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A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma [IMmotion151]

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ClinicalTrials.gov Identifier: NCT02420821
Recruitment Status : Active, not recruiting
First Posted : April 20, 2015
Last Update Posted : January 19, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This multi-center, randomized, open-label study will evaluate the efficacy and safety of atezolizumab (MPDL3280A) plus bevacizumab versus sunitinib in participants with inoperable, locally advanced, or metastatic renal cell carcinoma (RCC) who have not received prior systemic active or experimental therapy, either in the adjuvant or metastatic setting.

Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma Drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody Drug: Bevacizumab Drug: Sunitinib Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 915 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Open-Label, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Bevacizumab Versus Sunitinib in Patients With Untreated Advanced Renal Cell Carcinoma
Actual Study Start Date : May 31, 2015
Estimated Primary Completion Date : July 31, 2020
Estimated Study Completion Date : July 31, 2020


Arm Intervention/treatment
Experimental: Atezolizumab + Bevacizumab
Participants assigned to a dual regimen of atezolizumab plus bevacizumab will receive both agents until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody
Atezolizumab at a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on Days 1 and 22 of each 42-day cycle until loss of clinical benefit, unacceptable toxicity, symptomatic deterioration attributed to disease progression, or death.
Other Name: Tecentriq, MPDL3280A
Drug: Bevacizumab
Bevacizumab as 15 milligrams per kilogram (mg/kg) via IV infusion on Days 1 and 22 of each 42-day cycle until loss of clinical benefit, unacceptable toxicity, symptomatic deterioration attributed to disease progression, or death.
Other Name: Avastin
Active Comparator: Sunitinib
Participants assigned to receive sunitinib single-agent chemotherapy will receive treatment until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Drug: Sunitinib
Sunitinib as 50 mg orally, once daily on Days 1 through 28 of each 42-day cycle until loss of clinical benefit, unacceptable toxicity, symptomatic deterioration attributed to disease progression, or death.
Other Name: Sutent



Primary Outcome Measures :
  1. Progression-Free Survival (PFS) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) in Participants with Detectable Programmed Death-Ligand 1 (PD-L1) [ Time Frame: Baseline until confirmed disease progression or death, whichever occurs first (assessed at baseline, Week 12, then every 6 weeks through Week 78 and then every 12 weeks thereafter until disease progression [up to 63 months]) ]
  2. Overall Survival (OS) in all Randomized Participants [ Time Frame: Baseline until death due to any cause (up to 63 months) ]

