Trial Outcomes & Findings for Dabrafenib Alone and in Combination With Trametinib Before Surgery in Treating Patients With Locally or Regionally Advanced Melanoma That Can Be Removed By Surgery (NCT NCT01701037)

Last Updated: 2017-06-23

Results Overview

Tumor response is defined as greater than 30% reduction from baseline in tumor volume by RECIST criteria. To determine whether a patient is responded at day 14, the patient must have the tumor volume evaluated at both baseline and day 14. The tumor response rate is calculated as the proportion of patients responded among all evaluated patients.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

day 14

Results posted on

2017-06-23

Participant Flow

This study opened to accrual at Vanderbilt-Ingram Cancer Center (VICC) in January 2013 and ran through March 2015 when it closed prematurely due to PI's departure.

Thirteen patients participated in this study, all completed the study as defined by protocol.

Participant milestones

Participant milestones
Measure	Basic Science (Dabrafenib, Trametinib) Patients receive dabrafenib PO BID on days 1-28 adding trametinib on days 15-28 followed by surgery on days 28-30. Treatment continues in the absence of unacceptable toxicity. dabrafenib: 150 mg given PO trametinib: 2 mg given PO laboratory biomarker analysis: Correlative studies
Overall Study STARTED	13
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Dabrafenib Alone and in Combination With Trametinib Before Surgery in Treating Patients With Locally or Regionally Advanced Melanoma That Can Be Removed By Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Basic Science (Dabrafenib, Trametinib) n=13 Participants Patients receive dabrafenib PO BID on days 1-28 adding trametinib on days 15-28 followed by surgery on days 28-30. Treatment continues in the absence of unacceptable toxicity. dabrafenib: 150 mg given PO trametinib: 2 mg given PO laboratory biomarker analysis: Correlative studies
Age, Customized 20-29	1 Participants n=5 Participants
Age, Customized 30-39	2 Participants n=5 Participants
Age, Customized 40-49	2 Participants n=5 Participants
Age, Customized 50-59	3 Participants n=5 Participants
Age, Customized 60-69	3 Participants n=5 Participants
Age, Customized 70-79	2 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	13 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: day 14

Outcome measures

Outcome measures
Measure	Dabrafenib and Trametinib n=12 Participants Patients receive dabrafenib PO BID on days 1-28 adding trametinib on days 15-28 followed by surgery on days 28-30. Treatment continues in the absence of unacceptable toxicity. dabrafenib: 150 mg given PO trametinib: 2 mg given PO laboratory biomarker analysis: Correlative studies
Clinical Tumor Response Rate (Response is Based on Greater Than 30% Reduction From Baseline in Tumor Volume by RECIST Criteria) at Day 14.	0.833 proportion of responders Interval 0.552 to 0.953

SECONDARY outcome

Timeframe: Day 14 and day 28

Tumor volume reduction is calculated as the tumor volume change relative to the baseline measurement (percent). Change in tumor volume reduction from day 14 to day 28 is calculated as the difference of tumor volume reduction at day 28 and day 14. The median and Inter-Quartile Range are reported.

Outcome measures

Outcome measures
Measure	Dabrafenib and Trametinib n=11 Participants Patients receive dabrafenib PO BID on days 1-28 adding trametinib on days 15-28 followed by surgery on days 28-30. Treatment continues in the absence of unacceptable toxicity. dabrafenib: 150 mg given PO trametinib: 2 mg given PO laboratory biomarker analysis: Correlative studies
Change in Tumor Volume Reduction in Participants With Intrinsic Resistance to B-RAF Targeted Therapy From Day 14 to Day 28.	18.0 percentage of reduction Interval 16.5 to 23.5

SECONDARY outcome

Timeframe: Up to 3 months

The intensity of the adverse event will be graded according to Version 4.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events (June 14, 2010): Grade 1 - Mild Grade 2 - Moderate Grade 3 - Severe or medically significant Grade 4 - Life-threatening Grade 5 - Death related to adverse event

