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

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.
 
ClinicalTrials.gov Identifier: NCT01495988
Recruitment Status : Terminated (Slow accrual; toxicity; change in priorities)
First Posted : December 21, 2011
Results First Posted : June 23, 2017
Last Update Posted : October 24, 2017
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Melanoma Research Foundation Breakthrough Consortium

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
Enrollment 10
Recruitment Details 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 Participants has to meet the eligibility criteria prior to enrollment into the study.
Arm/Group Title Vemurafenib/Cobimetinib Vemurafenib/Cobimetinib + Bevacizumab Vemurafenib Vemurafenib + Bevacizumab
Hide Arm/Group Description

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: 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 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 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.

Period Title: Vem +/- Bev (Protocol v2.0)
Started 0 0 5 3
Completed 0 0 5 3
Not Completed 0 0 0 0
Period Title: Vem/Cobi +/- Bev (Protocol v4.0)
Started 0 2 0 0
Completed 0 2 0 0
Not Completed 0 0 0 0
Arm/Group Title Vemurafenib/Cobimetinib Vemurafenib/Cobimetinib + Bevacizumab Vemurafenib Vemurafenib + Bevacizumab Total
Hide Arm/Group Description

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: 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 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 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 of all reporting groups
Overall Number of Baseline Participants 0 2 5 3 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 2 participants 5 participants 3 participants 10 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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 2 participants 5 participants 3 participants 10 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)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 2 participants 5 participants 3 participants 10 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)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 2 participants 5 participants 3 participants 10 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  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 0 participants 2 participants 5 participants 3 participants 10 participants
2
 100.0%
5
 100.0%
3
 100.0%
10
 100.0%
1.Primary Outcome
Title Maximum Tolerated Dose
Hide Description To establish the maximum tolerated dose (MTD) of bevacizumab in combination with vemurafenib and cobimetinib.
Time Frame Until MTD determined (up to 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The trial was terminated prematurely during the phase Ib safety lead-in and outcome measures were not analyzed. MTD could not be determined.
Arm/Group Title Vemurafenib/Cobimetinib Vemurafenib/Cobimetinib + Bevacizumab Vemurafenib Vemurafenib + Bevacizumab
Hide Arm/Group Description:

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: 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 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 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.

Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Primary Outcome
Title Median Progression-free Survival
Hide Description To compare median progression-free survival (PFS) of patients with stage IV, BRAFV600E or BRAFV600K melanoma treated with vemurafenib/cobimetinib versus vemurafenib/cobimetinib and bevacizumab.
Time Frame Time between randomization and disease progression (~10-15 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The trial was terminated prematurely during the phase Ib safety lead-in and outcome measures were not analyzed due to significantly underpowered data and the MTD being undetermined.
Arm/Group Title Vemurafenib/Cobimetinib Vemurafenib/Cobimetinib + Bevacizumab Vemurafenib Vemurafenib + Bevacizumab
Hide Arm/Group Description:

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: 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 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 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.

Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Overall Survival
Hide Description Compare overall survival (OS) of patients with stage IV, BRAFV600E/K melanoma treated with vemurafenib/cobimetinib versus vemurafenib/cobimetinib and bevacizumab.
Time Frame Time between randomization and death due to any cause (overall survival rates also to be assessed at 12 and 18 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The trial was terminated prematurely during the phase Ib safety lead-in and outcome measures were not analyzed due to significantly underpowered data and the MTD being undetermined.
Arm/Group Title Vemurafenib/Cobimetinib Vemurafenib/Cobimetinib + Bevacizumab Vemurafenib Vemurafenib + Bevacizumab
Hide Arm/Group Description:

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: 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 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 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.

Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Response Rates
Hide Description Compare response rate (RR) of patients with stage IV, BRAFV600E/K melanoma treated with vemurafenib/cobimetinib versus vemurafenib/cobimetinib and bevacizumab.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
The trial was terminated prematurely during the phase Ib safety lead-in and outcome measures were not analyzed due to significantly underpowered data and the MTD being undetermined.
Arm/Group Title Vemurafenib/Cobimetinib Vemurafenib/Cobimetinib + Bevacizumab Vemurafenib Vemurafenib + Bevacizumab
Hide Arm/Group Description:

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: 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 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 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.

Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Toxicity and Safety Profile
Hide Description Describe the toxicity and safety profile of treatment with vemurafenib/cobimetinib versus vemurafenib/cobimetinib and bevacizumab in patients with stage IV, BRAFV600E/K melanoma.
Time Frame Until study completion
Hide Outcome Measure Data
Hide Analysis Population Description
The trial was terminated prematurely during the phase Ib safety lead-in and outcome measures were not analyzed due to significantly underpowered data and the MTD being undetermined.
Arm/Group Title Vemurafenib/Cobimetinib Vemurafenib/Cobimetinib + Bevacizumab Vemurafenib Vemurafenib + Bevacizumab
Hide Arm/Group Description:

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: 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 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 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.

Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Effects of the Addition of Bevacizumab on Tumor Angiogenesis, Resistance Mechanisms and Immune Function
Hide Description Perform a variety of correlative studies aimed at understanding the effects of vemurafenib/cobimetinib, and bevacizumab administration relative to vemurafenib/cobimetinib on tumor angiogenesis, resistance mechanisms and immune function.
Time Frame Upon completion of the protocol (3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The trial was terminated prematurely and outcome measures were not analyzed.
Arm/Group Title Vemurafenib/Cobimetinib Vemurafenib/Cobimetinib + Bevacizumab Vemurafenib Vemurafenib + Bevacizumab
Hide Arm/Group Description:

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: 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 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 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.

Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Correlate Blood Markers of B-RAFV600 Mutation With Treatment Efficacy
Hide Description Assess the effectiveness of blood reverse transcription polymerase chain reaction (RT-PCR) assay for BRAFV600 as a surrogate biomarker for tumor response and resistance in patients receiving vemurafenib/cobimetinib +/- bevacizumab.
Time Frame Upon completion of the protocol (3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The trial was terminated prematurely during the phase Ib safety lead-in and outcome measures were not analyzed due to significantly underpowered data and the MTD being undetermined.
Arm/Group Title Vemurafenib/Cobimetinib Vemurafenib/Cobimetinib + Bevacizumab Vemurafenib Vemurafenib + Bevacizumab
Hide Arm/Group Description:

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: 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 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 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.

Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Adverse Event data were collected from time of first study drug administration through 30 days following the last administration of study drug or study discontinuation/termination, whichever is earlier.
Adverse Event Reporting Description

Safety assessments will consist of monitoring and reporting the following adverse events (AEs):

  • Serious adverse events
  • Events that lead to drug discontinuation or interruption
  • All grade 3 and 4 toxicities
  • All deaths
  • Adverse events of special interest (AESI)
 
Arm/Group Title Vemurafenib/Cobimetinib Vemurafenib/Cobimetinib + Bevacizumab Vemurafenib Vemurafenib + Bevacizumab
Hide Arm/Group Description

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: 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 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 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.

