Randomization up to death from any cause (up to approximately 10 years)	Overall survival (OS), defined as the time from randomization to death from any cause.
Independent Review Facility (IRF)-Assessed DFS	Randomization up to first occurrence of DFS event (up to approximately 40 months)
Investigator-Assessed Disease-Specific Survival	Randomization to death from UC (up to approximately 10 years)	Investigator-assessed disease-specific survival, defined as the time from randomization to death from UC per investigator assessment of cause of death.
Investigator-Assessed Distant Metastasis-Free Survival	Randomization to diagnosis of distant metastases or death from any cause (up to approximately 10 years)	Investigator-assessed distant metastasis-free survival, defined as the time from randomization to the diagnosis of distant (i.e., non-locoregional) metastases or death from any cause.
Time to Confirmed Deterioration of Function and Health Related Quality of Life (HRQoL)	Randomization to participant's first score decrease of >=10 points from Baseline on EORTC QLQ-C30 physical function scale, role function scale, and the GHS/QoL Scale (up to approximately 10 years)	Time to confirmed deterioration of function and health-related quality of life (HRQoL), defined as the time from randomization to the date of a participant's first score decrease of \>= 10 points from baseline on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) physical function scale, role function scale, and the global health status (GHS)/QoL scale (separately), held for at least two consecutive time points or followed by death.
ctDNA Clearance	Baseline, Cycle 3 Day 1 or Cycle 5 Day 1 (each cycle is 28 days)	ctDNA clearance, defined as the proportion of patients who are ctDNA positive at baseline and ctDNA negative at Cycle 3, Day 1 or Cycle 5, Day 1.
Percentage of Participants With Adverse Events	Baseline up to approximately 10 years
Serum Concentration of Atezolizumab	At pre-defined intervals from first administration of study drug up to approximately 10 years
Incidence of Anti-Drug Antibodies (ADAs) to Atezolizumab	Baseline up to approximately 10 years	Incidence of anti-drug antibodies (ADAs) to atezolizumab after initiation of study treatment (postbaseline incidence).
Prevalence of ADAs to Atezolizumab	Baseline	Prevalence of ADAs to atezolizumab at baseline.

Trial Locations

Locations (167)

UCLA Department of Medicine; 🇺🇸 Santa Monica, California, United States

Rocky Mountain Cancer Center - Denver; 🇺🇸 Littleton, Colorado, United States

Cancer Care Centers of Brevard; 🇺🇸 Rockledge, Florida, United States

Optum Health Care; 🇺🇸 Las Vegas, Nevada, United States

Wake Forest Baptist Medical Center; 🇺🇸 Winston-Salem, North Carolina, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

AHN Cancer Institute ? Allegheny General Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

Centro Medico Austral; 🇦🇷 Buenos Aires, Argentina

Instituto Alexander Fleming; 🇦🇷 Buenos Aires, Argentina

AZ KLINA; 🇧🇪 Brasschaat, Belgium

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