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Trial record 1 of 1 for:    NCT02420821
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A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma (RCC) (IMmotion151)

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ClinicalTrials.gov Identifier: NCT02420821
Recruitment Status : Active, not recruiting
First Posted : April 20, 2015
Results First Posted : October 3, 2018
Last Update Posted : November 28, 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 plus bevacizumab versus sunitinib in participants with inoperable, locally advanced, or metastatic 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-PD-L1 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 20, 2015
Actual Primary Completion Date : September 29, 2017
Estimated Study Completion Date : December 1, 2021


Arm Intervention/treatment
Experimental: Atezolizumab + Bevacizumab
Participants will receive both atezolizumab and bevacizumab until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression, withdrawal of consent, or death, whichever occurs first.
Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on Days 1 and 22 of each 42-day cycle.
Other Name: Tecentriq, MPDL3280A

Drug: Bevacizumab
Bevacizumab will be administered at a dose of 15 milligrams per kilogram (mg/kg) via IV infusion on Days 1 and 22 of each 42-day cycle.
Other Name: Avastin

Active Comparator: Sunitinib
Participants will receive sunitinib until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression, withdrawal of consent, or death, whichever occurs first.
Drug: Sunitinib
Sunitinib will be administered at a dose of 50 mg once daily, orally via capsule, on Day 1 through Day 28 of each 42-day cycle.
Other Name: Sutent




Primary Outcome Measures :
  1. Percentage of Participants With Disease Progression as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death From Any Cause in Programmed Death-Ligand 1 (PD-L1)-Selected Population [ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    Tumor response was assessed by the investigator according to RECIST v1.1. Disease Progression (PD) was defined as greater than or equal to (>/=) 20 percent (%) relative increase in the sum of diameters (SoD) of all target lesions (TLs), taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 millimeters (mm); >/=1 new lesion(s); and/or unequivocal progression of existing non-TLs.

  2. Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 in PD-L1-Selected Population [ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Participants with a PFS event who missed >/=2 scheduled assessments immediately prior to the PFS event were censored at the last tumor assessment prior to the missed visits. Median PFS was estimated by Kaplan-Meier method and 95% confidence interval (CI) was assessed using the method of Brookmeyer and Crowley.

  3. Percentage of Participants Who Died of Any Cause in ITT Population [ Time Frame: Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months) ]
    Percentage of participants who died of any cause was reported.

  4. Overall Survival (OS) in ITT Population [ Time Frame: Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months) ]
    OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.


Secondary Outcome Measures :
  1. Percentage of Participants Who Died of Any Cause in PD-L1-Selected Population [ Time Frame: Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months) ]
    Percentage of participants who died of any cause was reported.

  2. OS in PD-L1-Selected Population [ Time Frame: Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months) ]
    OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

  3. Percentage of Participants With PD as Determined by an Independent Review Committee (IRC) According to RECIST v1.1 or Death From Any Cause in ITT Population [ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    Tumor response was assessed by an IRC according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.

  4. PFS as Determined by an IRC According to RECIST v1.1 in ITT Population [ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    PFS was defined as the time from randomization to PD, as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

  5. Percentage of Participants With PD as Determined by an IRC According to RECIST v1.1 or Death From Any Cause in PD-L1-Selected Population [ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    Tumor response was assessed by an IRC according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.

  6. PFS as Determined by an IRC According to RECIST v1.1 in PD-L1-Selected Population [ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    PFS was defined as the time from randomization to PD, as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

  7. 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 in Objective Response Rate (ORR)-Evaluable Population [ Time Frame: Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    Tumor response was assessed by the investigator according to RECIST v1.1. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs and (if applicable) normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to less than (<) 10 mm. PR was defined as >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.

  8. Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 in DOR-Evaluable Population [ Time Frame: Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    DOR was defined as the time from the first occurrence of CR/PR to PD as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs and normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or maintenance of tumor marker level above the normal limits. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.

  9. Percentage of Participants With an Objective Response of CR or PR as Determined by an IRC According to RECIST v1.1 in ORR-Evaluable Population [ Time Frame: Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    Tumor response was assessed by an IRC according to RECIST v1.1. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs and (if applicable) normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR was defined as >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or (if applicable) maintenance of tumor marker level above the normal limits. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.

