Overview

This trial is active, not recruiting.

Condition renal cell carcinoma
Treatments atezolizumab, bevacizumab, sunitinib
Phase phase 2
Targets PD-1, VEGF, PDGF, FLT-3, KIT
Sponsor Hoffmann-La Roche
Start date January 2014
End date August 2019
Trial size 305 participants
Trial identifier NCT01984242, 2013-003167-58, WO29074

Summary

This multicenter, randomized, open-label study will evaluate the efficacy, safety and tolerability of atezolizumab as monotherapy or in combination with bevacizumab versus sunitinib in participants with histologically confirmed, previously untreated locally advanced or metastatic renal cell carcinoma who have not received prior systemic therapy either in the adjuvant or metastatic setting.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Primary purpose treatment
Masking no masking
Arm
(Experimental)
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
atezolizumab Tecentriq, MPDL3280A, RO5541267
1200 mg IV q3w
bevacizumab Avastin
15 mg/kg IV q3w
(Experimental)
Atezolizumab 1200 mg IV infusions q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants may crossover to receive atezolizumab + bevacizumab combination until disease progression, unacceptable toxicity, withdrawal from study, or study completion or termination.
atezolizumab Tecentriq, MPDL3280A, RO5541267
1200 mg IV q3w
(Active Comparator)
Sunitinib 50 mg orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants (except EU participants) may crossover to receive atezolizumab + bevacizumab combination until disease progression, unacceptable toxicity, withdrawal from study, or study completion or termination.
sunitinib Sutent
50 mg orally once daily for 4 weeks, followed by 2 weeks of rest

Primary Outcomes

Measure
Progression-Free Survival per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1) via Central Independent Review Committee (IRC) Assessment in Intent-to-Treat (ITT) Population
time frame: From randomization until disease progression or death from any cause (up to approximately 2.5 years)
Progression-Free Survival per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1) via Central IRC Assessment in Participants who Have Detectable PD-L1 Expression
time frame: From randomization until disease progression or death from any cause (up to approximately 2.5 years)

Secondary Outcomes

Measure
Progression-Free Survival per RECIST v.1.1 in Participants who Have Tumors With Higher Than Median Expression of an Immune Gene Signature
time frame: From randomization until disease progression or death from any cause (up to approximately 2.5 years)
Progression-Free Survival per RECIST v.1.1 in Participants who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature
time frame: From randomization until disease progression or death from any cause (up to approximately 2.5 years)
Progression-Free Survival Using Investigator Assessment
time frame: From randomization until disease progression or death from any cause (up to approximately 2.5 years)
Percentage of Participants With Overall Response (Complete + Partial Response [CR+PR]) per RECIST v1.1 Using Investigator Assessment
time frame: From randomization until disease progression or death from any cause (up to approximately 2.5 years)
Percentage of Participants With Overall Response (CR+PR) per RECIST v1.1 via an Independent Central Radiologic Review
time frame: From randomization until disease progression or death from any cause (up to approximately 2.5 years)
Percentage of Participants With Overall Response per Modified RECIST Using Investigator Assessment
time frame: From randomization until disease progression or death from any cause (up to approximately 2.5 years)
Progression-Free Survival per Modified RECIST Using Investigator Assessment
time frame: From randomization until disease progression or death from any cause (up to approximately 2.5 years)
Duration of Response per RECIST v1.1 Criteria
time frame: From randomization until disease progression or death from any cause (up to approximately 2.5 years)
Duration of Response per Modified RECIST Criteria
time frame: From randomization until disease progression or death from any cause (up to approximately 2.5 years)
Overall Survival
time frame: From randomization up to death or study completion (Up to approximately 2.5 years)
Percentage of Crossover Treatment Phase Participants With a Best Overall Response of CR or PR
time frame: From Day 1 of crossover Cycle 1 (cycle length=6 weeks) until disease progression or death from any cause (up to approximately 1.5 years)
Duration of Response in Crossover Treatment Phase Participants
time frame: From Day 1 of crossover Cycle 1 (cycle length=6 weeks) until disease progression or death from any cause (up to approximately 1.5 years)
Progression-Free Survival in Crossover Treatment Phase Participants
time frame: From Day 1 of crossover Cycle 1 (cycle length=6 weeks) until disease progression or death from any cause (up to approximately 1.5 years)
Percentage of Participants With Adverse Events
time frame: From randomization until 30 days after last dose of study treatment (up to approximately 5 years)
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Atezolizumab
time frame: Pre-infusion (0 hour) (infusion duration = 60 minutes) on Day 1 of Cycles 1, 2, 4 and 8, thereafter every 8 cycles (each cycle = 6 weeks) until end of treatment visit (up to approximately 2.5 years)
Maximum Serum Concentration (Cmax) of Atezolizumab
time frame: 30 min post-infusion (infusion duration = 60 minutes) on Cycle 1 (cycle length = 6 weeks), Day 1
Minimum Serum Concentration (Cmin) of Atezolizumab
time frame: Pre-infusion (0 hour) on Day 1 of Cycles 1, 2, and 4; Day 22 of Cycles 1, 2, and 4 (each cycle = 6 weeks); and at study termination (up to approximately 2.5 years)
Cmax of Bevacizumab
time frame: 30 min post-infusion (infusion duration = 90 minutes) on Day 1 of Cycles 1 and 2 (each cycle = 6 weeks)
Cmin of Bevacizumab
time frame: Pre-infusion (0 hour) (infusion duration = 60 minutes) on Day 1 of Cycles 1 and 2 (each cycle = 6 weeks), and at study termination (up to approximately 2.5 years)
M.D. Anderson Symptom Inventory (MDASI) Score
time frame: From randomization up to end of treatment (up to approximately 2.5 years)
Brief Fatigue Inventory (BFI) Score
time frame: From randomization up to end of treatment (up to approximately 2.5 years)
Euro Quality of Life 5 Dimension Questionnaire (EQ-5D) Score
time frame: From randomization up to end of treatment (up to approximately 2.5 years)

