A Phase III, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of Atezolizumab (Anti-PD-L1 Antibody) as Adjuvant Therapy in Patients With Renal Cell Carcinoma at High Risk of Developing Metastasis Following Nephrectomy

Hoffmann-La Roche186 sites in 3 countries778 target enrollmentJanuary 3, 2017

ConditionsRenal Cell Carcinoma

InterventionsAtezolizumab Placebo

DrugsAtezolizumab

Overview

Phase: Phase 3
Intervention: Atezolizumab
Conditions: Renal Cell Carcinoma
Sponsor: Hoffmann-La Roche
Enrollment: 778
Locations: 186
Primary Endpoint: Investigator-assessed Disease-Free Survival (DFS)
Status: Terminated
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase III, multicenter, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of atezolizumab versus placebo in participants with RCC who are at high risk of disease recurrence following nephrectomy.

Registry

clinicaltrials.gov

Start Date

January 3, 2017

End Date

December 8, 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

•ECOG performance status of less than or equal to (\</=) 1
•Pathologically confirmed RCC with a component of either clear cell histology or sarcomatoid histology that has not been previously treated in the adjuvant or neoadjuvant setting and classified as being at high risk of RCC recurrence
•Radical or partial nephrectomy with lymphadenectomy in select participants
•Absence of residual disease and absence of metastasis, as confirmed by a negative baseline computed tomography (CT) of the pelvis, abdomen, and chest no more than 4 weeks prior to randomization. Confirmation of disease-free status will be assessed by an independent central radiologic review of imaging data.
•Absence of brain metastasis, as confirmed by a negative CT with contrast or magnetic resonance imaging (MRI) scan of the brain, no more than 4 weeks prior to randomization. Applicable only to metastasectomy participants
•Full recovery from nephrectomy or metastasectomy within 12 weeks from randomization following surgery

Exclusion Criteria

•Bilateral synchronous tumors with inheritable forms of RCC including von Hippel-Lindau
•Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
•Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days or five half-lives of the investigational agent, whichever is longer, prior to enrollment
•Malignancies other than RCC within 5 years prior to Cycle 1, Day 1
•History of autoimmune disease
•Participants with prior allogeneic stem cell or solid organ transplantation
•History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan
•Positive test for HIV
•Participants with active hepatitis B or hepatitis C
•Active tuberculosis

Arms & Interventions

Atezolizumab

Participants will receive atezolizumab 1200 milligrams (mg) intravenous (IV) infusion every 3 weeks (q3w) for 16 cycles (each cycle=21 days) or 1 year (whichever occurs first).

Intervention: Atezolizumab

Placebo

Participants will receive placebo matching to atezolizumab q3w for 16 cycles (each cycle=21 days) or 1 year (whichever occurs first).

Intervention: Placebo

Outcomes

Primary Outcomes

Investigator-assessed Disease-Free Survival (DFS)

Time Frame: From baseline up to first occurence of event by investigator assessment (up to approximately 64 months)

Investigator-assessed DFS, defined as the time from randomization to death from any cause or the first documented recurrence assessed by investigator, whichever occurred first. Recurrence was defined as any of the following: Local recurrence of renal cell carcinoma (RCC), new primary RCC, or distant metastasis of RCC. Investigator-assessed DFS was analyzed similarly to the analysis of IRF-assessed DFS.

Secondary Outcomes

Independent Review Facility (IRF)-Assessed DFS(From baseline until first documented recurrence event (up to approximately 64 months))
Overall Survival (OS)(From baseline up to death due to any cause (up to approximately 64 months))
Investigator-assessed DFS in Participants With Tumor-Infiltrating Immune Cell (IC) 1/2/3(From baseline until first occurrence of DFS event (up to approximately 64 months))
IRF-assessed Event-free Survival (EFS)(From baseline until first documented recurrence event (up to approximately 64 months))
Disease-Specific Survival(From baseline up to death due to RCC (up to approximately 64 months))
IRF-assessed DFS in Participants With Tumor-Infiltrating IC 1/2/3(From baseline until first occurrence of DFS event (up to approximately 64 months))
Distant Metastasis-Free Survival(From baseline up to date of diagnosis of distant metastases or death due to any cause (up to approximately 64 months))
Percentage of Participants Who Are Alive and Investigator-assessed Recurrence Free at Year 1, 2, and 3(Up to 3 years)
Percentage of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab(Predose (hr 0) on Day 1 of Cycles 1, 2, 3, 4, 8; at treatment discontinuation (up to 1 year); 90-120 days after last dose (last dose = up to 1 year) (Cycle=21 days))
Percentage of Participants Who Are Alive and IRF-assessed Recurrence Free at Year 1, 2, and 3(Up to 3 years)
Maximum Serum Concentration (Cmax) of Atezolizumab(Predose (Hour[hr]0), 0.5 hr after end of infusion (infusion duration=1 hr) on Cycle 1 Day 1; predose (hr 0) on Day 1 of Cycles 2, 3, 4, 8; at treatment discontinuation (up to 1 year); 90-120 days after last dose (last dose = up to 1 year) (Cycle=21 days))
Percentage of Participants With Adverse Events(From baseline up to death due to any cause (up to approximately 71 months))
Minimum Serum Concentration (Cmin) of Atezolizumab(Predose (Hour[hr]0), 0.5 hr after end of infusion (infusion duration=1 hr) on Cycle 1 Day 1; predose (hr 0) on Day 1 of Cycles 2, 3, 4, 8; at treatment discontinuation (up to 1 year); 90-120 days after last dose (last dose = up to 1 year) (Cycle=21 days))