All-Cause Mortality
Vemurafenib/Cobimetinib Vemurafenib/Cobimetinib + Bevacizumab Vemurafenib Vemurafenib + Bevacizumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/0      1/2 (50.00%)      5/5 (100.00%)      1/3 (33.33%)    
Hide Serious Adverse Events
Vemurafenib/Cobimetinib Vemurafenib/Cobimetinib + Bevacizumab Vemurafenib Vemurafenib + Bevacizumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/0      2/2 (100.00%)      3/5 (60.00%)      0/3 (0.00%)    
Cardiac disorders         
Myocardial Infarction  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 0/3 (0.00%)  0
Gastrointestinal disorders         
Incarcerated right femoral hernia  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 0/3 (0.00%)  0
Small Intestinal Obstruction  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 0/3 (0.00%)  0
Diarrhea  0/0  0 2/2 (100.00%)  2 0/5 (0.00%)  0 0/3 (0.00%)  0
Vomiting  0/0  0 1/2 (50.00%)  1 0/5 (0.00%)  0 0/3 (0.00%)  0
Retroperitoneal Hemorrhage  0/0  0 1/2 (50.00%)  1 0/5 (0.00%)  0 0/3 (0.00%)  0
General disorders         
Multi-Organ Failure  0/0  0 1/2 (50.00%)  1 0/5 (0.00%)  0 0/3 (0.00%)  0
Infections and infestations         
Sepsis  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 0/3 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Muscle Weakness Lower Limb  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 0/3 (0.00%)  0
Renal and urinary disorders         
Acute Kidney Injury  0/0  0 1/2 (50.00%)  1 0/5 (0.00%)  0 0/3 (0.00%)  0
1
Term from vocabulary, NCI CTCAE 4.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Vemurafenib/Cobimetinib Vemurafenib/Cobimetinib + Bevacizumab Vemurafenib Vemurafenib + Bevacizumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/0      2/2 (100.00%)      4/5 (80.00%)      3/3 (100.00%)    
Blood and lymphatic system disorders         
Anemia  0/0  0 0/2 (0.00%)  0 0/5 (0.00%)  0 1/3 (33.33%)  1
Cardiac disorders         
Myocardial Infarction  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 0/3 (0.00%)  0
Gastrointestinal disorders         
Diarrhea  0/0  0 2/2 (100.00%)  2 1/5 (20.00%)  1 1/3 (33.33%)  1
Incarcerated right femoral hernia  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 0/3 (0.00%)  0
Small Intestinal Obstruction  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 0/3 (0.00%)  0
Tooth Development Disorder  0/0  0 0/2 (0.00%)  0 0/5 (0.00%)  0 1/3 (33.33%)  1
Retroperitoneal Hemorrhage  0/0  0 1/2 (50.00%)  1 0/5 (0.00%)  0 0/3 (0.00%)  0
Vomiting  0/0  0 1/2 (50.00%)  1 0/5 (0.00%)  0 0/3 (0.00%)  0
General disorders         
Edema Limbs  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 0/3 (0.00%)  0
Fever  0/0  0 0/2 (0.00%)  0 0/5 (0.00%)  0 1/3 (33.33%)  1
Multi-Organ Failure  0/0  0 1/2 (50.00%)  1 0/5 (0.00%)  0 0/3 (0.00%)  0
Infections and infestations         
Sepsis  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 0/3 (0.00%)  0
Injury, poisoning and procedural complications         
Fall  0/0  0 1/2 (50.00%)  1 0/5 (0.00%)  0 0/3 (0.00%)  0
Investigations         
Lymphocyte Count Decreased  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 0/3 (0.00%)  0
Metabolism and nutrition disorders         
Hypoalbuminemia  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 0/3 (0.00%)  0
Hyponatremia  0/0  0 1/2 (50.00%)  1 1/5 (20.00%)  1 0/3 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Arthralgia  0/0  0 0/2 (0.00%)  0 0/5 (0.00%)  0 1/3 (33.33%)  1
Muscle Weakness Lower Limb  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 0/3 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Squamous Cell Carcinoma  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 0/3 (0.00%)  0
Nervous system disorders         
Headache  0/0  0 0/2 (0.00%)  0 0/5 (0.00%)  0 1/3 (33.33%)  1
Renal and urinary disorders         
Acute Kidney Injury  0/0  0 1/2 (50.00%)  1 0/5 (0.00%)  0 0/3 (0.00%)  0
Skin and subcutaneous tissue disorders         
Dry Skin  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 0/3 (0.00%)  0
Rash Acneiform  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 1/3 (33.33%)  1
Rash Maculo-Papular  0/0  0 0/2 (0.00%)  0 2/5 (40.00%)  2 2/3 (66.67%)  2
Unknown Rash  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 0/3 (0.00%)  0
Vascular disorders         
Hypertension  0/0  0 0/2 (0.00%)  0 1/5 (20.00%)  1 1/3 (33.33%)  1
1
Term from vocabulary, NCI CTCAE 4.0
The study was terminated prematurely on June 13, 2016. No further accrual to the study will occur.
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
Layout table for Results Point of Contact information
Name/Title: Damon Collie
Organization: The Emmes Corporation
Phone: 301-251-1161
EMail: dcollie@emmes.com
Layout table for additonal information
Responsible Party: Melanoma Research Foundation Breakthrough Consortium
ClinicalTrials.gov Identifier: NCT01495988    
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