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A Study of Atezolizumab (an Engineered Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) as Monotherapy or in Combination With Bevacizumab (Avastin®) Compared to Sunitinib (Sutent®) in Participants With Untreated Advanced Renal Cell Carcinoma (IMmotion150)

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ClinicalTrials.gov Identifier: NCT01984242
Recruitment Status : Active, not recruiting
First Posted : November 14, 2013
Results First Posted : December 21, 2017
Last Update Posted : May 31, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief 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, inoperable, locally advanced or metastatic renal cell carcinoma who have not received prior systemic therapy either in the adjuvant or metastatic setting.

Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody Drug: Bevacizumab Drug: Sunitinib Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 305 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Administered as Monotherapy or in Combination With Bevacizumab Versus Sunitinib in Patients With Untreated Advanced Renal Cell Carcinoma
Actual Study Start Date : January 31, 2014
Actual Primary Completion Date : October 17, 2016
Estimated Study Completion Date : August 31, 2019


Arm Intervention/treatment
Experimental: Atezolizumab and Bevacizumab
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) will be administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody
Atezolizumab will be administered according to the dosage schedule mentioned in the arm description.
Other Names:
  • Tecentriq
  • MPDL3280A
  • RO5541267

Drug: Bevacizumab
Bevacizumab will be administered according to the dosage schedule mentioned in the arm description.
Other Name: Avastin

Experimental: Atezolizumab
Atezolizumab 1200 mg will be administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except European Union [EU] participants) can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody
Atezolizumab will be administered according to the dosage schedule mentioned in the arm description.
Other Names:
  • Tecentriq
  • MPDL3280A
  • RO5541267

Drug: Bevacizumab
Bevacizumab will be administered according to the dosage schedule mentioned in the arm description.
Other Name: Avastin

Active Comparator: Sunitinib
Sunitinib 50 mg will be administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody
Atezolizumab will be administered according to the dosage schedule mentioned in the arm description.
Other Names:
  • Tecentriq
  • MPDL3280A
  • RO5541267

Drug: Bevacizumab
Bevacizumab will be administered according to the dosage schedule mentioned in the arm description.
Other Name: Avastin

Drug: Sunitinib
Sunitinib will be administered according to the dosage schedule mentioned in the arm description.
Other Name: Sutent




Primary Outcome Measures :
  1. Percentage of Participants With Disease Progression Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Via Independent Review Committee (IRC) Assessment or Death in Intent-to-Treat (ITT) Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    Progressive Disease (PD): at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 millimeters (mm); appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

  2. Progression-Free Survival (PFS) Per RECIST v1.1 Via IRC Assessment in ITT Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

  3. Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Immune Cell 1/2/3 (IC1/2/3) Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

  4. PFS Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.


Secondary Outcome Measures :
  1. Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

  2. PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

  3. Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

  4. PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

  5. Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death 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 due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

  6. PFS Per RECIST v1.1 Via IRC Assessment 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 due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

  7. Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death 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 due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

  8. PFS Per RECIST v1.1 Via Investigator Assessment 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 due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

  9. Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in ITT Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

  10. PFS Per RECIST v1.1 Via Investigator Assessment in ITT Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

  11. Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in IC1/2/3 Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

  12. PFS Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

  13. Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) Per RECIST v1.1 Via IRC Assessment in ITT Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to less than (<) 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.

  14. Percentage of Participants With Objective Response Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.

  15. Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in ITT Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.

  16. Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.

  17. Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in ITT Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR.

  18. Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR.

  19. Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in ITT Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm.

  20. PFS Per Modified RECIST Via Investigator Assessment in ITT Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate PFS.

  21. Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in IC1/2/3 Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm.

  22. PFS Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population [ Time Frame: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate PFS.

  23. Duration of Response (DOR) Per RECIST v1.1 Via IRC Assessment in ITT Population [ Time Frame: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.

  24. DOR Per RECIST v1.1 Via Investigator Assessment in ITT Population [ Time Frame: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.

  25. DOR Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population [ Time Frame: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.

  26. DOR Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population [ Time Frame: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.

  27. DOR Per Modified RECIST Via Investigator Assessment in ITT Population [ Time Frame: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate DOR.

