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Abbreviated MAPK Targeted Therapy Plus Pembrolizumab in 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: NCT03149029
Recruitment Status : Active, not recruiting
First Posted : May 11, 2017
Results First Posted : September 8, 2023
Last Update Posted : March 21, 2024
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Ryan J Sullivan, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Melanoma
Interventions Drug: Pembrolizumab
Drug: Dabrafenib
Drug: Trametinib
Enrollment 16
Recruitment Details  
Pre-assignment Details Only 5/14 BRAFV600 mutant patients had clinical benefit and the threshold for opening the BRAFV600 wild type cohort was 9/14 patients. Therefore, no BRAFV600 wild type patients were enrolled.
Arm/Group Title BRAFV600 Mutant BRAFV600 Wild Type
Hide Arm/Group Description
  • Pembrolizumab administered intravenously every three weeks
  • Dabrafenib taken every twelve hours orally
  • Trametinib taken every twelve hours orally

Pembrolizumab: Pembrolizumab is a type of antibody that inhibits the cancer cell growth

Dabrafenib: Dabrafenib is also a cell inhibitor and works by stopping the cancer cell from duplicating

Trametinib: Trametinib is a cell inhibitor that binds to the cancer cells to inhibit the cancer cells' signals to decrease cell growth
  • Pembrolizumab administered intravenously every three weeks
  • Trametinib taken every twelve hours orally

Pembrolizumab: Pembrolizumab is a type of antibody that inhibits the cancer cell growth

Trametinib: Trametinib is a cell inhibitor that binds to the cancer cells to inhibit the cancer cells' signals to decrease cell growth
Period Title: Overall Study
Started 16 0
Completed 14 0
Not Completed 2 0
Reason Not Completed
Adverse Event             2             0
Arm/Group Title BRAFV600 Mutant BRAFV600 Wild Type Total
Hide Arm/Group Description
  • Pembrolizumab administered intravenously every three weeks
  • Dabrafenib taken every twelve hours orally
  • Trametinib taken every twelve hours orally

Pembrolizumab: Pembrolizumab is a type of antibody that inhibits the cancer cell growth

Dabrafenib: Dabrafenib is also a cell inhibitor and works by stopping the cancer cell from duplicating

Trametinib: Trametinib is a cell inhibitor that binds to the cancer cells to inhibit the cancer cells' signals to decrease cell growth
  • Pembrolizumab administered intravenously every three weeks
  • Trametinib taken every twelve hours orally

Pembrolizumab: Pembrolizumab is a type of antibody that inhibits the cancer cell growth

Trametinib: Trametinib is a cell inhibitor that binds to the cancer cells to inhibit the cancer cells' signals to decrease cell growth

 Total of all reporting groups
Overall Number of Baseline Participants 14 0 14
Hide Baseline Analysis Population Description
No BRAFV600 wild type subjects were enrolled due to insufficient funding.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 0 participants 14 participants
58.6  (12.4) 58.6  (12.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 0 participants 14 participants
Female
3
  21.4%
3
  21.4%
Male
11
  78.6%
11
  78.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 0 participants 14 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
White
14
 100.0%
14
 100.0%
More than one race
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1.Primary Outcome
Title The Rate of Clinical Benefit
Hide Description

The rate of clinical benefit is defined as the percentage of patients with stable disease, partial response, or complete response 6 months after the start of treatment per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) while remaining off MAPK-targeted therapy after induction. Response to treatment was assessed using radiographic imaging.

A partial response (PR) is defined as a decrease in the sum of the longest diameters (SLD) of target lesions greater than or equal to 30%, no new lesions, and no progression of non-target lesions.

A complete response (CR) is defined as the disappearance of all lesions and pathologic lymph nodes.

