Phase II Safety Study of Vemurafenib Followed by Ipilimumab in Subjects With V600 BRAF Mutated Advanced Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01673854
First received: August 24, 2012
Last updated: June 20, 2016
Last verified: June 2016
Results First Received: July 3, 2015  
Study Type: Interventional
Study Design: Endpoint Classification: Safety Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Melanoma
Interventions: Drug: Ipilimumab
Biological: Vemurafenib

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 70 patients were enrolled, and 46 received treatment.

Reporting Groups
  Description
Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg Participants received vemurafenib, 960 mg, twice daily for 6 weeks (Vem1 Phase). After a washout period of 3-10 days, patients received ipilimumab, 10 mg/kg, every 3 weeks for a maximum of 4 doses. At Week 24, participants received ipilimumab, 10 mg/kg, every 12 weeks until disease progression or unacceptable toxicity. Patients who did not progress or have unacceptable toxicity in the Vem1 Phase were retreated with vemurafenib (Vem 2 Phase) at the last dose level identified at the end of the Vem1 Phase until disease progression or unacceptable toxicity.

Participant Flow for 3 periods

Period 1:   Vem 1 Phase (Vemurafenib, 960 mg)
    Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg  
STARTED     46  
COMPLETED     46  
NOT COMPLETED     0  

Period 2:   Ipilimumab Phase (Ipilimumab, 10 mg/kg)
    Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg  
STARTED     46  
COMPLETED     19  
NOT COMPLETED     27  
Disease progression                 7  
Study drug toxicity                 6  
Administrative Reason by Sponsor                 2  
Adverse event unrelated to study drug                 1  
Maximum clinical benefit                 1  
Death                 1  
Not identified                 2  
Not reported                 7  

Period 3:   Vem 2 Phase (Vemurafenib Retreatment)
    Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg  
STARTED     19  
COMPLETED     0  
NOT COMPLETED     19  
Disease progression                 12  
Study drug toxicity                 5  
Adverse event unrelated to study drug                 1  
Death                 1  



  Baseline Characteristics
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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.
No text entered.

Reporting Groups
  Description
Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg Participants received vemurafenib, 960 mg, twice daily for 6 weeks (Vem1 Phase). After a washout period of 3-10 days, patients received ipilimumab, 10 mg/kg, every 3 weeks for a maximum of 4 doses. At Week 24, participants received ipilimumab, 10 mg/kg, every 12 weeks until disease progression or unacceptable toxicity. Patients who did not progress or have unacceptable toxicity in the Vem1 Phase were retreated with vemurafenib (Vem 2 Phase) at the last dose level identified at the end of the Vem1 Phase until disease progression or unacceptable toxicity.

Baseline Measures
    Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg  
Number of Participants  
[units: participants]
  46  
Age  
[units: Years]
Mean (Standard Deviation)
  55.0  (14.20)  
Age  
[units: Years]
Median (Full Range)
  57.5  
  (18 to 81)  
Gender  
[units: Participants]
 
Female     9  
Male     37  
Race/Ethnicity, Customized  
[units: Participants]
 
White     42  
Other     4  
M-Stage at Study Entry [1]
[units: Participants]
 
M0     6  
M1A     8  
M1B     8  
M1C     24  
Disease Stage at Study Entry [2]
[units: Participants]
 
III     8  
IV     38  
Number of Disease Sites  
[units: Participants]
 
1     2  
2     8  
3     7  
4     4  
5 or more     25  
Eastern Cooperative Oncology Group (ECOG) Performance Status [3]
[units: Participants]
 
0     35  
1     11  
Time from Diagnosis of Advanced /Metastatic Melanoma to First Vem1 Phase Dose [4]
[units: Months]
Mean (Standard Deviation)
  4.96  (9.38)  
Time from Diagnosis of Advanced /Metastatic Melanoma to First Vem1 Phase Dose [5]
[units: Months]
Median (Full Range)
  1.86  
  (0.3 to 52.3)  
[1] M-stage=stage of metastases (M), based on criteria of the American Joint Committee on Cancer. M0=no metastases. M1A=metastases to skin, subcutaneous tissue, or distant lymph nodes. M1B=metastases to lung. M1C=metastases to all other visceral sites or distant metastases to any site combined with an elevated serum level of lactase dehydrogenase.
[2] Melanoma staging criteria: Stage III (A,B,C)=The tumor may be of any thickness and may or may not be ulcerated. The cancer cells have spread either to a few nearby lymph nodes or tissue just outside the tumor but not to the lymph nodes. Stage IV=The cancer cells have spread to the lymph nodes, other organs in the body, or areas far from the original site of the tumor. This is called metastatic melanoma.
[3] ECOG is a 6-item scale used to assess disease progression, daily functioning, and appropriate treatment and prognosis. Performance status is scored on a scale ranging from 0-5, with (best score) 0=fully active and able to carry on all predisease performance without restriction and (worst score) 5=death.
[4] Vem=vemurafenib.
[5] Vem=vemurafenib



  Outcome Measures
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1.  Primary:   Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Skin Adverse Events (AEs)   [ Time Frame: From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred first ]

2.  Secondary:   Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Gastrointestinal Adverse Events (AEs)   [ Time Frame: From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred first ]

3.  Secondary:   Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Hepatobiliary Adverse Events   [ Time Frame: From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred first ]

4.  Other Pre-specified:   Number of Participants Who Died, Who Died Due to Related Adverse Events (AEs), and With Related AEs, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to AEs and Related AEs, Immune-related (ir) AEs, and Serious irAEs   [ Time Frame: From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred first ]

5.  Other Pre-specified:   Number of Participants With Adverse Events (AEs) Grade 3-4, Related AEs Grade 3-4, Related Serious Adverse Events (SAEs) Grade 3-4, Immune-related (ir) AEs Grade 3-4, and Serious irAEs Grade 3-4   [ Time Frame: From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred first ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  More Information
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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



Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01673854     History of Changes
Other Study ID Numbers: CA184-240
2012‐002054‐24 ( EudraCT Number )
Study First Received: August 24, 2012
Results First Received: July 3, 2015
Last Updated: June 20, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board