Outcome measures

Outcome measures
Measure	Dabrafenib and Trametinib n=13 Participants Patients receive dabrafenib PO BID on days 1-28 adding trametinib on days 15-28 followed by surgery on days 28-30. Treatment continues in the absence of unacceptable toxicity. dabrafenib: 150 mg given PO trametinib: 2 mg given PO laboratory biomarker analysis: Correlative studies
Number of Patients With Worst Grade Toxicities by Grade According to National Cancer Institute (NCI) CTCAE Version 4.0 Number of patients with worst-grade toxicity 5	0 participants
Number of Patients With Worst Grade Toxicities by Grade According to National Cancer Institute (NCI) CTCAE Version 4.0 Number of patients with worst-grade toxicity 1	1 participants
Number of Patients With Worst Grade Toxicities by Grade According to National Cancer Institute (NCI) CTCAE Version 4.0 Number of patients with worst-grade toxicity 2	6 participants
Number of Patients With Worst Grade Toxicities by Grade According to National Cancer Institute (NCI) CTCAE Version 4.0 Number of patients with worst-grade toxicity 3	6 participants
Number of Patients With Worst Grade Toxicities by Grade According to National Cancer Institute (NCI) CTCAE Version 4.0 Number of patients with worst-grade toxicity 4	0 participants

SECONDARY outcome

Timeframe: Up to 3 months

Median number of pills taken

Outcome measures

Outcome measures
Measure	Dabrafenib and Trametinib n=13 Participants Patients receive dabrafenib PO BID on days 1-28 adding trametinib on days 15-28 followed by surgery on days 28-30. Treatment continues in the absence of unacceptable toxicity. dabrafenib: 150 mg given PO trametinib: 2 mg given PO laboratory biomarker analysis: Correlative studies
Investigational Agent Taken Median number of GSK1120212 taken	13 Number of pills taken Standard Deviation 1.90
Investigational Agent Taken Median number of GSK2118436 taken	54 Number of pills taken Standard Deviation 6.34

SECONDARY outcome

Timeframe: Up to 3 months

Biopsies will be assessed whether or not tissue is acquired at specified time points. Tissue is obtained through core, punch, incisional or excisional biopsy or surgical resection, based upon the clinical situation. Standard operating procedures for biopsies, sample preparation and analysis have been defined.

Outcome measures

Outcome measures
Measure	Dabrafenib and Trametinib n=13 Participants Patients receive dabrafenib PO BID on days 1-28 adding trametinib on days 15-28 followed by surgery on days 28-30. Treatment continues in the absence of unacceptable toxicity. dabrafenib: 150 mg given PO trametinib: 2 mg given PO laboratory biomarker analysis: Correlative studies
Percent of Patients Completing Second and Third (Surgical) Biopsies	92 percentage of participants

SECONDARY outcome

Timeframe: Up to 3 months

Measured by the percent of tumor necrosis on hematoxylin and eosin stains; RNA gel electrophoresis, percent of adequate tissue for immunohistochemical stains in tissue microarray and cyTOF analysis.

Outcome measures

Outcome measures
Measure	Dabrafenib and Trametinib n=13 Participants Patients receive dabrafenib PO BID on days 1-28 adding trametinib on days 15-28 followed by surgery on days 28-30. Treatment continues in the absence of unacceptable toxicity. dabrafenib: 150 mg given PO trametinib: 2 mg given PO laboratory biomarker analysis: Correlative studies
Percentage of Biopsies With Adequate Tissue for Biomarker Analysis	92 percentage of biopsies w/adequate tissue

Adverse Events

Basic Science (Dabrafenib, Trametinib)

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Basic Science (Dabrafenib, Trametinib) n=13 participants at risk Patients receive dabrafenib PO BID on days 1-28 adding trametinib on days 15-28 followed by surgery on days 28-30. Treatment continues in the absence of unacceptable toxicity. dabrafenib: 150 mg given PO trametinib: 2 mg given PO laboratory biomarker analysis: Correlative studies
Cardiac disorders Atrial fibrillation	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Nervous system disorders Stroke	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Renal and urinary disorders Kidney Injury	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.

