A study comparing the treatment benefits of Atezolizumab MPDL32018 used alone and used together with Avastin to Sunitinib. Benefit is being studied in patients who have advanced kidney cancer or kidney cancer which has spread to other parts of the body and has not been treated before.

Phase 1

• Conditions: ADVANCED RENAL CELL CARCINOMA; MedDRA version: 20.1 Level: LLT Classification code 10023400 Term: Kidney cancer System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-003167-58-DE
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-03-13
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 305

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 - Adequate hematologic and end-organ function as defined by protocol
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of atezolizumab and bevacizumab for patients randomized to Arm A or patients treated with this combination in the crossover treatment phase, or 5 months after the last dose of atezolizumab monotherapy for patients randomized to Arm B, or 30 days after the last dose of sunitinib for patients randomized Arm C.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

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 malignancies or metastasis of the brain or spinal cord or leptomeningeal disease
- 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary efficacy objective of the study is to estimate the efficacy of atezolizumab + bevacizumab and atezolizumab monotherapy compared with sunitinib as measured by PFS per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) via an independent central radiologic review in the ITT population and in patients who have detectable levels of PD-L1 expression on tumor-infiltrating immune cells (immunohistochemistry [IHC] IC1/2/3).;Secondary Objective: To evaluate the efficacy of atezolizumab + bevacizumab and atezolizumab monotherapy versus sunitinib as assessed by PFS per RECIST v1.1 in patients who have tumors with higher than the 33rd percentile expression of an immune gene signature, defined as the average expression of CD274, CD8A, GZMB, PDCD1, and IFN-?;Primary end point(s): Progression-free survival per RECIST v.1.1 via central ICR assessment;Timepoint(s) of evaluation of this end point: approximately 2.5 years

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): - Progression-free survival using investigator assessment per immune-related criteria<br> - Overall response rate <br> - Duration of response<br> - Overall survival<br> - Overall response rate in patients progressing on the sunitinib and MPDL alone arms who subsequently cross over to MPDL3280A + Avastin treatment<br> ;Timepoint(s) of evaluation of this end point: approximately 2.5 years