Stable disease is defined as no PR, CR, or progressive disease (PD). PD is defined as an increase in the SLD of target lesions greater than or equal to 20% in comparison with the smallest SLD on study, progression of non-target lesions, or the appearance of new lesions.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
No BRAFV600 wild type patients were enrolled.
Arm/Group Title BRAFV600 Mutant BRAFV600 Wild Type
Hide Arm/Group Description:
  • Pembrolizumab administered intravenously every three weeks
  • Dabrafenib taken every twelve hours orally
  • Trametinib taken every twelve hours orally

Pembrolizumab: Pembrolizumab is a type of antibody that inhibits the cancer cell growth

Dabrafenib: Dabrafenib is also a cell inhibitor and works by stopping the cancer cell from duplicating

Trametinib: Trametinib is a cell inhibitor that binds to the cancer cells to inhibit the cancer cells' signals to decrease cell growth
  • Pembrolizumab administered intravenously every three weeks
  • Trametinib taken every twelve hours orally

Pembrolizumab: Pembrolizumab is a type of antibody that inhibits the cancer cell growth

Trametinib: Trametinib is a cell inhibitor that binds to the cancer cells to inhibit the cancer cells' signals to decrease cell growth
Overall Number of Participants Analyzed 14 0
Measure Type: Count of Participants
Unit of Measure: Participants
5
  35.7%
2.Secondary Outcome
Title Overall Survival at 1 Year
Hide Description Overall survival is the time between the first dose of targeted therapy and death from any cause. Overall survival at 1 year is defined as the proportion of participants who were alive one year after starting treatment. For patients who were lost to follow-up or who had no documentation of death at the time of final analysis, follow-up was censored at the date of last assessment of vital status. Confidence intervals are based on log (-log(endpoint)) methodology.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
No BRAFV600 wild type subjects were enrolled. 2 participants of the original 16 were excluded from the analysis because they didn't receive pembrolizumab, and survival data was not available for 2 additional subjects.
Arm/Group Title BRAFV600 Mutant BRAFV600 Wild Type
Hide Arm/Group Description:
  • Pembrolizumab administered intravenously every three weeks
  • Dabrafenib taken every twelve hours orally
  • Trametinib taken every twelve hours orally

Pembrolizumab: Pembrolizumab is a type of antibody that inhibits the cancer cell growth

Dabrafenib: Dabrafenib is also a cell inhibitor and works by stopping the cancer cell from duplicating

Trametinib: Trametinib is a cell inhibitor that binds to the cancer cells to inhibit the cancer cells' signals to decrease cell growth
  • Pembrolizumab administered intravenously every three weeks
  • Trametinib taken every twelve hours orally

Pembrolizumab: Pembrolizumab is a type of antibody that inhibits the cancer cell growth

Trametinib: Trametinib is a cell inhibitor that binds to the cancer cells to inhibit the cancer cells' signals to decrease cell growth
Overall Number of Participants Analyzed 12 0
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: proportion of participants
0.656
(0.233 to 0.885)
3.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS is defined as the time from the start of study treatment until progressive disease (PD) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) criteria or death due to any cause. Participants alive without disease progression are censored at the the date of last disease evaluation. PD is defined as an increase in the SLD of target lesions greater than or equal to 20% in comparison with the smallest SLD on study, progression of non-target lesions, or the appearance of new lesions. Confidence intervals are based on log (-log(endpoint)) methodology.
Time Frame Up to 62 months
Hide Outcome Measure Data
Hide Analysis Population Description
No BRAFV600 wild type subjects were enrolled. 2 of the original 16 subjects were excluded from the analysis since they didn't receive pembrolizumab, and progression data was not available for one additional subject.
Arm/Group Title BRAFV600 Mutant BRAFV600 Wild Type
Hide Arm/Group Description:
  • Pembrolizumab administered intravenously every three weeks
  • Dabrafenib taken every twelve hours orally
  • Trametinib taken every twelve hours orally

Pembrolizumab: Pembrolizumab is a type of antibody that inhibits the cancer cell growth

Dabrafenib: Dabrafenib is also a cell inhibitor and works by stopping the cancer cell from duplicating

Trametinib: Trametinib is a cell inhibitor that binds to the cancer cells to inhibit the cancer cells' signals to decrease cell growth
  • Pembrolizumab administered intravenously every three weeks
  • Trametinib taken every twelve hours orally

Pembrolizumab: Pembrolizumab is a type of antibody that inhibits the cancer cell growth

Trametinib: Trametinib is a cell inhibitor that binds to the cancer cells to inhibit the cancer cells' signals to decrease cell growth
Overall Number of Participants Analyzed 13 0
Median (90% Confidence Interval)
Unit of Measure: months
4.73
(3.48 to 6.8)
Time Frame AEs collected up to 2 years, 5 months (from first dose of study treatment until 90 days after the last dose of study treatment.) All cause mortality was assessed up to 62 months.
Adverse Event Reporting Description In addition to the clinicaltrials.gov definitions, (1) Pyrexia accompanied by hypotension, dehydration, renal insufficiency and/or severe (grade 3+) rigors/chills in the absence of an obvious infectious cause, (2) Occurrence of Cutaneous squamous cell carcinoma (SCC), and (3) Central serous retinopathy (CSR) and Retinal Vein Occlusion (RVO) are also considered serious adverse events.
 