Secondary Outcome Measures :
  1. OS in Participants with Detectable PD-L1 [ Time Frame: Baseline until death due to any cause (up to 63 months) ]
  2. PFS as Determined by an Independent Review Committee (IRC) According to RECIST v1.1 [ Time Frame: Baseline until confirmed disease progression or death, whichever occurs first (assessed at baseline, Week 12, then every 6 weeks through Week 78 and then every 12 weeks thereafter until disease progression [up to 63 months]) ]
  3. Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by the Investigator According to RECIST v1.1 [ Time Frame: Baseline until confirmed disease progression or death, whichever occurs first (assessed at baseline, Week 12, then every 6 weeks through Week 78 and then every 12 weeks thereafter until disease progression [up to 63 months]) ]
  4. Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 [ Time Frame: Baseline until confirmed disease progression or death, whichever occurs first (assessed at baseline, Week 12, then every 6 weeks through Week 78 and then every 12 weeks thereafter until disease progression [up to 63 months]) ]
  5. Percentage of Participants With an Objective Response of CR or PR as Determined by an IRC According to RECIST v1.1 [ Time Frame: Baseline until confirmed disease progression or death, whichever occurs first (assessed at baseline, Week 12, then every 6 weeks through Week 78 and then every 12 weeks thereafter until disease progression [up to 63 months]) ]
  6. DOR as Determined by an IRC According to RECIST v1.1 [ Time Frame: Baseline until confirmed disease progression or death, whichever occurs first (assessed at baseline, Week 12, then every 6 weeks through Week 78 and then every 12 weeks thereafter until disease progression [up to 63 months]) ]
  7. PFS as Determined by the Investigator According to Modified RECIST [ Time Frame: Baseline until confirmed disease progression or death, whichever occurs first (assessed at baseline, Week 12, then every 6 weeks through Week 78 and then every 12 weeks thereafter until disease progression [up to 63 months]) ]
  8. Percentage of Participants With an Objective Response of CR or PR as Determined by the Investigator According to Modified RECIST [ Time Frame: Baseline until confirmed disease progression or death, whichever occurs first (assessed at baseline, Week 12, then every 6 weeks through Week 78 and then every 12 weeks thereafter until disease progression [up to 63 months]) ]
  9. DOR as Determined by the Investigator According to Modified RECIST [ Time Frame: Baseline until confirmed disease progression or death, whichever occurs first (assessed at baseline, Week 12, then every 6 weeks through Week 78 and then every 12 weeks thereafter until disease progression [up to 63 months]) ]
  10. PFS in All Randomized Participants as Determined by the Investigator According to RECIST v1.1 [ Time Frame: Baseline until confirmed disease progression or death, whichever occurs first (assessed at baseline, Week 12, then every 6 weeks through Week 78 and then every 12 weeks thereafter until disease progression [up to 63 months]) ]
  11. PFS in Participants With Sarcomatoid Histology as Determined by the Investigator According to RECIST v1.1 [ Time Frame: Baseline until confirmed disease progression or death, whichever occurs first (assessed at baseline, Week 12, then every 6 weeks through Week 78 and then every 12 weeks thereafter until disease progression [up to 63 months]) ]
  12. OS in Participants With Sarcomatoid Histology [ Time Frame: Baseline until death due to any cause (up to 63 months) ]
  13. Change From Baseline in Symptom Interference as Determined by M.D. Anderson Symptom Inventory (MDASI) Part II [ Time Frame: Baseline up to 63 months (assessed on Day 1 and Day 22 of each cycle up to treatment discontinuation [up to 63 months], at 6, 12, 24, and 36 weeks after treatment discontinuation [up to 63 months]) (Cycle = 42 days) ]
  14. Change From Baseline in Symptom Severity as Determined by MDASI [ Time Frame: Baseline up to 63 months (assessed on Day 1 and Day 22 of each cycle up to treatment discontinuation [up to 63 months], at 6, 12, 24, and 36 weeks after treatment discontinuation [up to 63 months]) (Cycle = 42 days) ]
  15. Change From Baseline in Symptom Severity as Determined by Brief Fatigue Inventory (BFI) [ Time Frame: Baseline up to 63 months (assessed on Day 1 and Day 22 of each cycle and weekly during the first 12 weeks, up to treatment discontinuation [up to 63 months], at 6, 12, 24, and 36 weeks after treatment discontinuation [up to 63 months]) (Cycle = 42 days) ]
  16. Change From Baseline in Treatment Side Effects Subscale From Functional Assessment of Cancer Therapy Kidney Symptom Index (FKSI-19) [ Time Frame: Baseline up to 63 months (assessed on Day 1 and Day 22 of each cycle up to treatment discontinuation [up to 63 months], at 6, 12, 24, and 36 weeks after treatment discontinuation [up to 63 months]) (Cycle = 42 days) ]
  17. Change From Baseline in Health-Related Quality of Life as Determined by European Quality of Life 5-Dimension (EQ-5D) Scores [ Time Frame: Baseline up to 63 months (assessed on Day 1 and Day 22 of each cycle up to treatment discontinuation [up to 63 months], at 6, 12, 24, and 36 weeks after treatment discontinuation [up to 63 months]) (Cycle = 42 days) ]
  18. Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs) [ Time Frame: Baseline up to 63 months ]
  19. Percentage of Participants With Anti--Therapeutic Antibodies (ATAs) Against Atezolizumab [ Time Frame: Baseline up to 63 months (assessed at pre-dose [Hour 0] on Day 1 of Cycles 1, 2, 4, 8, and every 8 cycles thereafter up to treatment discontinuation [up to 63 months] , and 120 days after last dose [up to 63 months]) (Cycle = 42 days) ]
  20. Maximum Serum Concentration (Cmax) for Atezolizumab [ Time Frame: 30 minutes after the end of atezolizumab infusion (infusion duration: 30-60 minutes) on Cycle 1, Day 1 (Cycle = 42 days) ]
  21. Minimum Serum Concentration (Cmin) for Atezolizumab [ Time Frame: Pre-dose (Hour 0) on Days 1 and 22 of Cycles 1, 2, and 4; pre-dose (Hour 0) on Day 1 of Cycle 8 and every 8 cycles thereafter up to treatment discontinuation (up to 63 months), and 120 days after last dose (up to 63 months) (Cycle = 42 days) ]
  22. Cmax for Bevacizumab [ Time Frame: 30 minutes after the end of atezolizumab infusion (infusion duration: 30-90 minutes) on Cycle 1, Day 1 and Cycle 3, Day 1 (Cycle = 42 days) ]
  23. Cmin for Bevacizumab [ Time Frame: Pre-dose (Hour 0) on Cycle 1, Day 1 and Cycle 3, Day 1, at the treatment discontinuation (up to 63 months), and 120 days after last dose (up to 63 months) (Cycle = 42 days) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Definitive diagnosis of unresectable locally advanced or metastatic RCC with clear-cell histology and/or a component of sarcomatoid carcinoma, with no prior treatment in the metastatic setting
  • Evaluable Memorial Sloan Kettering Cancer Center risk score
  • Measurable disease, as defined by RECIST v1.1
  • Karnofsky performance status greater than or equal to 70%
  • Adequate hematologic and end-organ function prior to randomization

