A Phase III, Open-Label, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Versus Observation as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Urothelial Carcinoma After Surgical Resection

Hoffmann-La Roche186 sites in 4 countries809 target enrollmentOctober 5, 2015

ConditionsCarcinoma, Transitional Cell

InterventionsAtezolizumab

Overview

Phase: Phase 3
Intervention: Atezolizumab
Conditions: Carcinoma, Transitional Cell
Sponsor: Hoffmann-La Roche
Enrollment: 809
Locations: 186
Primary Endpoint: Disease-Free Survival (DFS), as Assessed by Investigator
Status: Terminated
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This Phase III, open-label, randomized, multicenter study is to evaluate the efficacy and safety of adjuvant treatment with atezolizumab compared with observation in participants with muscle-invasive UC who are at high risk for recurrence following resection. Eligible participants were randomized by a 1:1 ratio into atezolizumab group or control group.

Registry

clinicaltrials.gov

Start Date

October 5, 2015

End Date

June 14, 2022

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically confirmed muscle-invasive UC (also termed transitional cell carcinoma) of the bladder or upper urinary tract (i.e., renal pelvis or ureters)
•For participants treated with prior neoadjuvant chemotherapy: tumor stage of ypT2-4a or ypN+ (ypT2-4 or ypN+ for participants with upper urinary tract UC) and M0
•For participants who have not received prior neoadjuvant chemotherapy: tumor stage of pT3-4a or pN+ (pT3-4 or pN+ for participants with upper urinary tract UC) and M0
•Representative formalin-fixed paraffin-embedded tumor specimens from surgical resection (i.e., radical cystectomy, nephroureterectomy, or lymph node dissection) in paraffin blocks (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for central testing and determined to be evaluable for tumor programmed death-ligand 1 (PD-L1) expression prior to study enrollment
•Absence of residual disease and absence of metastasis, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging scan of the pelvis, abdomen, and chest no more than 4 weeks prior to randomization
•Full recovery from cystectomy or nephroureterectomy within 14 weeks following surgery
•Eastern Cooperative Oncology Group performance status of less than or equal to (\</=) 2
•Life expectancy greater than or equal to (\>/=) 12 weeks
•Adequate hematologic and end-organ function
•For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use contraceptive methods that result in a failure rate of less than (\<) 1 percent (%) per year during the treatment period and for at least 5 months after the last dose of atezolizumab

Exclusion Criteria

•Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment
•Adjuvant chemotherapy or radiation therapy for UC following surgical resection
•Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug prior to enrollment
•Malignancies other than UC within 5 years prior to Cycle 1, Day 1
•Pregnancy or breastfeeding
•Significant cardiovascular disease
•Severe infections within 4 weeks prior to Cycle 1, Day 1
•Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1
•History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
•Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation

Arms & Interventions

Atezolizumab

Participants will receive intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).

Intervention: Atezolizumab

Outcomes

Primary Outcomes

Disease-Free Survival (DFS), as Assessed by Investigator

Time Frame: Randomization up to first occurrence of DFS event (up to approximately 50 months)

DFS is defined as the time from randomization to the time of first occurrence of a DFS event. DFS events include: local (pelvic) recurrence of UC (including soft tissue and regional lymph nodes); urinary tract recurrence of UC (including all pathological stages and grades); distant metastasis of UC; or death from any cause. Tumor assessment will be performed using radiographic evaluations.

Secondary Outcomes

Overall Survival (OS)(Randomization until death due to any cause (up to approximately 80 months))
Disease-Specific Survival (DSS), as Assessed by Investigator(Randomization until death due to UC (up to approximately 50 months))
Distant Metastasis-Free Survival (DMFS)(Randomization up to diagnosis of distant metastases or death from any cause (up to approximately 50 months))
Non-Urinary Tract Recurrence-Free Survival (NURFS)(Randomization up to time of first occurrence of a NURFS event (up to approximately 50 months))
Percentage of Participants With Adverse Events (AEs)(Screening up to approximately 80 months)
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab(Baseline up to approximately 50 months)
EuroQol 5-Dimension 5-Level (EQ-5D-5L) Visual Analogue Scale Score(Day 1 of Cycle 1 up to approximately 50 months (Cycle length = 21 days))
Minimum Observed Serum Atezolizumab Concentration (Cmin)(Pre-dose (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, every 8 cycles from Cycle 8, at treatment discontinuation, 120 days after treatment discontinuation (up to approximately 50 months))(Cycle length = 21 days))
Maximum Observed Serum Atezolizumab Concentration (Cmax)(Day 1 of Cycle 1 (Cycle length = 21 days))