Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Ph I Ipilimumab Vemurafenib Combo in Patients With v-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)

This study has been terminated.
(More than 2 of 6 patients treated experienced dose limiting toxicities.)
Sponsor:
Collaborator:
Roche-Genentech
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01400451
First received: July 21, 2011
Last updated: May 19, 2014
Last verified: May 2014
Results First Received: April 21, 2014  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Melanoma
Interventions: Drug: Ipilimumab (BMS-734016)
Biological: Vemurafenib

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Study initiated 30 Nov 2011; Primary Endpoint 25 April 2013. Dose-limiting toxicities (DLTs) observed early in dose escalation (Phase 1) portion of the study. The combination of drugs was not well tolerated, and a maximum tolerable dose was not attained so the study was closed to enrollment and Phase 2 portion not started.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
18 participants enrolled; 12 treated with study drug and 6 participants not treated because they no longer met study criteria. Data up to database cut off for primary endpoint are presented at this time.

Reporting Groups
  Description
3 mg/kg Ipilimumab + 960 mg Vemurafenib

Lead In Period: 28 Days of 720 mg or 960 mg vemurafenib orally twice daily (starting Day -27 or -13).

Combination Treatment (Induction of ipilimumab) Period: 3 milligrams per kilogram body weight (mg/kg) ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 960 mg vemurafenib orally twice daily throughout combination treatment.

3 mg/kg Ipilimumab + 720 mg Vemurafenib

Lead In Period: 28 Days of 720 mg or 960 mg vemurafenib orally twice daily (starting Day -27 or -13).

Combination Treatment (Induction of ipilimumab) Period: 3 milligrams per kilogram body weight (mg/kg) ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 720 mg vemurafenib orally twice daily throughout combination treatment.

720 mg Vemurafenib These participants were receiving 720 mg vemurafenib in the Lead in Period prior to starting ipilimumab but after the dose limiting toxicities (DLTs) were identified ipilimumab was not started. Due to disease stabilization, they continued on 720 mg vemurafenib alone orally twice daily. Note: the dose of vemurafenib could be escalated from 720 mg to 960 mg, at the investigator’s discretion.

Participant Flow for 2 periods

Period 1:   28 Day Lead In With Vemurafenib Alone
    3 mg/kg Ipilimumab + 960 mg Vemurafenib     3 mg/kg Ipilimumab + 720 mg Vemurafenib     720 mg Vemurafenib  
STARTED     6     4     2  
COMPLETED     6     4     2  
NOT COMPLETED     0     0     0  

Period 2:   Combination Treatment (or Intended)
    3 mg/kg Ipilimumab + 960 mg Vemurafenib     3 mg/kg Ipilimumab + 720 mg Vemurafenib     720 mg Vemurafenib  
STARTED     6     4     2 [1]
COMPLETED     0     0     1 [2]
NOT COMPLETED     6     4     1  
Withdrawal by Subject                 2                 1                 1  
Drug Toxicity                 0                 1                 0  
Adverse Event                 1                 0                 0  
Disease Progression                 3                 1                 0  
Dose-limiting toxicity                 0                 1                 0  
[1] Did not start Ipilimumab but remained on vemurafenib alone.
[2] One remained on treatment with vemurafenib alone through Day 171. Data currently outstanding.



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least one dose of study drug.

Reporting Groups
  Description
3 mg/kg Ipilimumab + 960 mg Vemurafenib

Lead In Period: 28 Days of 960 mg vemurafenib orally twice daily (starting Day -27 or -13).

Combination Treatment (Induction of ipilimumab) Period: 3 milligrams per kilogram body weight (mg/kg) ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1, plus 960 mg vemurafenib orally twice daily throughout combination treatment.

3 mg/kg Ipilimumab + 720 mg Vemurafenib

Lead In Period: 28 Days of 720 mg vemurafenib orally twice daily (starting Day -27 or -13).

Combination Treatment (Induction of ipilimumab) Period: 3 milligrams per kilogram body weight (mg/kg) ipilimumab intravenously once every 3 weeks for 4 weeks (Week 1, Week 4, Week 7, Week 10) starting on Day 1 plus 720 mg vemurafenib orally twice daily throughout combination treatment.

720 mg Vemurafenib These participants were receiving 720 mg vemurafenib in the Lead in Period prior to starting ipilimumab but after the dose limiting toxicities (DLTs) were identified, ipilimumab was not started. Due to disease stabilization, they continued on 720 mg vemurafenib alone orally twice daily.
Total Total of all reporting groups

Baseline Measures
    3 mg/kg Ipilimumab + 960 mg Vemurafenib     3 mg/kg Ipilimumab + 720 mg Vemurafenib     720 mg Vemurafenib     Total  
Number of Participants  
[units: participants]
  6     4     2     12  
Age  
[units: participants]
       
<=18 years     0     0     0     0  
Between 18 and 65 years     3     4     1     8  
>=65 years     3     0     1     4  
Gender  
[units: participants]
       
Female     3     2     1     6  
Male     3     2     1     6  
Race (NIH/OMB)  
[units: participants]
       
American Indian or Alaska Native     0     0     0     0  
Asian     0     0     0     0  
Native Hawaiian or Other Pacific Islander     0     0     0     0  
Black or African American     1     0     0     1  
White     5     4     2     11  
More than one race     0     0     0     0  
Unknown or Not Reported     0     0     0     0  
Region of Enrollment  
[units: participants]
       
United States     6     4     2     12  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   During the Lead In Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Vemurafenib Alone   [ Time Frame: From first vemurafenib dose to day prior to first ipilimumab dose (28 days); Patients who never progressed from Lead-in to combination treatmen (720 mg Alone): first dose to last dose + 90 days, up to Primary Endpoint Data Cut off, approximately 18 months ]

2.  Primary:   During the Combination Treatment Period: Number of Participants With Adverse Events (AEs), AEs Leading to Drug Discontinuation, Serious Adverse Events (SAEs), and Deaths in Participants Treated With Concurrent Ipilimumab and Vemurafenib   [ Time Frame: Combination drugs: Day 1 to last dose of drug + 90 days, up to data cut off for Primary Endpoint, approximately 18 months ]

3.  Primary:   Number of Participants With Hepatic Dose Limiting Toxicities (DLT) in Participants Treated With Concurrent Ipilimumab and Vemurafenib   [ Time Frame: Day 1 to last dose of drug + 90 days up to data cut off for Primary Endpoint, approximately 18 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
In Phase 1 of the study, MTD was not reached because more than 2 of 6 treated participants experienced DLTs with the combination therapy. Enrollments in Phase 1 were terminated and Phase 2 was not started so only overall safety was summarized.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


No publications provided by Bristol-Myers Squibb

Publications automatically indexed to this study:

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01400451     History of Changes
Other Study ID Numbers: CA184-161 ST, 2011-000906-22
Study First Received: July 21, 2011
Results First Received: April 21, 2014
Last Updated: May 19, 2014
Health Authority: United States: Food and Drug Administration