  28. DOR Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population [ Time Frame: From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target and all new measurable lesions, taking as reference the baseline sum of diameters, in absence of CR. PD: at least a 20% increase in the sum of diameters of all target and new measurable lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm. Kaplan-Meier methodology was used to estimate DOR.

  29. Percentage of Participants Who Died in ITT Population [ Time Frame: Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
  30. Overall Survival (OS) in ITT Population [ Time Frame: Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier methodology was used to estimate OS.

  31. Percentage of Participants Who Died in IC1/2/3 Population [ Time Frame: Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
  32. OS in IC1/2/3 Population [ Time Frame: Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier methodology was used to estimate OS.

  33. Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in Crossover Population [ Time Frame: From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    Objective Response was defined as CR or PR. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.

  34. DOR Per RECIST v1.1 Via Investigator Assessment in Crossover Population [ Time Frame: From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    DOR was defined as the time from first observation of an objective response (CR or PR) until first observation of PD. CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate DOR.

  35. Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Crossover Population [ Time Frame: From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.

  36. PFS Per RECIST v.1.1 Via Investigator Assessment in Crossover Population [ Time Frame: From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years) ]
    PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.

  37. Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Atezolizumab [ Time Frame: Cycle 1 Day 1 until treatment discontinuation (until data cut-off date 17 October 2016, up to approximately 2.75 years) (1 cycle=6 weeks) ]
    This outcome measure was planned to be analyzed in 'Atezolizumab' and 'Atezolizumab and Bevacizumab' arms only.

  38. Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: 30 minutes after end of infusion on Cycle 1 Day 1 (1 cycle=6 weeks) (infusion length for first dose=60 minutes) ]
  39. Minimum Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Pre-infusion (0 hour) on Day 1 of Cycles 2 and 4; Day 22 of Cycles 1, 2, and 4 (1 cycle=6 weeks) (infusion length=30-60 minutes) ]
  40. Cmax of Bevacizumab [ Time Frame: 30 minutes after end of infusion on Day 1 of Cycles 1 and 2 (1 cycle=6 weeks) (infusion length=30-90 minutes) ]
  41. Cmin of Bevacizumab [ Time Frame: For Atezolizumab and Bevacizumab Arm: at First-line treatment discontinuation (up to approximately 2.75 years); For Crossover Arms: pre-infusion (0 hour) on Day 1 of Cycle 2 (1 cycle=6 weeks) (infusion length=30-90 minutes) ]
  42. M.D. Anderson Symptom Inventory (MDASI) Interference Score [ Time Frame: Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks) ]
    MDASI questionnaire comprises of 2 parts: symptoms (16 items), interference with daily life (6 items). Participants were asked to rate how much their symptoms interfered with general activity, mood, work, relations with other people, walking, and enjoyment of life during the last 24 hours. Each item in the interference score was answered on a scale of 0 (did not interfere) to 10 (interfered completely). The mean score of all 6 items was reported on the scale of 0 (did not interfere) to 10 (interfered completely).

  43. Brief Fatigue Inventory (BFI) Fatigue Level Score [ Time Frame: Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks) ]
    BFI questionnaire comprises of 2 parts: fatigue level (3 items), interference with daily life (1 item with 6 sub-items). Each items in the fatigue level score was answered on a scale of 0 (no fatigue) to 10 (as bad as you can imagine). The mean score of all 3 items was reported on the scale of 0 (no fatigue) to 10 (as bad as you can imagine).


Other Outcome Measures:
  1. EuroQoL 5 Dimension (EQ-5D) Questionnaire Score [ Time Frame: Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks) ]
    EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

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 (anti-CTLA-4), anti-programmed death-1 (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