Exclusion Criteria:

Disease-Specific Exclusions:

  • Radiotherapy for RCC within 14 days prior to treatment
  • Active central nervous system disease
  • Uncontrolled pleural effusion, pericardial effusion, or ascites
  • Uncontrolled hypercalcemia
  • Any other malignancies within 5 years except for low-risk prostate cancer or those with negligible risk of metastasis or death

General Medical Exclusions:

  • Life expectancy less than 12 weeks
  • Participation in another experimental drug study within 4 weeks prior to treatment
  • Pregnant or lactating women
  • Known hypersensitivity to any component of atezolizumab or other study medication
  • History of autoimmune disease except controlled, treated hypothyroidism or type I diabetes mellitus
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis
  • Positive human immunodeficiency virus test
  • Active or chronic hepatitis B or C
  • Severe infections within 4 weeks prior to treatment
  • Exposure to oral or IV antibiotics within 2 weeks prior to treatment
  • Live attenuated vaccines within 4 weeks prior to treatment, 28 days prior to randomization, during treatment, or within 5 months following last dose of atezolizumab
  • Significant cardiovascular disease
  • Prior allogeneic stem cell or solid organ transplantation

Exclusion Criteria Related to Medications:

  • Prior treatment with cluster of differentiation 137 agonists, anti-cytotoxic T-lymphocyte associated protein-4, anti-programmed death (PD)-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
  • Treatment with immunostimulatory agents for non-malignant conditions within 6 weeks or immunosuppressive agents within 2 weeks prior to treatment

Bevacizumab- and Sunitinib-Specific Exclusions:

  • History of hypertensive crisis or hypertensive encephalopathy
  • Baseline electrocardiogram showing corrected QT interval greater than 460 milliseconds

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02420821


  Show 165 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02420821     History of Changes
Other Study ID Numbers: WO29637
2014-004684-20 ( EudraCT Number )
First Posted: April 20, 2015    Key Record Dates
Last Update Posted: January 19, 2018
Last Verified: January 2018

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Bevacizumab
Sunitinib
Atezolizumab
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Immunologic Factors