Arm/Group Title BRAFV600 Mutant (Dabrafenib, Trametinib, and Pembrolizumab) BRAFV600 Wild Type BRAFV600 Mutant (Dabrafenib and Trametinib ONLY)
Hide Arm/Group Description
  • Pembrolizumab administered intravenously every three weeks
  • Dabrafenib taken every twelve hours orally
  • Trametinib taken every twelve hours orally

Pembrolizumab: Pembrolizumab is a type of antibody that inhibits the cancer cell growth

Dabrafenib: Dabrafenib is also a cell inhibitor and works by stopping the cancer cell from duplicating

Trametinib: Trametinib is a cell inhibitor that binds to the cancer cells to inhibit the cancer cells' signals to decrease cell growth
  • Pembrolizumab administered intravenously every three weeks
  • Trametinib taken every twelve hours orally

Pembrolizumab: Pembrolizumab is a type of antibody that inhibits the cancer cell growth

Trametinib: Trametinib is a cell inhibitor that binds to the cancer cells to inhibit the cancer cells' signals to decrease cell growth
  • Dabrafenib taken every twelve hours orally
  • Trametinib taken every twelve hours orally

Subjects were enrolled to the BRAFV600 mutant arm but did NOT receive pembrolizumab due to toxicity from Dabrafenib/Trametinib and discontinued from the study early. They were therefore excluded from analysis for the primary and secondary outcome measures, but adverse event data is available for these patients.

Dabrafenib: Dabrafenib is also a cell inhibitor and works by stopping the cancer cell from duplicating

