Vemurafenib and Cobimetinib Combination in BRAF Mutated Melanoma With Brain Metastasis (CONVERCE)
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|ClinicalTrials.gov Identifier: NCT02537600|
Recruitment Status : Completed
First Posted : September 1, 2015
Last Update Posted : January 27, 2020
|Condition or disease||Intervention/treatment||Phase|
|Malignant Melanoma||Drug: Cobimetinib + Vemurafenib combination treatment||Phase 2|
Patients will be enrolled into 3 cohorts:
- Cohort A : Neurologically asymptomatic patients who have not received prior local treatment ;
- Cohort B. Neurologically asymptomatic patients who have received prior local treatment;
- Cohort C. Neurologically symptomatic patients who have or have not received prior local treatment Every patients will be treated with Vemurafenib 960 mg PO, twice daily from D1 to D28, continuously
Cobimetinib 60 mg PO, once daily, from D1 to D21 - 1 cycle = 28 days
Treatment will be administered until progression (intracranial or extracranial), unacceptable toxicity, withdrawal of consent, death or decision of the treating investigator.
Patients who develop intracranial or extracranial progression and who, in the opinion of the treating investigator, could benefit from continuing treatment may continue treatment with vemurafenib and cobimetinib after approval from the principal investigator.
Patients who discontinue the study treatment will undergo an end-of-treatment visit 30 days after the last dose of vemurafenib and/or cobimetinib.
Patients who discontinue the study treatment for any reason other than progression (e.g. toxicity) must be followed up every 8 weeks unless they withdraw their consent.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||43 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Evaluation of Cobimetinib + Vemurafenib Combination Treatment in Patients With Brain Metastasis BRAFV600 Mutated Cutaneous Melanoma|
|Actual Study Start Date :||December 2015|
|Actual Primary Completion Date :||November 6, 2019|
|Actual Study Completion Date :||November 6, 2019|
Experimental: Cobimetinib + Vemurafenib combination
Every patients will be treated with :
Vemurafenib 1920 mg / day from day 1 to day 28 continuously Cobimetinib 60 mg / day from day 1 to day 21 One cycle = 28 days Intervention = Cobimetinib + Vemurafenib combination treatment. Only one arm.
Drug: Cobimetinib + Vemurafenib combination treatment
Patients will be treated from day 1 to day 28 with Vemurafenib and from day 1 to day 21 with Cobimetinib. Day 1 to Day 28 corresponds to one cycle of treatment.
- Complete or partial intracranial response rate in cohort A on the evaluation of each patient's best tumor response by the centralized review committee according to modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. [ Time Frame: From baseline up to 36 months ]
- Complete or partial intracranial response rates in cohorts B and C based on the evaluation of each patient's best tumor response by the centralized review committee according to modified RECIST 1.1 criteria. [ Time Frame: Up to 36 months ]
- Intracranial duration of response (DR) in cohorts A, B and C. [ Time Frame: Up to 36 months ]
- Overall response rate of cohorts A, B and C [ Time Frame: Up to 36 months ]
- Overall survival in cohorts A, B and C [ Time Frame: Up to 36 months ]
- Frequency of Adverse events [ Time Frame: Up to 36 months ]
- Overall duration of response (DR) in cohorts A, B and C. [ Time Frame: Up to 36 months ]
- Patient free survival in cohorts A, B and C [ Time Frame: Up to 36 months ]
- Ratio between cerebrospinal fluid concentration and plasmatic exposure of vemurafenib and cobimetinib [ Time Frame: At Day15 Cycle 1 ]
- BRAF mutation rate in circulating DNA tumor [ Time Frame: From baseline up to treatment stop or progression. An average of 8 cycles of treatment is expected. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02537600
|Principal Investigator:||Thierry Lesimple, MD||Centre Eugène Marquis|