  10. DOR as Determined by an IRC According to RECIST v1.1 in DOR-Evaluable Population [ Time Frame: Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    DOR was defined as the time from the first occurrence of CR/PR to PD as determined by an IRC per RECIST v1.1, or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs and normalization of tumor marker level or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs (taking as reference the baseline SoD) or persistence of >/=1 non-TL(s) and/or maintenance of tumor marker level above the normal limits. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.

  11. Percentage of Participants With PD as Determined by the Investigator According to Immune-Modified RECIST or Death From Any Cause in ITT Population [ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    Tumor response was assessed by the investigator according to immune-modified RECIST. PD was defined as >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm.

  12. PFS as Determined by the Investigator According to Immune-Modified RECIST in ITT Population [ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    PFS was defined as the time from randomization to PD, as determined by the investigator per immune-modified RECIST or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

  13. Percentage of Participants With an Objective Response of CR or PR as Determined by the Investigator According to Immune-Modified RECIST in ORR-Evaluable Population [ Time Frame: Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    Tumor response was assessed by the investigator according to immune-modified RECIST. Objective response was defined as percentage of participants with a documented CR or PR. CR was defined as disappearance of all TLs/non-TLs or reduction in short axis of any pathological lymph nodes to <10 mm. PR was defined as >/=30% decrease in the SoD of TLs and all new measurable lesions (taking as reference the baseline SoD), in the absence of CR. The 95% CI was computed using Clopper-Pearson approach. Participants without any post-baseline tumor assessments were considered non-responders.

  14. DOR as Determined by the Investigator According to Immune-Modified RECIST in DOR-Evaluable Population [ Time Frame: Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    DOR was defined as the time from the first occurrence of CR/PR to PD as determined by the investigator per immune-modified RECIST or death from any cause, whichever occurred first. CR: disappearance of TLs/non-TLs or reduction in short axis of any pathological lymph nodes to <10 mm. PR: >/=30% decrease in the SoD of TLs and all new measurable lesions (taking as reference the baseline SoD), in the absence of CR. PD: >/=20% relative increase in the SoD of all TLs and all new measurable lesions, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm. Participants without PD or death after a CR/PR were censored at last tumor assessment. Participants without tumor assessments after a CR/PR were censored at first CR/PR + 1 day. Median DOR was estimated by Kaplan-Meier method and 95% CI by the method of Brookmeyer and Crowley.

  15. Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in ITT Population [ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.

  16. PFS as Determined by the Investigator According to RECIST v1.1 in ITT Population [ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1 or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Participants with a PFS event who missed >/=2 scheduled assessments immediately prior to the PFS event were censored at the last tumor assessment prior to the missed visits. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

  17. Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in Participants With Sarcomatoid Histology [ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    Tumor response was assessed by the investigator according to RECIST v1.1. PD was defined as >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs.

  18. PFS as Determined by the Investigator According to RECIST v1.1 in Participants With Sarcomatoid Histology [ Time Frame: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months) ]
    PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1 or death from any cause, whichever occurred first. PD: >/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of >/=5 mm; >/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Median PFS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

  19. Percentage of Participants Who Died of Any Cause in Participants With Sarcomatoid Histology [ Time Frame: Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months) ]
    Percentage of participants who died of any cause was reported.

  20. OS in Participants With Sarcomatoid Histology [ Time Frame: Baseline until death from any cause (until data cut-off date 29 September 2017, up to approximately 27 months) ]
    OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

  21. Change From Baseline in Symptom Interference as Determined by M.D. Anderson Symptom Inventory (MDASI) Part II Score [ Time Frame: Baseline (Day 1 Cycle 1); Day 22 Cycle 1; Day 1 and 22 of every cycle from Cycle 2 up to Cycle 19; Cycle length = 42 days ]
    The MDASI is a cancer-related, multi-symptom, valid, and reliable self-report questionnaire that comprises of 23 items and two subscales: symptom severity (17 items) and symptom interference (6 items). In Part II, participants were asked to rate how much the symptoms have interfered with 6 areas of function (general activity, walking, work, mood, relations with other people, and enjoyment of life) in the last 24 hours. Each item was rated on a scale of 0 (does not interfere) to 10 (interfered completely) and total Part II score was calculated as an average of 6-item scores. Repeated measures model-estimated least-squares (LS) mean score for changes from baseline is reported at each timepoint, where a negative value indicates improvement. Here, 'Number Analyzed' = number of participants evaluable at specified time point.