Trametinib: Trametinib is a cell inhibitor that binds to the cancer cells to inhibit the cancer cells' signals to decrease cell growth
All-Cause Mortality
BRAFV600 Mutant (Dabrafenib, Trametinib, and Pembrolizumab) BRAFV600 Wild Type BRAFV600 Mutant (Dabrafenib and Trametinib ONLY)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/14 (14.29%)      0/0      0/2 (0.00%)    
Hide Serious Adverse Events
BRAFV600 Mutant (Dabrafenib, Trametinib, and Pembrolizumab) BRAFV600 Wild Type BRAFV600 Mutant (Dabrafenib and Trametinib ONLY)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/14 (42.86%)      0/0      0/2 (0.00%)    
Gastrointestinal disorders       
Abdominal Pain † 1  1/14 (7.14%)  1 /0  /2 
Diarrhea † 1  1/14 (7.14%)  2 /0  /2 
General disorders       
Fever † 1  2/14 (14.29%)  4 /0  /2 
Fatigue † 1  1/14 (7.14%)  1 /0  /2 
Infections and infestations       
Sepsis † 1  1/14 (7.14%)  1 /0  /2 
Investigations       
Aspartate Aminotransferase Increased † 1  1/14 (7.14%)  1 /0  /2 
Alanine Aminotransferase Increased † 1  1/14 (7.14%)  1 /0  /2 
Nervous system disorders       
Syncope † 1  1/14 (7.14%)  1 /0  /2 
Headache † 1  1/14 (7.14%)  1 /0  /2 
Dizziness † 1  1/14 (7.14%)  1 /0  /2 
Renal and urinary disorders       
Acute kidney injury † 1  1/14 (7.14%)  1 /0  /2 
Chronic Kidney Disease † 1  1/14 (7.14%)  1 /0  /2 
Skin and subcutaneous tissue disorders       
Rash macro-papular † 1  1/14 (7.14%)  1 /0  /2 
Vascular disorders       
Hypotension † 1  1/14 (7.14%)  1 /0  /2 
1
Term from vocabulary, CTCAE (4.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
BRAFV600 Mutant (Dabrafenib, Trametinib, and Pembrolizumab) BRAFV600 Wild Type BRAFV600 Mutant (Dabrafenib and Trametinib ONLY)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/14 (92.86%)      0/0      2/2 (100.00%)    
Blood and lymphatic system disorders       
Anemia † 1  5/14 (35.71%)  9 /0  0/2 (0.00%) 
Elevated Crp † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Lymphadenopathy † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Varicose veins † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Cardiac disorders       
Chest pain - cardiac † 1  1/14 (7.14%)  2 /0  0/2 (0.00%) 
Palpitations † 1  2/14 (14.29%)  2 /0  0/2 (0.00%)  0
Sinus tachycardia † 1  3/14 (21.43%)  3 /0  0/2 (0.00%)  0
Tachycardia † 1  2/14 (14.29%)  2 /0  0/2 (0.00%)  0
Ear and labyrinth disorders       
Ear pain † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Ear pressure † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Eustachian Tube Dysfunction † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
High Frequency Sensorineural Hearing Loss † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Endocrine disorders       
Adrenal Insufficiency † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Hypophysitis † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Eye disorders       
Acute Posterior Vitreous Detachment † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Blurred vision † 1  2/14 (14.29%)  5 /0  0/2 (0.00%) 
Cotton wool spots † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Eye pain † 1  2/14 (14.29%)  2 /0  0/2 (0.00%)  0
Lamella Macular Hole † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Ocular migraine † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Optic nerve disorder † 1  1/14 (7.14%)  2 /0  0/2 (0.00%)  0
Papilledema † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Posterior Capsule Opacification † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Uveitis † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Visual disturbance † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Gastrointestinal disorders       
Abdominal Pain † 1  6/14 (42.86%)  12 /0  1/2 (50.00%)  1
Bloating † 1  3/14 (21.43%)  3 /0  0/2 (0.00%) 
Colitis † 1  2/14 (14.29%)  2 /0  0/2 (0.00%) 
Constipation † 1  2/14 (14.29%)  2 /0  1/2 (50.00%)  1
Diarrhea † 1  9/14 (64.29%)  24 /0  1/2 (50.00%)  1
Diverticulosis † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Dry mouth † 1  2/14 (14.29%)  2 /0  0/2 (0.00%)  0
Dyspepsia † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Dysphagia † 1  1/14 (7.14%)  2 /0  0/2 (0.00%)  0
Esophageal Candidiasis † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Esophagitis † 1  1/14 (7.14%)  2 /0  0/2 (0.00%)  0
Fecal incontinence † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Flatulence † 1  2/14 (14.29%)  3 /0  1/2 (50.00%)  1
Gastritis † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Gastroesophageal reflux disease † 1  2/14 (14.29%)  4 /0  0/2 (0.00%)  0
Gastrointestinal Disorders - Other: Oral Lesions † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Hemorrhoidal hemorrhage † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Lip pain † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Nausea † 1  9/14 (64.29%)  15 /0  2/2 (100.00%)  2
Toothache † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Vomiting † 1  5/14 (35.71%)  11 /0  0/2 (0.00%)  0
