This research study is studying a combination of drugs as a possible treatment for metastatic colorectal cancer characterized by BRAF V600E mutation. The names of the study drugs involved in this study are: - Dabrafenib - Trametinib - PDR001
Name: Dabrafenib
Description: Dabrafenib will be taken twice a day for 28 consecutive days .Type: DrugPDR001, Dabrafenib, Trametinib
Name: Trametinib
Description: Trametinib will be taken once a day for 28 consecutive daysType: DrugPDR001, Dabrafenib, Trametinib
Name: PDR001
Description: PDR001 will be administered IV every 28 daysType: DrugPDR001, Dabrafenib, Trametinib
Description: The participants best overall response will be assessed using RECIST 1.1 criteria Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measure: Overall Response Rate Time: From the start of the treatment until disease progression/recurrence, up to approximately 5 yearsDescription: Adverse Events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE 4)
Measure: Number of participants with grade 3, 4 and 5 adverse events Time: From the start of treatment until 30 days after the last dose of a study drug, up to approximately 5 yearsDescription: Progression free survival is measured from the date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. Progression will be assessed using RECIST 1.1 Criteria. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Measure: Progression Free Survival Time: From the date of randomization until disease progression or death due to any cause, up to approximately 5 yearsDescription: The number of participants that achieve either a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) per RECIST 1.1 Criteria. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measure: Disease Control Rate Time: From the start of the treatment until disease progression/recurrence, up to approximately 5 yearsDescription: The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started, or death due to any cause. Participants without events reported are censored at the last disease evaluation). Response is assessed using RECIST 1.1 Criteria.
Measure: Duration of Response Time: From the first documented response until the time of disease progression, up to approximately 5 yearsDescription: Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive.
Measure: Overall Survival Time: From the date of randomization until the time of death, up to approximately 10 yearsDescription: Using multiplexed immune IF and RNAseq, assess the change in immune microenvironment between pre-treatment and day 15 on-treatment biopsies Using serial cfDNA analyses, monitor response and define mechanisms of resistance to this therapy.
Measure: Mechanisms of response and resistance to dabrafenib, trametinib, and PDR001 Time: Pre treatment and day 15Single Group Assignment
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Dabrafenib + Trametinib + PDR001 In Colorectal Cancer This research study is studying a combination of drugs as a possible treatment for metastatic colorectal cancer characterized by BRAF V600E mutation. --- V600E ---
Using multiplexed immune IF and RNAseq, assess the change in immune microenvironment between pre-treatment and day 15 on-treatment biopsies Using serial cfDNA analyses, monitor response and define mechanisms of resistance to this therapy.. Inclusion Criteria: - Participants must have histologically or cytologically confirmed metastatic colorectal cancer and a documented BRAF V600E mutation by a CLIA-certified laboratory test and must be wild-type for KRAS and NRAS. --- V600E ---
Inclusion Criteria: - Participants must have histologically or cytologically confirmed metastatic colorectal cancer and a documented BRAF V600E mutation by a CLIA-certified laboratory test and must be wild-type for KRAS and NRAS. --- V600E ---
- This research study is studying a combination of drugs as a possible treatment for metastatic colorectal cancer characterized by BRAF V600E mutation. --- V600E ---