  22. Change From Baseline in Symptom Severity as Determined by MDASI Part I Score [ Time Frame: Baseline; End of Treatment (EoT) visit (up to approximately 27 months) ]
    The MDASI is a cancer-related, multi-symptom, valid, and reliable self-report questionnaire that comprises of 23 items and two subscales: symptom severity (17 items) and symptom interference (6 items). In Part I, participants were asked to rate how severe the symptoms (pain, fatigue, nausea, disturbed sleep, feeling of being distressed, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, feeling sad, vomiting, numbness or tingling, rash/skin changes, headache, mouth/throat sores, and diarrhea) were when "at their worst" in the last 24 hours. Each item was rated on a scale of 0 (not present) to 10 (as bad as you can imagine). Mixed-effects model-estimated LS mean score for change from baseline at the end-of treatment is reported for each item, where a negative value indicates improvement.

  23. Change From Baseline in Symptom Severity as Determined by Brief Fatigue Inventory (BFI) Interference Scale Score [ Time Frame: Baseline (Day 1 Cycle 1); every week for first 12 weeks, Days 1 and 22 of each cycle (Cycle 3 up to 19), within 30 days of PD (up to 27 months), at EoT (up to 27 months) and at 6, 12, 24, and 36 weeks after EoT (overall up to 27 months); 1 cycle=42 days ]
    The BFI is a valid and reliable self-report questionnaire used to assess the severity and impact of cancer-related fatigue. BFI interference subscale (6 items) assessed the impact of fatigue on global domains (general activity, mood, walking ability, normal work, relations with other people, and enjoyment of life) in the last 24 hours. Each item was rated on a scale of 0 (does not interfere) to 10 (interfered completely). Change from baseline in the mean score of all 6 items at each timepoint is reported, where a negative value indicates improvement.

  24. Change From Baseline in Symptom Severity as Determined by BFI Worst Fatigue Item [ Time Frame: Baseline (Day 1 Cycle 1); every week for first 12 weeks, Days 1 and 22 of each cycle (Cycle 3 up to 19), within 30 days of PD (up to 27 months), at EoT (up to 27 months) and at 6, 12, 24, and 36 weeks after EoT (overall up to 27 months); 1 cycle=42 days ]
    The BFI is a valid and reliable self-report questionnaire used to assess the severity and impact of cancer-related fatigue. BFI worst fatigue item assessed the severity of fatigue at its worst in the last 24 hours. The item was rated on a scale of 0 (not present) to 10 (as bad as you can imagine). Change from baseline in the score at each time point is reported, where a negative value indicates improvement.

  25. Change From Baseline in Treatment Side Effects Burden as Determined by Functional Assessment of Cancer Therapy Kidney Symptom Index (FKSI-19) General Population 5 (GP5) Item Score [ Time Frame: Day 1 and 22 of every cycle (Baseline = Day 1 Cycle 1) up to Cycle 19; Cycle length = 42 days ]
    The FKSI-19 is a 19-item tool designed to assess the most important symptoms and concerns related to treatment effectiveness in advanced kidney cancer. The FKSI-19 GP5 item (bothered by the side effect of treatment) assessed side effects burden in the past 7 days on a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). Repeated measures model-estimated LS mean score for changes from baseline is reported at each timepoint, where a negative value indicates improvement.

  26. Number of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab [ Time Frame: Baseline (Predose [Hour 0] at Day 1 Cycle 1); Post-Baseline (Predose at Cycles 2, 4, and 8, and every eight cycles thereafter up to EoT [up to approximately 27 months] and 120 days after EoT [up to approximately 27 months]) (Cycle length=42 days) ]
    The number of participants with "Treatment-induced ATAs" and "Treatment-enhanced ATA" against atezolizumab at any time during or after treatment was reported. Treatment-induced ATA = a participant with negative or missing Baseline ATA result(s) and at least one positive post-Baseline ATA result. Treatment-enhanced ATA = a participant with positive ATA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result. Here, 'Overall Number of Participants Analyzed' = number of participants with a non-missing baseline ATA sample; 'Number Analyzed' = number of participants with a non-missing ATA sample at indicated timepoint.

