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 circulating tumour deoxyribonucleic acid (ctDNA) positive and are at high risk for recurrence following cystectomy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
761
ctDNA positive participants will receive 1680 mg IV, every 4 weeks (Q4W) on Day 1 of each 28-day cycle.
ctDNA positive participants will receive placebo IV, Q4W on Day 1 of each 28-day cycle
Signatera will be used to evaluate whether ctDNA is detected during serial monitoring of peripheral blood samples for participants enrolled in surveillance. Participants with a ctDNA positive result will be screened for inclusion in the treatment phase. Participants who remain ctDNA negative at 12 months from the date of cystectomy will not be randomized to treatment and will enter follow-up.
Investigator-assessed (INV) - Disease-free Survival (DFS)
INV-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.
Time frame: Randomization up to first occurrence of DFS event (up to approximately 40 months)
Overall survival (OS)
OS, defined as the time from randomization to death from any cause.
Time frame: Randomization up to death from any cause (up to approximately 10 years)
Independent Review Facility (IRF)-assessed DFS
Time frame: Randomization up to first occurrence of DFS event (up to approximately 40 months)
INV Disease-specific Survival (DSS)
INV-DSS, defined as the time from randomization to death from UC per investigator assessment of cause of death.
Time frame: Randomization to death from UC (up to approximately 10 years)
INV Distant Metastasis-free Survival (DMFS)
INV-DMFS, defined as the time from randomization to the diagnosis of distant (i.e., non-locoregional) metastases or death from any cause.
Time frame: Randomization to diagnosis of distant metastases or death from any cause (up to approximately 10 years)
Time to Confirmed Deterioration of Function and Health-related Quality of Life (HRQoL)
Time to confirmed deterioration of function and 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.
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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
...and 151 more locations
Time frame: 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)
ctDNA Clearance
ctDNA clearance, defined as the proportion of participants who are ctDNA positive at baseline and ctDNA negative at Cycle 3, Day 1 or Cycle 5, Day 1.
Time frame: Baseline, Cycle 3 Day 1 or Cycle 5 Day 1 (each cycle is 28 days)
Percentage of Participants With Adverse Events (AEs)
Time frame: Baseline up to approximately 10 years
Serum Concentration of Atezolizumab
Time frame: At pre-defined intervals from first administration of study drug (up to approximately 10 years)
Incidence of Anti-Drug Antibodies (ADAs) to Atezolizumab
Incidence of ADAs to atezolizumab after initiation of study treatment (postbaseline incidence).
Time frame: Baseline up to approximately 10 years
Prevalence of ADAs to Atezolizumab
Prevalence of ADAs to atezolizumab at baseline.
Time frame: Baseline