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Trial of Vemurafenib/Cobimetinib With or Without Bevacizumab in Patients With Stage IV BRAFV600 Mutant Melanoma

This study has been terminated.
(Slow accrual; toxicity; change in priorities)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01495988
First Posted: December 21, 2011
Last Update Posted: October 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Melanoma Research Foundation Breakthrough Consortium
Results First Submitted: May 30, 2017  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Melanoma
Metastatic Melanoma
Interventions: Drug: Vemurafenib
Drug: Bevacizumab
Drug: Cobimetinib

  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
Eight subjects were randomized under protocol v2.0 with the first subject enrolled on 8/13/2013. Two subjects were enrolled under protocol v4.0 with the first subject enrolled on 6/19/2015. The study was permanently closed on 6/13/2016. All subjects were recruited from Melanoma Research Foundation Breakthrough Consortium (MRFBC) clinical sites.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants has to meet the eligibility criteria prior to enrollment into the study.

Reporting Groups
  Description
Vemurafenib/Cobimetinib

Vemurafenib: Vemurafenib will be given at a dose of 960 mg, orally, 2X a day to all patients until disease progression, intolerable toxicity, patient request for discontinuation, or study termination by the sponsor.

Cobimetinib: Cobimetinib will be given at a dose of 60mg, orally, 1X a day to all patients for 21 days, then 7 days off, in a 28 day treatment cycle.

Patients will be assessed for toxicity every 4 weeks and be restaged for tumor response/progression every 8 weeks until week 48, then every 12 weeks thereafter. Patients will be followed until disease progression.

Vemurafenib/Cobimetinib + Bevacizumab

Vemurafenib: Vemurafenib will be given at a dose of 960 mg, orally, 2X a day to all patients until disease progression, intolerable toxicity, patient request for discontinuation, or study termination by the sponsor.

Bevacizumab: Patients assigned to the combination arm will also receive bevacizumab at 15mg/kg, intravenously, every 3 weeks.

Cobimetinib: Cobimetinib will be given at a dose of 60mg, orally, 1X a day to all patients for 21 days, then 7 days off, in a 28 day treatment cycle.

Patients will be assessed for toxicity every 4 weeks and be restaged for tumor response/progression every 8 weeks until week 48, then every 12 weeks thereafter. Patients will be followed until disease progression.

Vemurafenib

Vemurafenib will be given at a dose of 960 mg p.o. BID to all patients.

Patients will be assessed for toxicity every 3 or 6 weeks (depending on the specific toxicity) and be restaged for tumor response/progression every 6 weeks until week 48, then every 12 weeks thereafter.

Vemurafenib + Bevacizumab

Vemurafenib will be given at a dose of 960 mg p.o. BID to all patients.

Patients assigned to the combination arm will also receive bevacizumab 15 mg/kg every IV every 3 weeks.

Patients will be assessed for toxicity every 3 or 6 weeks (depending on the specific toxicity) and be restaged for tumor response/progression every 6 weeks until week 48, then every 12 weeks thereafter.


Participant Flow for 2 periods

Period 1:   Vem +/- Bev (Protocol v2.0)
    Vemurafenib/Cobimetinib   Vemurafenib/Cobimetinib + Bevacizumab   Vemurafenib   Vemurafenib + Bevacizumab
STARTED   0   0   5   3 
COMPLETED   0   0   5   3 
NOT COMPLETED   0   0   0   0 

Period 2:   Vem/Cobi +/- Bev (Protocol v4.0)
    Vemurafenib/Cobimetinib   Vemurafenib/Cobimetinib + Bevacizumab   Vemurafenib   Vemurafenib + Bevacizumab
STARTED   0   2   0   0 
COMPLETED   0   2   0   0 
NOT COMPLETED   0   0   0   0 



  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/Cobimetinib

Vemurafenib: Vemurafenib will be given at a dose of 960 mg, orally, 2X a day to all patients until disease progression, intolerable toxicity, patient request for discontinuation, or study termination by the sponsor.

Cobimetinib: Cobimetinib will be given at a dose of 60mg, orally, 1X a day to all patients for 21 days, then 7 days off, in a 28 day treatment cycle.

Patients will be assessed for toxicity every 4 weeks and be restaged for tumor response/progression every 8 weeks until week 48, then every 12 weeks thereafter. Patients will be followed until disease progression.

Vemurafenib/Cobimetinib + Bevacizumab

Vemurafenib: Vemurafenib will be given at a dose of 960 mg, orally, 2X a day to all patients until disease progression, intolerable toxicity, patient request for discontinuation, or study termination by the sponsor.