Eligibility Criteria

All participants at least 18 years old.

Inclusion Criteria: - Unresectable advanced or metastatic renal cell carcinoma with component of clear cell histology and/or component of sarcomatoid histology that has not been previously treated with any systemic agents, including treatment in the adjuvant setting - Measurable disease, as defined by RECIST v1.1 - Karnofsky performance score greater than or equal to (>/=) 70 - Adequate hematologic and end-organ function as defined by protocol - Women of childbearing potential and male participants with partners of childbearing potential must agree to use highly effective methods of contraception as defined by protocol Exclusion Criteria: Disease-Specific Exclusions: - Radiotherapy for renal cell carcinoma within 14 days prior to Cycle 1, Day 1 with the exception of: Single-fraction radiotherapy given for the indication of pain control - Known active malignancies or metastasis of the brain or spinal cord or leptomeningeal disease, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) - Uncontrolled hypercalcemia or symptomatic hypercalcemia - Malignancies other than renal cell carcinoma within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death, treated with expected curative outcome General Medical Exclusions: - Life expectancy of less than (<) 12 weeks - Pregnant and lactating women - History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins - History of autoimmune disease - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan - Participants with active or chronic hepatitis B, active hepatitis C, Human Immunodeficiency Virus (HIV) positive test, significant cardiovascular disease - Prior allogeneic stem cell or solid organ transplant Exclusion Criteria Related to Medications: - Prior treatment with Cluster of Differentiation 137 (CD137) agonists, anti-Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4), anti-PD-1, or anti PD-L1 therapeutic antibody or pathway-targeting agents - Treatment with systemic immunostimulatory agents for any reason within 6 weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1 - Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1 Bevacizumab- and Sunitinib-Specific Exclusions: - Inadequately controlled hypertension - Prior history of hypertensive crisis or hypertensive encephalopathy - New York Heart Association Class II or greater congestive heart failure - History of myocardial infarction or unstable angina, stroke or transient ischemic attack within 3 months prior to Cycle 1, Day 1

Additional Information

Official title A Phase II, Randomized Study of Atezolizumab (Anti PD-L1 Antibody) Administered as Monotherapy or in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma
Trial information was received from ClinicalTrials.gov and was last updated in March 2017.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.