  27. Number of Participants With ATAs Against Bevacizumab [ Time Frame: Baseline (Predose [Hour 0] at Day 1 Cycle 1); Post-Baseline (Predose at Cycle 3, at EoT [up to approximately 27 months] and at 120 days after EoT [up to approximately 27 months]) (Cycle length=42 days) ]
    The number of participants with "Treatment-induced ATAs" and "Treatment-enhanced ATA" against bevacizumab at any time during or after treatment was reported. Treatment-induced ATA = a participant with negative or missing Baseline ATA result(s) and at least one positive post-Baseline ATA result. Treatment-enhanced ATA = a participant with positive ATA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result.

  28. Maximum Observed Serum Concentration (Cmax) for Atezolizumab [ Time Frame: 30 minutes after the end of bevacizumab infusion (atezolizumab infusion duration: 30-60 min; bevacizumab infusion duration: 30-90 minutes) on Day 1 of Cycle 1 (Cycle length = 42 days) ]
    Cmax for atezolizumab was estimated from plasma concentration versus time data.

  29. Minimum Observed Serum Concentration (Cmin) for Atezolizumab [ Time Frame: Predose (Hour 0) on Day 22 of Cycle 1; predose (Hour 0) on Day 1 of Cycles 2; Cycle length = 42 days ]
    Cmin for atezolizumab was estimated from plasma concentration versus time data.

  30. Cmax for Bevacizumab [ Time Frame: 30 minutes after the end of bevacizumab infusion (atezolizumab infusion duration: 30-60 min; bevacizumab infusion duration: 30-90 minutes) on Day 1 of Cycle 1 (Cycle length = 42 days) ]
    Cmax for bevacizumab was estimated from plasma concentration versus time data.

  31. Cmin for Bevacizumab [ Time Frame: Pre-dose (Hour 0) on Day 1 of Cycle 3 (Cycle length = 42 days) ]
    Cmin for bevacizumab was estimated from plasma concentration versus time data.



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:

  • 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 (for influenza vaccination participants must agree not to receive live, attenuated influenza vaccine within 4 weeks prior to treatment, during treatment or within 5 months following the last dose)
  • 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


