Overview

This trial is active, not recruiting.

Condition renal cell carcinoma
Treatments atezolizumab [tecentriq], bevacizumab [avastin], 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 and safety of atezolizumab as monotherapy or in combination with Avastin (bevacizumab) versus sunitinib in patients with previously untreated locally advanced or metastatic renal cell carcinoma. Patients in Arm A will receive atezolizumab 1200 mg IV every 3 weeks (6-week cycles) plus Avastin 15 mg/kg IV until disease progression. Patients in Arm B will receive atezolizumab alone (until disease progression), and patients in Arm C will receive sunitinib 50 mg orally daily for 4 weeks followed by 2 weeks rest until disease progression. Following disease progression, patients in Arms B and C will be given the option to receive combination treatment with atezolizumab and Avastin.

Patients enrolled into arm B (atezolizumab alone) in Europe (including France, Italy, the United Kingdom, Romania, Spain, Germany, the Czech Republic and Poland) are not eligible to cross over into arm A to receive combination treatment with atezolizumab and bevacizumab following disease progression, per local regulatory requirement.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
atezolizumab [tecentriq]
1200 mg IV q3w dosed in 6-week cycles until disease progression
bevacizumab [avastin]
15 mg/kg IV q3w (dosed in 6-week cycles), until disease progression
(Experimental)
atezolizumab [tecentriq]
1200 mg IV q3w dosed in 6-week cycles until disease progression
atezolizumab [tecentriq]
Following disease progression: 1200 mg IV q3w dosed in 6-week cycles, until disease progression
bevacizumab [avastin]
Following disease progression: 15 mg/kg IV q3w (dosed in 6-week cycles), until disease progression
(Active Comparator)
atezolizumab [tecentriq]
Following disease progression: 1200 mg IV q3w dosed in 6-week cycles, until disease progression
bevacizumab [avastin]
Following disease progression: 15 mg/kg IV q3w (dosed in 6-week cycles), until disease progression
sunitinib
50 mg/day orally for 4 weeks, followed by 2 weeks of rest (dosed on 6-week cycles), until disease progression

Primary Outcomes

Measure
Progression-free survival per RECIST v.1.1 via central IRC assessment
time frame: Up to 2.5 years

Secondary Outcomes

Measure
Progression-free survival using investigator assessment per immune-related criteria
time frame: Up to 2.5 years
Overall response rate (complete + partial response)
time frame: Up to 2.5 years
Duration of response
time frame: approximately 2.5 years
Overall survival
time frame: Up to 2.5 years
Overall response rate in patients progressing on the sunitinib and MPDL alone arms who subsequently cross over to atezolizumab + Avastin treatment
time frame: Up to 1.5 years
Duration of response in patients progressing on the sunitinib and MPDL alone arms who subsequently cross over to atezolizumab + Avastin treatment
time frame: approximately 1.5 years
Progression-free survival in patients progressing on the sunitinib and MPDL alone arms who subsequently cross over to atezolizumab + Avastin treatment
time frame: Up to 1.5 years
Safety: Incidence of adverse events
time frame: approximately 2.5 years
Pharmacokinetics of atezolizumab alone and in combination with bevacizumab: Area under the concentration-time curve
time frame: Cycle 1

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Adult patients >/= 18 years of age - 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 >/= 70 - Adequate hematologic and end-organ function as defined by protocol - Women of childbearing potential and male patients must agree to use adequate methods of contraception as defined by protocol during the treatment period and for at least 6 months after the last dose of atezolizumab or Avastin (bevacizumab) for patients randomized to Arm A, or at least 90 days after the last dose of atezolizumab monotherapy for patients randomized to Arm B, or at least 30 days after the last dose of sunitinib for patients randomized to Arm C. Exclusion Criteria: - Radiotherapy for RCC within 28 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 CT or 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 RCC 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 - Life expectancy of < 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 (Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study) Bevacizumab- and Sunitinib-Specific Exclusions: - Inadequately controlled hypertension - Prior history of hypertensive crisis or hypertensive encephalopathy

Additional Information

Official title A Phase II, Randomized Study of Atezolizumab Administered as Monotherapy or In Combination With Bevacizumab Versus Sunitinib In Patients With Untreated Advanced Renal Cell Carcinoma
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.