Phase II Study of Cobimetinib in Combination With Vemurafenib in Active Melanoma Brain Metastases (CoBRIM-B)
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|ClinicalTrials.gov Identifier: NCT02230306|
Recruitment Status : Terminated (closed due to slow accrual)
First Posted : September 3, 2014
Results First Posted : October 12, 2017
Last Update Posted : October 12, 2017
|Condition or disease||Intervention/treatment||Phase|
|Active Melanoma Brain Metastases||Drug: Cobimetinib Drug: Vemurafenib||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Cobimetinib in Combination With Vemurafenib in Active Melanoma Brain Metastases|
|Study Start Date :||February 2015|
|Actual Primary Completion Date :||March 2016|
|Actual Study Completion Date :||March 2016|
Experimental: Cobimetinib in Combination with Vemurafenib
Vemurafenib (960 mg twice a day) will be taken on Days 1 - 28 of each 28-day treatment cycle. The first dose of vemurafenib should be taken in the morning, and the second dose should be taken in the evening. Vemurafenib can be taken with or without a meal and should be taken with a glass of water.
Cobimetinib (60 mg once a day) will be taken on Days 1 - 21 of each 28-day treatment cycle. The cobimetinib tablet should be taken at approximately the same time each day in the morning with the vemurafenib dose, but no later than 4 hours after the scheduled time. Cobimetinib can be taken with or without a meal and should never be chewed, cut, or crushed and should be taken with a glass of water.
60mg once a day; will be taken on days 1-21 of each 28 day treatment cycle; will be taken in combination with Vemurafenib;
960mg twice a day; 28 day treatment cycle; will be taken in combination with Cobimetinib;
Other Name: Zelboraf
- Objective Intracranial Response (OIRR) [ Time Frame: Until disease progression, less than or equal to 5 years. ]Change in overall size of the sum of diameters from baseline of up to 5 intracranial target lesions in response to study treatment, achieved by individual patients.
- Overall Response [ Time Frame: Until disease progression, less than or equal to 5 years. ]Response to study treatment achieved by individual patients as indicated by an overall change in size of the sum of diameters from baseline of up to 5 intracranial target lesions and up to 5 extracranial target lesions.
- Progression-free Survival (PFS) [ Time Frame: Up to 5 years ]Time (number of months) from first documented evidence of overall Complete Response (CR) or Partial Response (PR) until time of first documented disease progression or death due to any cause (for individual patients). Progression as defined by RECIST 1.1 (Response Evaluation Criteria In Solid Tumors) is a ≥ 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5mm.
- Overall Survival (OS) [ Time Frame: Up to 5 years ]Number of months of survival for individual patients.
- Duration of Response [ Time Frame: Until disease progression, less than or equal to 5 years. ]Change in relative apparent diffusion coefficient (rADC) as measured by MRI as early predictor of response value/result for each patient
- Immune Modulation in Peripheral Blood [ Time Frame: Up to 5 years ]
- Early Markers of Progression in Peripheral Blood [ Time Frame: Up to 5 years ]
- Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br) [ Time Frame: Up to 5 years ]The Functional Assessment of Cancer Therapy-Brain (FACT-Br) is used to measure general quality of life (QOL) that reflects symptoms or problems associated with brain malignancies across 5 scales. The brain subscale is usually used along with the core (general) questionnaire that includes 27 items. The measure yields information about total QOL, as well as information about the dimensions of physical well-being, social/family well-being, emotional well being, functional well-being, and disease-specific concerns. Patients rate all 5 items using a five-point Likert scale ranging from 0 "not at all" to 4 "very much." Overall, higher ratings suggest higher QOL. Items are totaled to produce the following subscales, along with an overall QOL score: physical well-being (7 items); social/family well-being (7 items); emotional well-being (6 items); functional well-being (7 items); and concerns relevant to patients with brain tumors (23 items). Scoring range is 0-200.
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): NCT02230306
|United States, Connecticut|
|New Haven, Connecticut, United States, 06510|
|United States, Iowa|
|Mohammed Milhem, MD|
|Iowa City, Iowa, United States, 52242|
|United States, New York|
|Anna Pavlick, MD|
|New York, New York, United States, 10016|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Pennsylvania|
|Ravi Amaravadi, MD|
|Philadelphia, Pennsylvania, United States, 19104|
|UPMC Hillman Cancer Center|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Melissa Burgess, MD||University of Pittsburgh|
|Principal Investigator:||Richard Carvajal, MD||Memorial Sloan Kettering Cancer Center|
|Principal Investigator:||Anna Pavlick, MD||NYU Clinical Cancer Center|
|Principal Investigator:||Mohammed Milhem, MD||Univ of Iowa|
|Principal Investigator:||Ravi Amaravadi, MD||Univ of Pennsylvania|
|Principal Investigator:||Harriet Kluger, MD||Yale New Haven Hospital|