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
* This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug combination to learn whether the drug combination works in treating a specific disease. "Investigational" means that the drug combination is being studied. * The FDA (the U.S. Food and Drug Administration) has not approved PDR001 as a treatment for any disease. * The FDA has not approved dabrafenib and trametinib for your specific disease but it has been approved for other uses, whether alone as single agents, or given together as in this study. * This research study is studying a combination of drugs as a possible treatment for metastatic colorectal cancer characterized by BRAF V600E mutation. * All humans have a gene called BRAF which is responsible for sending signals to proteins called B-Raf inside of cells that help them grow. In some metastatic colorectal patients, this gene mutates and causes cancer cells to grow in uncontrolled ways. \--- Dabrafenib is a drug that is thought to inhibit the mutant BRAF activity, which may serve to slow or stop cell growth of metastatic colon cancer. * Mitogen-activated protein kinase (MAPK) is a pathway that helps to activate the BRAF mutated genes. The MAPK pathway is commonly found to be overactivated in BRAF mutated tumor cells. MEK (which refers to MAPK/ERK Kinase) enzymes are essential to the activity of the MAPK pathway. * Trametinib inhibits the MEK enzymes in order to shut down the MAPK pathway, thus blocking the pathway that helps the cancer cells grow uncontrollably. * PDR001 is a drug which binds to PD1 on immune cells and is believed to block binding of PD-L1 and PD-L2. PD-L1/PDL1 and PD-L2/PDL2 are often used by cancer cells and to escape the power of the body's immune system so that they cannot be fought. By blocking that binding of the molecules, the body's immune system may reach and fight the cancer cells. Researchers are hoping that administration of all three of these drugs may help anti-cancer activities work together to slow or stop the cancer growth and may help your own immune system damage or destroy the existing cancer cells.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Dabrafenib will be taken twice a day for 28 consecutive days .
Trametinib will be taken once a day for 28 consecutive days
PDR001 will be administered IV every 28 days
Massachusetts General Hosital Cancer Center
Boston, Massachusetts, United States
RECRUITINGDana Farber Cancer Institite
Boston, Massachusetts, United States
RECRUITINGOverall Response Rate
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.
Time frame: From the start of the treatment until disease progression/recurrence, up to approximately 5 years
Number of participants with grade 3, 4 and 5 adverse events
Adverse Events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE 4)
Time frame: From the start of treatment until 30 days after the last dose of a study drug, up to approximately 5 years
Progression Free Survival
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).
Time frame: From the date of randomization until disease progression or death due to any cause, up to approximately 5 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Disease Control Rate
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.
Time frame: From the start of the treatment until disease progression/recurrence, up to approximately 5 years
Duration of Response
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.
Time frame: From the first documented response until the time of disease progression, up to approximately 5 years
Overall Survival
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.
Time frame: From the date of randomization until the time of death, up to approximately 10 years
Mechanisms of response and resistance to dabrafenib, trametinib, and PDR001
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.
Time frame: Pre treatment and day 15