General disorders       
Chills † 1  11/14 (78.57%)  30 /0  1/2 (50.00%)  2
Diaphoresis † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Edema limbs † 1  3/14 (21.43%)  9 /0  0/2 (0.00%)  0
Facial Pain † 1  1/14 (7.14%)  2 /0  0/2 (0.00%)  0
Fatigue † 1  11/14 (78.57%)  21 /0  1/2 (50.00%)  2
Fever † 1  11/14 (78.57%)  40 /0  1/2 (50.00%)  3
Flu like symptoms † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Gait disturbance † 1  2/14 (14.29%)  2 /0  0/2 (0.00%)  0
Irritability † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Localized edema † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Malaise † 1  5/14 (35.71%)  5 /0  0/2 (0.00%)  0
Pain † 1  3/14 (21.43%)  3 /0  0/2 (0.00%)  0
Tenderness at site of biopsy † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Hepatobiliary disorders       
Bile duct stenosis † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Bladder Trabeculation † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Cholangitis † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Transaminitis † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Infections and infestations       
Cold sore † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Hepatitis viral † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Sinusitis † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Skin infection † 1  1/14 (7.14%)  3 /0  0/2 (0.00%)  0
Upper respiratory infection † 1  3/14 (21.43%)  3 /0  0/2 (0.00%)  0
Urinary tract infection † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Wound infection † 1  1/14 (7.14%)  2 /0  0/2 (0.00%)  0
Injury, poisoning and procedural complications       
Bruising † 1  3/14 (21.43%)  4 /0  1/2 (50.00%)  1
Cat Bite † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Fall † 1  2/14 (14.29%)  2 /0  0/2 (0.00%)  0
Fracture † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Seroma † 1  2/14 (14.29%)  4 /0  0/2 (0.00%)  0
Investigations       
Activated partial thromboplastin time prolonged † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Alanine aminotransferase increased † 1  3/14 (21.43%)  10 /0  1/2 (50.00%)  1
Alkaline phosphatase increased † 1  4/14 (28.57%)  11 /0  0/2 (0.00%) 
Aspartate aminotransferase increased † 1  4/14 (28.57%)  13 /0  1/2 (50.00%)  1
Blood bilirubin increased † 1  1/14 (7.14%)  2 /0  0/2 (0.00%) 
Cholesterol high † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Elevated Lfts † 1  0/14 (0.00%)  0 /0  1/2 (50.00%)  2
GGT increased † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Lymphocyte count decreased † 1  2/14 (14.29%)  2 /0  0/2 (0.00%)  0
Neutrophil count decreased † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Platelet count decreased † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Weight loss † 1  5/14 (35.71%)  8 /0  1/2 (50.00%)  1
White blood cell decreased † 1  4/14 (28.57%)  7 /0  0/2 (0.00%)  0
Metabolism and nutrition disorders       
Anorexia † 1  10/14 (71.43%)  16 /0  1/2 (50.00%)  1
Dehydration † 1  6/14 (42.86%)  9 /0  0/2 (0.00%) 
Hyperglycemia † 1  3/14 (21.43%)  7 /0  0/2 (0.00%)  0
Hyperkalemia † 1  2/14 (14.29%)  5 /0  0/2 (0.00%)  0
Hypoalbuminemia † 1  1/14 (7.14%)  3 /0  0/2 (0.00%)  0
Hypocalcemia † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Hypokalemia † 1  1/14 (7.14%)  2 /0  0/2 (0.00%)  0
Hyponatremia † 1  6/14 (42.86%)  13 /0  0/2 (0.00%)  0
Hypophosphatemia † 1  6/14 (42.86%)  12 /0  0/2 (0.00%)  0
Polydipsia † 1  1/14 (7.14%)  2 /0  0/2 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  4/14 (28.57%)  8 /0  0/2 (0.00%) 
Back pain † 1  3/14 (21.43%)  3 /0  0/2 (0.00%) 
Chest wall pain † 1  2/14 (14.29%)  2 /0  0/2 (0.00%) 
Flank pain † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Generalized muscle weakness † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Muscle cramps † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Muscle weakness lower limb † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Musculoskeletal And Connective Tissue Disorders-Other: Gout † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Myalgia † 1  4/14 (28.57%)  4 /0  0/2 (0.00%)  0
Neck pain † 1  2/14 (14.29%)  2 /0  0/2 (0.00%)  0
Pain in extremity † 1  2/14 (14.29%)  2 /0  0/2 (0.00%)  0
Tenderness left elbow † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Adenoma in Bladder † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Adnexal Cyst † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Angioma Myolipoma † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Nabothian Cystan † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Pigmented bladder nodule † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Right Ovarian Cyst † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Tumor Pain † 1  2/14 (14.29%)  4 /0  0/2 (0.00%)  0
Nervous system disorders       
Dizziness † 1  6/14 (42.86%)  12 /0  0/2 (0.00%)  0
Dysgeusia † 1  2/14 (14.29%)  3 /0  1/2 (50.00%)  1
Headache † 1  8/14 (57.14%)  21 /0  0/2 (0.00%)  0