Other adverse events

Other adverse events
Measure	Basic Science (Dabrafenib, Trametinib) n=13 participants at risk Patients receive dabrafenib PO BID on days 1-28 adding trametinib on days 15-28 followed by surgery on days 28-30. Treatment continues in the absence of unacceptable toxicity. dabrafenib: 150 mg given PO trametinib: 2 mg given PO laboratory biomarker analysis: Correlative studies
General disorders Fatigue	61.5% 8/13 • Number of events 10 • Serious adverse events and Adverse events were collected over 25 months period.
General disorders Chills	38.5% 5/13 • Number of events 7 • Serious adverse events and Adverse events were collected over 25 months period.
General disorders Fever	23.1% 3/13 • Number of events 4 • Serious adverse events and Adverse events were collected over 25 months period.
General disorders Pain	15.4% 2/13 • Number of events 2 • Serious adverse events and Adverse events were collected over 25 months period.
General disorders Edema, limbs	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
General disorders Facial pain	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Skin and subcutaneous tissue disorders Rash maculo-papular	53.8% 7/13 • Number of events 7 • Serious adverse events and Adverse events were collected over 25 months period.
Skin and subcutaneous tissue disorders Pruritus	23.1% 3/13 • Number of events 3 • Serious adverse events and Adverse events were collected over 25 months period.
Skin and subcutaneous tissue disorders Generalized skin senstivity	15.4% 2/13 • Number of events 2 • Serious adverse events and Adverse events were collected over 25 months period.
Skin and subcutaneous tissue disorders Alopecia	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Skin and subcutaneous tissue disorders Erythroderma	7.7% 1/13 • Number of events 2 • Serious adverse events and Adverse events were collected over 25 months period.
Skin and subcutaneous tissue disorders Hyperhidrosis	7.7% 1/13 • Number of events 2 • Serious adverse events and Adverse events were collected over 25 months period.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Nervous system disorders Headache	30.8% 4/13 • Number of events 4 • Serious adverse events and Adverse events were collected over 25 months period.
Nervous system disorders Dizziness	15.4% 2/13 • Number of events 2 • Serious adverse events and Adverse events were collected over 25 months period.
Nervous system disorders Dysgeusia	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Investigations Alanine aminotransferase increased	23.1% 3/13 • Number of events 3 • Serious adverse events and Adverse events were collected over 25 months period.
Investigations Lymphocyte count decreased	15.4% 2/13 • Number of events 2 • Serious adverse events and Adverse events were collected over 25 months period.
Investigations White blood cell decreased	15.4% 2/13 • Number of events 2 • Serious adverse events and Adverse events were collected over 25 months period.
Investigations Aspartate aminotransferase increased	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Investigations Cholesterol high	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Investigations Creatinine increased	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Investigations Platelet count decreased	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Investigations Other	7.7% 1/13 • Number of events 3 • Serious adverse events and Adverse events were collected over 25 months period.
Metabolism and nutrition disorders Hyperglycemia	46.2% 6/13 • Number of events 6 • Serious adverse events and Adverse events were collected over 25 months period.
Metabolism and nutrition disorders Hyponatremia	15.4% 2/13 • Number of events 2 • Serious adverse events and Adverse events were collected over 25 months period.
Metabolism and nutrition disorders Hyperkalemia	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Metabolism and nutrition disorders Hypoalbuminemia	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Gastrointestinal disorders Nausea	38.5% 5/13 • Number of events 5 • Serious adverse events and Adverse events were collected over 25 months period.
Gastrointestinal disorders Diarrhea	15.4% 2/13 • Number of events 2 • Serious adverse events and Adverse events were collected over 25 months period.
Gastrointestinal disorders Constipationi	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Gastrointestinal disorders Gastroesophageal reflux disease	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Gastrointestinal disorders Mucositis oral	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Gastrointestinal disorders vomiting	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Musculoskeletal and connective tissue disorders Arthralgia	38.5% 5/13 • Number of events 7 • Serious adverse events and Adverse events were collected over 25 months period.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Musculoskeletal and connective tissue disorders Other	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Blood and lymphatic system disorders Anemia	23.1% 3/13 • Number of events 3 • Serious adverse events and Adverse events were collected over 25 months period.
Cardiac disorders Other	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Infections and infestations Wound infection	15.4% 2/13 • Number of events 3 • Serious adverse events and Adverse events were collected over 25 months period.
Vascular disorders Hypertension	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Vascular disorders Hypotension	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Ear and labyrinth disorders Vertigo	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Injury, poisoning and procedural complications Seroma	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Other	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Psychiatric disorders Anxiety	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Renal and urinary disorders Hematuria	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Renal and urinary disorders Proteinuria	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Respiratory, thoracic and mediastinal disorders Nasal congestion	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Respiratory, thoracic and mediastinal disorders Productive cough	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.
Respiratory, thoracic and mediastinal disorders Other	7.7% 1/13 • Number of events 1 • Serious adverse events and Adverse events were collected over 25 months period.

Additional Information

Mark C. Kelley

Vanderbilt-Ingram Cancer Center

Phone: 615-936-7423

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place