  Hide Study Locations
Locations
United States, Arizona
University of Arizona Cancer Center
Tucson, Arizona, United States, 85719
United States, California
University of California at Irvine Medical Center; Department of Oncology
Orange, California, United States, 92868
University of California
San Francisco, California, United States, 94158
United States, Colorado
University of Colorado; Anschutz Cancer Pavilion
Aurora, Colorado, United States, 80045
Rocky Mountain Cancer Center; Medical Oncology
Denver, Colorado, United States, 80218
United States, District of Columbia
Georgetown U; Lombardi Comp Can
Washington, District of Columbia, United States, 20016-1468
United States, Florida
Lynn Cancer Institute/Boca Raton Regional Hospital
Boca Raton, Florida, United States, 33486
Florida Cancer Specialists - Port Charlotte
Port Charlotte, Florida, United States, 33980
Florida Cancer Specialist, North Region
Saint Petersburg, Florida, United States, 33705
Florida Cancer Specialists
West Palm Beach, Florida, United States, 33401
United States, Georgia
Piedmont Cancer Institute, PC
Atlanta, Georgia, United States, 30318
Central Georgia Cancer Care PC
Macon, Georgia, United States, 31201
Northwest Georgia Oncology Centers PC - Marietta
Marietta, Georgia, United States, 30060
United States, Illinois
The University of Chicago
Chicago, Illinois, United States, 60637
United States, Kentucky
Norton Cancer Institute
Louisville, Kentucky, United States, 40202
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, Nevada
Comprehensive Cancer Centers of Nevada - Eastern Avenue
Las Vegas, Nevada, United States, 89169
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
New York Oncology Hematology,P.C.-Albany
Albany, New York, United States, 12208
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
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
Compass Oncology, The Northwest Cancer Specialists - Compass Oncology Tualatin
Tualatin, Oregon, United States, 97062
United States, Pennsylvania
Allegheny Cancer Center
Pittsburgh, Pennsylvania, United States, 15212
United States, Tennessee
SCRI Tennessee Oncology Chattanooga
Chattanooga, Tennessee, United States, 37404
Sarah Cannon Cancer Center and Research Institute
Nashville, Tennessee, United States, 37203
Vanderbilt Univ Medical Ctr
Nashville, Tennessee, United States, 37232
United States, Texas
Texas Oncology-Baylor Sammons Cancer Center
Dallas, Texas, United States, 75246
The Center for Cancer and Blood Disorders - Fort Worth
Fort Worth, Texas, United States, 76104
United States, Virginia
Oncology and Hematology Associates of SW Virginia-Raonoke
Roanoke, Virginia, United States, 24014
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Australia, New South Wales
Lifehouse
Camperdown, New South Wales, Australia, 2050
Macquarie University Hospital
Sydney, New South Wales, Australia, 2109
Calvary Mater Newcastle; Medical Oncology
Waratah, New South Wales, Australia, 2298
Australia, Queensland
Icon Cancer Foundation
South Brisbane, Queensland, Australia, 4101
Australia, South Australia
Ashford Cancer Center Research
Kurralta Park, South Australia, Australia, 5037
Australia, Victoria
Austin Hospital; Medical Oncology
Heidelberg, Victoria, Australia, 3084
Australia, Western Australia
St John of God Hospital
Murdoch, Western Australia, Australia, WA6150
Bosnia and Herzegovina
University Clinical Centre of the Republic of Srpska
Banja Luka, Bosnia and Herzegovina, 78000
Brazil
Hospital de Caridade de Ijui; Oncologia
Ijui, RS, Brazil, 98700-000
Santa Casa de Misericordia de Porto Alegre
Porto Alegre, RS, Brazil, 90020-090
Hospital Sao Lucas - PUCRS
Porto Alegre, RS, Brazil, 90610-000
Instituto do Cancer do Estado de Sao Paulo - ICESP
Sao Paulo, SP, Brazil, 01246-000
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre; Oncology
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
Royal Victoria Hospital
Barrie, Ontario, Canada, L4M 6M2
Hamilton Health Sciences - Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
London Regional Cancer Centre
London, Ontario, Canada, N6A 4L6
Lakeridge Health Oshawa; Oncology
Oshawa, Ontario, Canada, L1G 2B9
The Ottawa Hospital Cancer Centre; Oncology