Bevacizumab: Patients assigned to the combination arm will also receive bevacizumab at 15mg/kg, intravenously, every 3 weeks.

Cobimetinib: Cobimetinib will be given at a dose of 60mg, orally, 1X a day to all patients for 21 days, then 7 days off, in a 28 day treatment cycle.

Patients will be assessed for toxicity every 4 weeks and be restaged for tumor response/progression every 8 weeks until week 48, then every 12 weeks thereafter. Patients will be followed until disease progression.

Vemurafenib

Vemurafenib will be given at a dose of 960 mg p.o. BID to all patients.

Patients will be assessed for toxicity every 3 or 6 weeks (depending on the specific toxicity) and be restaged for tumor response/progression every 6 weeks until week 48, then every 12 weeks thereafter.

Vemurafenib + Bevacizumab

Vemurafenib will be given at a dose of 960 mg p.o. BID to all patients.

Patients assigned to the combination arm will also receive bevacizumab 15 mg/kg every IV every 3 weeks.

Patients will be assessed for toxicity every 3 or 6 weeks (depending on the specific toxicity) and be restaged for tumor response/progression every 6 weeks until week 48, then every 12 weeks thereafter.

Total Total of all reporting groups

Baseline Measures
   Vemurafenib/Cobimetinib   Vemurafenib/Cobimetinib + Bevacizumab   Vemurafenib   Vemurafenib + Bevacizumab   Total 
Overall Participants Analyzed 
[Units: Participants]
 0   2   5   3   10 
Age 
[Units: Participants]
Count of Participants
         
<=18 years         0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Between 18 and 65 years         0   0.0%      1  20.0%      3 100.0%      4  40.0% 
>=65 years         2 100.0%      4  80.0%      0   0.0%      6  60.0% 
Sex: Female, Male 
[Units: Participants]
Count of Participants
         
Female         1  50.0%      1  20.0%      1  33.3%      3  30.0% 
Male         1  50.0%      4  80.0%      2  66.7%      7  70.0% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
         
Hispanic or Latino         0   0.0%      0   0.0%      1  33.3%      1  10.0% 
Not Hispanic or Latino         2 100.0%      5 100.0%      2  66.7%      9  90.0% 
Unknown or Not Reported         0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
         
American Indian or Alaska Native         0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Asian         0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Native Hawaiian or Other Pacific Islander         0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Black or African American         0   0.0%      0   0.0%      0   0.0%      0   0.0% 
White         2 100.0%      5 100.0%      3 100.0%      10 100.0% 
More than one race         0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Unknown or Not Reported         0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Region of Enrollment 
[Units: Participants]
Count of Participants
         
United States      2   5   3   10 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Maximum Tolerated Dose   [ Time Frame: Until MTD determined (up to 6 months) ]

2.  Primary:   Median Progression-free Survival   [ Time Frame: Time between randomization and disease progression (~10-15 months) ]

3.  Secondary:   Overall Survival   [ Time Frame: Time between randomization and death due to any cause (overall survival rates also to be assessed at 12 and 18 months) ]

4.  Secondary:   Response Rates   [ Time Frame: From time of randomization to time of disease progression (restaging for tumor response to occur every 8 wks until wk 48, then every 12 wks thereafter) ]

5.  Secondary:   Toxicity and Safety Profile   [ Time Frame: Until study completion ]

6.  Secondary:   Effects of the Addition of Bevacizumab on Tumor Angiogenesis, Resistance Mechanisms and Immune Function   [ Time Frame: Upon completion of the protocol (3 years) ]

7.  Secondary:   Correlate Blood Markers of B-RAFV600 Mutation With Treatment Efficacy   [ Time Frame: Upon completion of the protocol (3 years) ]


  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
The study was terminated prematurely on June 13, 2016. No further accrual to the study will occur.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.


Results Point of Contact:  
Name/Title: Damon Collie
Organization: The Emmes Corporation
phone: 301-251-1161
e-mail: dcollie@emmes.com



Responsible Party: Melanoma Research Foundation Breakthrough Consortium
ClinicalTrials.gov Identifier: NCT01495988     History of Changes
Other Study ID Numbers: ML27894
GEN-01 ( Other Identifier: MRFBC )
First Submitted: December 9, 2011
First Posted: December 21, 2011
Results First Submitted: May 30, 2017
Results First Posted: June 23, 2017
Last Update Posted: October 24, 2017