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): NCT01984242


  Hide Study Locations
Locations
United States, Arizona
HonorHealth Research Institute - Pima Center
Scottsdale, Arizona, United States, 85258
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010
UCLA
Los Angeles, California, United States, 90024
University of California
San Francisco, California, United States, 94158
United States, Colorado
Univ Colorado Health Sci Ctr
Aurora, Colorado, United States, 80045
Rocky Mountain Cancer Ctr - Denver (Williams)
Denver, Colorado, United States, 80218
United States, Connecticut
Yale Uni School of Medicine; Section of Medical Oncology
New Haven, Connecticut, United States, 06510-3289
United States, District of Columbia
Georgetown U; Lombardi Comp Can
Washington, District of Columbia, United States, 20016-1468
United States, Florida
SCRI Florida Cancer Specialists South
Fort Myers, Florida, United States, 33916
Mayo Clinic-Jacksonville
Jacksonville, Florida, United States, 32224
Florida Cancer Specialist, North Region
Saint Petersburg, Florida, United States, 33705
United States, Illinois
The University of Chicago
Chicago, Illinois, United States, 60637
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Inst.
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
Karmanos Cancer Institute.
Detroit, Michigan, United States, 48201
United States, Nevada
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89128
United States, New York
Memorial Sloan-Kettering
New York, New York, United States
United States, Ohio
Oncology Hematology Care Inc
Cincinnati, Ohio, United States, 45242
Cleveland Clinic Foundation; Taussig Cancer Center
Cleveland, Ohio, United States, 44195
United States, Oregon
Oncology Associates of Oregon, P.C
Eugene, Oregon, United States, 97401
Northwest Cancer Specialists, P.C.
Tualatin, Oregon, United States, 97062
United States, Tennessee
Tennessee Oncology PLLC - Nashville (20th Ave)
Nashville, Tennessee, United States, 37203
Vanderbilt Medical Center
Nashville, Tennessee, United States, 37232-7610
United States, Texas
Texas Oncology-Baylor Sammons Cancer Center
Dallas, Texas, United States, 75246
Czechia
Fakultni nemocnice Olomouc
Olomouc, Czechia, 775 20
Fakultni nemocnice v Motole
Praha 5, Czechia, 150 06
Masarykova nemocnice Usti nad Labem
Ústí nad Labem, Czechia, 401 13
France
ICO Paul Papin; Oncologie Medicale.
Angers, France, 49055
Centre Oscar Lambret; Cancerologie Urologie Digestive
Lille, France, 59020
Centre Leon Berard; Departement Oncologie Medicale
Lyon, France, 69373
Hopital Saint Louis; Oncologie Medicale
Paris, France, 75475
Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale
Paris, France, 75908
CHU Bordeaux
Pessac, France, 33604
Institut Claudius Regaud; Departement Oncologie Medicale
Toulouse, France, 31059
Institut Gustave Roussy; Departement Oncologie Medicale
Villejuif, France, 94805
Germany
Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie
Hannover, Germany, 30625
Klinikum d.Universität München Campus Großhadern
München, Germany, 81377
Klinikum rechts der Isar der TU München; Klinikapotheke
München, Germany, 81675
Italy
Ospedale San Raffaele; Medical Oncology
Milano, Lombardia, Italy, 20132
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
Milano, Lombardia, Italy, 20133
Medical Oncology, Arezzo
Arezzo, Toscana, Italy, 52100
Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica
Siena, Toscana, Italy, 53100
Poland
Centrum Med. Ostrobramska NZOZ Magodent
Warszawa, Poland, 04-125
Romania
Prof. Dr. I. Chiricuta Institute of Oncology
Cluj Napoca, Romania, 400015
Medisprof SRL
Cluj-Napoca, Romania, 400058
Spitalul Judetean de Urgenta Satu Mare
Satu Mare, Romania, 440055
Spain
Clinica Universitaria de Navarra
Pamplona, Navarra, Spain, 31008
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 08035
Hospital Clinic de Barcelona. Unidad de Nuevas Terapias;Oncology Department
Barcelona, Spain, 08036
Hospital Univ 12 de Octubre
Madrid, Spain, 28041
Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal
Madrid, Spain, 28050
Hosp Clinico Univ Lozano Blesa
Zaragoza, Spain, 50009
United Kingdom
The Clatterbridge Cancer Ctr NHS Foundation Trust
Bebington, United Kingdom, CH63 4JY
Barts and the London NHS Trust.
London, United Kingdom, EC1A 7BE
Royal Marsden Hospital - London
London, United Kingdom, SW3 6JJ
Christie Hospital Nhs Trust; Medical Oncology
Manchester, United Kingdom, M2O 4BX
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01984242     History of Changes
Other Study ID Numbers: WO29074
2013-003167-58 ( EudraCT Number )
First Posted: November 14, 2013    Key Record Dates
Results First Posted: December 21, 2017
Last Update Posted: May 31, 2018
Last Verified: May 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