Clinical Trial: Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025)

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Randomized, Open-Label, Phase 3 Study of Nivolumab (BMS-936558) vs. Everolimus in Subjects With Advanced or Metastatic Clear-Cell Renal Cell Carcinoma Who Have Received

Brief Summary: The purpose of the study is to compare the clinical benefit, as measured by duration of overall survival, of Nivolumab vs. Everolimus in subjects with advanced or metastatic clear-cell renal cell carcinoma who have received prior anti-angiogenic therapy

Detailed Summary:
Sponsor: Bristol-Myers Squibb

Current Primary Outcome: Overall Survival (OS) at Primary Endpoint [ Time Frame: Randomization until 398 deaths, up to May 2015 (approximately 30 months) ]

Original Primary Outcome:

• Overall survival [ Time Frame: Every clinic visit (every 2-4 weeks) up to 42 months ]
• Overall survival [ Time Frame: Every 3 months up to 5 years ]

Current Secondary Outcome:

• Investigator-assessed Objective Response Rate (ORR) at Primary Endpoint [ Time Frame: At 8 weeks post randomization, every 8 weeks for 12 months, and every 12 weeks until date of disease progression or death, up to May 2015 (approximately 30 months) ]
  ORR=number of participants with a best response of complete response (CR) or partial response (PR) divided by number of randomized participants. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR=At least a 30% decrease in the sum of diameters of target lesions, the baseline sum diameters used as reference. Tumor assessments began at 8 weeks following randomization and continued every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or death. CIs used Clopper and Pearson.
• Investigator-assessed Duration of Objective Response at Primary Endpoint [ Time Frame: From date of first response to date of disease progression or death or censoring if no progression or death occurred, up to May 2015 (approximately 30 months) ]
  Duration of objective response is defined as the time from first response (complete response, CR or partial response, PR) to the date of the first documented tumor progression as determined by the investigator (per RECIST 1.1 criteria or clinical) or death due to any cause, whichever occurred first. For participants who neither progress nor die, the duration of objective response were censored at the same time they were censored for the primary definition. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR=At least a 30% decrease in the sum of diameters of target lesions, the baseline sum diameters used as reference. Based on Kaplan-Meier Estimates.
• Investigator-assessed Time to Objective Response at Primary Endpoint [ Time Frame: Randomization to date of first response, up to May 2015 (approximately 30 months) ]
  Time to objective response is defined as the time from randomization to first response (complete response, CR or partial response, PR). CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.; PR=At least a 30% decrease in the sum of diameters of target lesions, the baseline sum diameters used as reference.
• Investigator-assessed Time of Progression-free Survival (PFS) at Primary Endpoint [ Time Frame: Randomization until 398 deaths, up to May 2015 (approximately 30 months) ]
  PFS=time from randomization to date of first documented tumor progression as determined by investigator (per RECIST 1.1 criteria or clinical) or death due to any cause, whichever occurred first. Participants who die without a reported prior progression and without subsequent anti-cancer therapy were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the date they were randomized. Participants who received any subsequent anti-cancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to or on initiation date of the subsequent anti-cancer therapy. Progressive disease: >=20% increase in sum of target lesion diameters and sum must show absolute increase of >=5mm; smallest sum on study as reference. Based on Kaplan-Meier Estimates.
• Overall Survival (OS) by Programmed Death-Ligand 1 (PD-L1) Expression Level at Primary Endpoint [ Time Frame: Randomization to date of death or date of last contact for patients without documentation of death, up to May 2015 (approximately 30 months) ]
  Quantifiable PD-L1 expression=percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay. If the PD-L1 staining could not be quantified it was classified as: indeterminate=tumor cell membrane staining hampered for reasons attributed to biology of tumor biopsy specimen and not due to improper sample preparation or handling; not evaluable=tumor biopsy specimen was not optimally collected or prepared. Not evaluable determined from H&E process before the tumor biopsy specimen was sent for evaluation or from H&E process during PD-L1 evaluation; baseline PD-L1 expression=if more than one tumor biopsy specimen was available, the most recently collected specimen with a quantifiable result. If all specimens for a given participant are either indeterminate or not evaluable, then the PD-L1 expression was considered indeterminate as long as at least one specimen is indeterminate. Otherwise, PD-L1 expression was considered not evaluable.
• Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events at Primary Endpoint [ Time Frame: Day of first dose to 30 days post final dose, up to May 2015 (approximately 30 months) ]
  Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious adverse event (SAE) defined: a medical event that at any dose results in dea
  
  

  Original Secondary Outcome:

  • Progression-free survival [ Time Frame: Disease assessments every 8 weeks after randomization for every 12 months then 12 weeks until progression of disease ]
  • Objective response rate [ Time Frame: Disease assessments every 8 weeks after randomization for every 12 months then 12 weeks until progression of disease ]
  • Duration of objective response [ Time Frame: Disease assessments every 8 weeks after randomization for every 12 months then 12 weeks until progression of disease ]
  • Duration of overall survival (OS) in Programmed death-ligand 1 (PD-L1) positive vs negative subgroups [ Time Frame: At every clinic visit (every 2-4 weeks) while on treatment and then every 3 months ]
  • Safety will be analyzed through the incidence of adverse events, serious adverse events [ Time Frame: Continuously throughout study treatment and up to 100 days from last dose ]
  • Safety will be analyzed through the incidence of laboratory abnormalities [ Time Frame: Continuously throughout study treatment and up to 100 days from last dose ]
  • Disease related symptom progression rate [ Time Frame: Baseline, Day 1 of each cycle (starting with cycle 2), then at first 2 follow-up visits ]

  
  
  Information By: Bristol-Myers Squibb
  

  Dates:
  Date Received: August 16, 2012
  Date Started: September 2012
  Date Completion: September 2018
  Last Updated: February 1, 2017
  Last Verified: April 2016
  

  

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