Intermittent Lightheadedness † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Paresthesia † 1  3/14 (21.43%)  4 /0  0/2 (0.00%)  0
Presyncope † 1  2/14 (14.29%)  3 /0  0/2 (0.00%)  0
Syncope † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Tremor † 1  2/14 (14.29%)  2 /0  0/2 (0.00%)  0
Vasovagal reaction † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Psychiatric disorders       
Anxiety † 1  2/14 (14.29%)  2 /0  0/2 (0.00%) 
Confusion † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Depression † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Insomnia † 1  5/14 (35.71%)  5 /0  0/2 (0.00%)  0
Renal and urinary disorders       
Dysuria † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Hematuria † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Nocturia † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Pressure with urination † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Renal calculi † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Urinary frequency † 1  5/14 (35.71%)  6 /0  0/2 (0.00%)  0
Urinary Incontinence † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Urinary urgency † 1  1/14 (7.14%)  3 /0  0/2 (0.00%)  0
Urine discoloration † 1  2/14 (14.29%)  2 /0  0/2 (0.00%)  0
Reproductive system and breast disorders       
Irregular menstruation † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Reproductive System And Breast Disorders-Other: Prostatic Hypertrophy † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Vaginal dryness † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Aspiration † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Bronchial thickening † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Cough † 1  6/14 (42.86%)  8 /0  1/2 (50.00%)  1
Dyspnea † 1  3/14 (21.43%)  4 /0  0/2 (0.00%)  0
Epistaxis † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Mild paraseptal emphysema † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Nasal congestion † 1  4/14 (28.57%)  5 /0  0/2 (0.00%)  0
Postnasal drip † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Productive cough † 1  1/14 (7.14%)  2 /0  0/2 (0.00%)  0
Sore throat † 1  2/14 (14.29%)  2 /0  0/2 (0.00%)  0
Voice alteration † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Wheezing † 1  2/14 (14.29%)  4 /0  0/2 (0.00%)  0
Skin and subcutaneous tissue disorders       
Acne Vulgaris † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Actinic Keratosis † 1  1/14 (7.14%)  1 /0  0/2 (0.00%) 
Dry skin † 1  2/14 (14.29%)  2 /0  0/2 (0.00%)  0
Erythema † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Erythema Nodosum † 1  2/14 (14.29%)  2 /0  0/2 (0.00%)  0
Erythematous rash † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Hyperhidrosis † 1  1/14 (7.14%)  2 /0  0/2 (0.00%)  0
Nail thinning † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Night sweats † 1  2/14 (14.29%)  2 /0  0/2 (0.00%)  0
Pain of skin † 1  1/14 (7.14%)  2 /0  0/2 (0.00%)  0
Palmar-plantar erythrodysesthesia syndrome † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Pruritis † 1  6/14 (42.86%)  8 /0  0/2 (0.00%)  0
Rash † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Rash acneiform † 1  3/14 (21.43%)  4 /0  0/2 (0.00%)  0
Rash macro-papular † 1  7/14 (50.00%)  18 /0  0/2 (0.00%)  0
Seborrheic Keratosis † 1  3/14 (21.43%)  3 /0  0/2 (0.00%)  0
Skin And Subcutaneous Tissue Disorders- Other: Vulvar Lesions † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Skin hypopigmentation † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Subcutaneous Mass † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Venous statis changes † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Vitiligo † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Xerosis † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Surgical and medical procedures       
Soreness at site of mass resection † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
Vascular disorders       
Flushing † 1  1/14 (7.14%)  3 /0  0/2 (0.00%)  0
Hot flashes † 1  4/14 (28.57%)  5 /0  0/2 (0.00%)  0
Hypertension † 1  1/14 (7.14%)  3 /0  0/2 (0.00%)  0
Hypotension † 1  4/14 (28.57%)  6 /0  0/2 (0.00%)  0
Vasculitis † 1  1/14 (7.14%)  1 /0  0/2 (0.00%)  0
1
Term from vocabulary, CTCAE (4.0)
†
Indicates events were collected by systematic assessment
Only 5/14 BRAFV600 mutant patients had clinical benefit and the threshold for opening the BRAFV600 wild type cohort was 9/14 patients. Therefore, no BRAFV600 wild type patients were enrolled.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Ryan J. Sullivan, MD
Organization: Massachusetts General Hospital Cancer Center
Phone: 617-643-3614
EMail: RSULLIVAN7@mgh.harvard.edu
Layout table for additonal information
Responsible Party: Ryan J Sullivan, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT03149029    
Other Study ID Numbers: 16-642
First Submitted: May 8, 2017
First Posted: May 11, 2017
Results First Submitted: June 8, 2023
Results First Posted: September 8, 2023
Last Update Posted: March 21, 2024