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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 : October 3, 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


  Show 165 Study Locations
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: October 3, 2018
Last Verified: September 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