Ottawa, Ontario, Canada, K1H 8L6
Sunnybrook Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
Montreal, Quebec, Canada, H3T 1E2
Canada
Centre Hospitalier universitaire de Québec/ Hotel Dieu de Québec
Quebec, Canada, G1R 3S1
Czechia
Masarykuv onkologicky ustav
Brno, Czechia, 656 53
Fakultni nemocnice Olomouc; Onkologicka klinika
Olomouc, Czechia, 779 00
Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika
Praha 2, Czechia, 128 08
Thomayerova nemocnice
Praha 4 - Krc, Czechia, 140 59
Denmark
Aarhus Universitetshospital; Kræftafdelingen
Aarhus N, Denmark, 8200
Herlev Hospital; Onkologisk afdeling
Herlev, Denmark, 2730
Odense Universitetshospital, Onkologisk Afdeling R
Odense C, Denmark, 5000
France
ICO Paul Papin; Oncologie Medicale.
Angers, France, 49055
Hopital Saint Andre; Oncologie 2
Bordeaux, France, 33075
Centre Francois Baclesse; Urologie Gynecologie
Caen, France, 14076
Centre Oscar Lambret
Lille, France, 59020
Centre Léon Bérard
Lyon, France, 69373
Institut Paoli Calmettes; Oncologie Medicale
Marseille, France, 13273
Centre D'Oncologie de Gentilly; Oncology
Nancy, France, 54100
APHP - Hospital Saint Louis
Paris, France, 75475
Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale
Paris, France, 75908
ICO - Site René Gauducheau
Saint Herblain, France, 44805
Institut Gustave Roussy; Departement Oncologie Medicale
Villejuif, France, 94805
Germany
Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Urologie
Dresden, Germany, 01307
Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung
Essen, Germany, 45122
Nationales Centrum für Tumorerkrankungen Heidelberg (NCT); Thoraxklinik Heidelberg
Heidelberg, Germany, 69120
Klinikum d.Universität München Campus Großhadern
München, Germany, 81377
Universitätsklinikum Tübingen; Klinik für Urologie
Tübingen, Germany, 72076
Italy
Az. Osp. Cardarelli; Divisione Di Oncologia
Napoli, Campania, Italy, 80131
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
Meldola, Emilia-Romagna, Italy, 47014
A.O. Universitaria Policlinico Di Modena; Oncologia
Modena, Emilia-Romagna, Italy, 41100
Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica
Roma, Lazio, Italy, 00152
Irccs Ospedale San Raffaele;Oncologia Medica
Milano, Lombardia, Italy, 20132
Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
Milano, Lombardia, Italy, 20162
Fondazione IRCCS Policlinico San Matteo, Oncologia
Pavia, Lombardia, Italy, 27100
Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia
Arezzo, Toscana, Italy, 52100
Japan
Nagoya University Hospital; Urology
Aichi, Japan, 466-8560
Chiba Cancer Center
Chiba, Japan, 260-8717
Kyushu University Hospital
Fukuoka, Japan, 812-8582
Gunma University Hospital
Gunma, Japan, 371-8511
Hokkaido University Hospital
Hokkaido, Japan, 060-8648
University of Tsukuba Hospital; Urology
Ibaraki, Japan, 305-8576
Iwate Medical University Hospital
Iwate, Japan, 020-8505
Yokohama City University Hospital
Kanagawa, Japan, 236-0004
Kitasato University Hospital
Kanagawa, Japan, 252-0375
Kumamoto University Hospital
Kumamoto, Japan, 860-8556
Niigata University Medical & Dental Hospital
Niigata, Japan, 951-8520
Okayama University Hospital
Okayama, Japan, 700-8558
Osaka International Cancer Institute; Urology
Osaka, Japan, 541-8567
Osaka City University Hospital
Osaka, Japan, 545-8586
Osaka University Hospital
Osaka, Japan, 565-0871
Kindai University Hospital
Osaka, Japan, 589-8511
Saitama Medical University International Medical Center
Saitama, Japan, 350-1298
Tokushima University Hospital
Tokushima, Japan, 770-8503
Toranomon Hospital
Tokyo, Japan, 105-8470
Tokyo Medical & Dental University Hospital
Tokyo, Japan, 113-8519
Nippon Medical School Hospital
Tokyo, Japan, 113-8603
The Cancer Institute Hospital, JFCR; Urology
Tokyo, Japan, 135-8550
Keio University Hospital
Tokyo, Japan, 160-8582
Tokyo Women's Medical University
Tokyo, Japan, 162-0054
Korea, Republic of
Chungnam National University Hospital
Daejeon, Korea, Republic of, 35015
National Cancer Center
Gyeonggi-do, Korea, Republic of, 10408
Seoul National University Bundang Hospital
Gyeonggi-do, Korea, Republic of, 13620
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Severance Hospital, Yonsei University Health System; Pharmacy
Seoul, Korea, Republic of, 03722
Asan Medical Center
Seoul, Korea, Republic of, 05505
Samsung Medical Center
Seoul, Korea, Republic of, 6351
Mexico
Cancerología
Queretaro, Mexico, 76090
Centro Oncologico Estatal ISSEMYM
Toluca, Mexico, 50180
Poland
Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii
Bydgoszcz, Poland, 85-796
Wojewódzki Szpital Specjalistyczny im. M. Kopernika; Oddział Chemioterapii
Lodz, Poland, 93-513
Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli
Lublin, Poland, 20-090
Szpital Kliniczny; Przemienienia Panskiego;Uniwersytetu Medyczny im.; Karola Marcinkowskiego w Pozna
Poznan, Poland, 60-569
Saint Elizabeth's Hospital
Warsaw, Poland, 02-616
Centrum Med. Ostrobramska NZOZ Magodent
Warszawa, Poland, 04-125
Russian Federation
ALTAI REGIONAL ONCOLOGICAL CENTER; "Nadezhda" Clinic
Barnaul, Altaj, Russian Federation, 656049
GBUZ Nizhegorodskay Region: Clinical Diagnostic Center
Nizhni Novgorod, Niznij Novgorod, Russian Federation, 603001
P.A. Herzen Oncological Inst. ; Oncology
Moscow, Russian Federation, 125284
Moscow city oncology hospital #62 of Moscow Healthcare Department
Moscow, Russian Federation, 143423
Singapore
National University Hospital
Singapore, Singapore, 119074
National Cancer Centre; Medical Oncology
Singapore, Singapore, 169610
Oncocare Cancer Centre
Singapore, Singapore, 258499
Spain
Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
Sabadell, Barcelona, Spain, 08208
Hospital Universitario Reina Sofia; Servicio de Oncologia
Córdoba, Cordoba, Spain, 14004
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Barcelona, Spain, 08035
Hospital Clínic i Provincial; Servicio de Oncología
Barcelona, Spain, 08036
Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia
Barcelona, Spain, 08041
Hospital Duran i Reynals; Oncologia
Barcelona, Spain, 08907
Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
Madrid, Spain, 28007
Hospital Ramon y Cajal; Servicio de Oncologia
Madrid, Spain, 28034
Hospital Universitario 12 de Octubre; Servicio de Oncologia
Madrid, Spain, 28041
Hospital Universitario Virgen del Rocio; Servicio de Oncologia
Sevilla, Spain, 41013
Taiwan
Taichung Veterans General Hospital; Division of Urology
Taichung, Taiwan, 407
National Taiwan Uni Hospital; Dept of Oncology
Taipei, Taiwan, 100
Chang Gung Medical Foundation-Linkou, Urinary Oncology
Taoyuan, Taiwan, 333
Thailand
Chulalongkorn Hospital; Medical Oncology
Bangkok, Thailand, 10330
Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
Bangkok, Thailand, 10400
Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
Bangkok, Thailand, 10700
Maharaj Nakorn Chiangmai Hospital; Department of Surgery/ Urology unit
Chiangmai, Thailand, 50200
Prince of Songkla Uni ; Unit of Medical Oncology
Songkhla, Thailand, 90110
Turkey
Hacettepe University Medical Faculty
Ankara, Turkey, 06100
Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department
Edirne, Turkey, 22770
Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology
Istanbul, Turkey, 34300
United Kingdom
Clatterbridge Cancer Centre
Bebington, United Kingdom, CH63 4JY
Queen Elizabeth Hospital
Birmingham, United Kingdom, B15 2TH
Royal Blackburn Hospital
Blackburn, United Kingdom, BB2 3HH
Addenbrookes Nhs Trust; Oncology Clinical Trials Unit
Cambridge, United Kingdom, CB2 0QQ
Barts Health NHS Trust - St Bartholomew's Hospital
London, United Kingdom, EC1A 7BE
Royal Free Hospital; Dept of Oncology
London, United Kingdom, NW3 2QG
Royal Marsden Hospital; Dept of Med-Onc
London, United Kingdom, SW3 6JJ
Christie Hospital Nhs Trust; Medical Oncology
Manchester, United Kingdom, M2O 4BX
Churchill Hospital; Oxford Cancer and Haematology Centre
Oxford, United Kingdom, OX3 7LJ
Southampton General Hospital; Medical Oncology
Southampton, United Kingdom, SO16 6YD
Royal Marsden Hospital; Dept of Medical Oncology
Sutton, United Kingdom, SM2 5PT
Singleton Hospital; Pharmacy Department
Swansea, United Kingdom, SA2 8QA
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  Study Documents (Full-Text)

Documents provided by 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
Results First Posted: October 3, 2018
Last Update Posted: November 28, 2018
Last Verified: November 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