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

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ClinicalTrials.gov Identifier: NCT01701037
Recruitment Status : Terminated (PI leaving VICC, low future accrual predicted, continued funding improbable,)
First Posted : October 4, 2012
Results First Posted : June 23, 2017
Last Update Posted : June 23, 2017
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Mark Kelley, MD, Vanderbilt-Ingram Cancer Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Conditions Recurrent Melanoma
Stage IIB Melanoma (Locally Advanced)
Stage IIC Melanoma (Locally Advanced)
Stage IIIA Melanoma
Stage IIIB Melanoma
Stage IIIC Melanoma
Stage IV Melanoma (Limited, Resectable)
Interventions Drug: dabrafenib
Drug: trametinib
Other: laboratory biomarker analysis
Enrollment 13
Recruitment Details 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.
Pre-assignment Details Thirteen patients participated in this study, all completed the study as defined by protocol.
Arm/Group Title Basic Science (Dabrafenib, Trametinib)
Hide Arm/Group Description

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

Period Title: Overall Study
Started 13
Completed 13
Not Completed 0
Arm/Group Title Basic Science (Dabrafenib, Trametinib)
Hide Arm/Group Description

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 Number of Baseline Participants 13
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
20-29
1
   7.7%
30-39
2
  15.4%
40-49
2
  15.4%
50-59
3
  23.1%
60-69
3
  23.1%
70-79
2
  15.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
Female
7
  53.8%
Male
6
  46.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
13
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
13
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 13 participants
13
 100.0%
1.Primary Outcome
Title Clinical Tumor Response Rate (Response is Based on Greater Than 30% Reduction From Baseline in Tumor Volume by RECIST Criteria) at Day 14.
Hide Description 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.
Time Frame day 14
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dabrafenib and Trametinib
Hide Arm/Group Description:

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 Number of Participants Analyzed 12
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of responders
0.833
(0.552 to 0.953)
2.Secondary Outcome
Title Change in Tumor Volume Reduction in Participants With Intrinsic Resistance to B-RAF Targeted Therapy From Day 14 to Day 28.
Hide Description 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.
Time Frame Day 14 and day 28
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dabrafenib and Trametinib
Hide Arm/Group Description:

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 Number of Participants Analyzed 11
Median (Inter-Quartile Range)
Unit of Measure: percentage of reduction
18.0
(16.5 to 23.5)
3.Secondary Outcome
Title Number of Patients With Worst Grade Toxicities by Grade According to National Cancer Institute (NCI) CTCAE Version 4.0
Hide Description

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

Time Frame Up to 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dabrafenib and Trametinib
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 13
Measure Type: Number
Unit of Measure: participants
Number of patients with worst-grade toxicity 1 1
Number of patients with worst-grade toxicity 2 6
Number of patients with worst-grade toxicity 3 6
Number of patients with worst-grade toxicity 4 0
Number of patients with worst-grade toxicity 5 0
4.Secondary Outcome
Title Investigational Agent Taken
Hide Description Median number of pills taken
Time Frame Up to 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dabrafenib and Trametinib
Hide Arm/Group Description:

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 Number of Participants Analyzed 13
Median (Standard Deviation)
Unit of Measure: Number of pills taken
Median number of GSK1120212 taken 13  (1.90)
Median number of GSK2118436 taken 54  (6.34)
5.Secondary Outcome
Title Percent of Patients Completing Second and Third (Surgical) Biopsies
Hide Description 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.
Time Frame Up to 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dabrafenib and Trametinib
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 13
Measure Type: Number
Unit of Measure: percentage of participants
92
6.Secondary Outcome
Title Percentage of Biopsies With Adequate Tissue for Biomarker Analysis
Hide Description 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.
Time Frame Up to 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dabrafenib and Trametinib
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 13
Measure Type: Number
Unit of Measure: percentage of biopsies w/adequate tissue
92
Time Frame Serious adverse events and Adverse events were collected over 25 months period.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Basic Science (Dabrafenib, Trametinib)
Hide Arm/Group Description

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

All-Cause Mortality
Basic Science (Dabrafenib, Trametinib)
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Basic Science (Dabrafenib, Trametinib)
Affected / at Risk (%) # Events
Total   1/13 (7.69%)    
Cardiac disorders   
Atrial fibrillation  1/13 (7.69%)  1
Nervous system disorders   
Stroke  1/13 (7.69%)  1
Renal and urinary disorders   
Kidney Injury  1/13 (7.69%)  1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Basic Science (Dabrafenib, Trametinib)
Affected / at Risk (%) # Events
Total   13/13 (100.00%)    
Blood and lymphatic system disorders   
Anemia  3/13 (23.08%)  3
Cardiac disorders   
Other  1/13 (7.69%)  1
Ear and labyrinth disorders   
Vertigo  1/13 (7.69%)  1
Gastrointestinal disorders   
Nausea  5/13 (38.46%)  5
Diarrhea  2/13 (15.38%)  2
Constipationi  1/13 (7.69%)  1
Gastroesophageal reflux disease  1/13 (7.69%)  1
Mucositis oral  1/13 (7.69%)  1
vomiting  1/13 (7.69%)  1
General disorders   
Fatigue  8/13 (61.54%)  10
Chills  5/13 (38.46%)  7
Fever  3/13 (23.08%)  4
Pain  2/13 (15.38%)  2
Edema, limbs  1/13 (7.69%)  1
Facial pain  1/13 (7.69%)  1
Infections and infestations   
Wound infection  2/13 (15.38%)  3
Injury, poisoning and procedural complications   
Seroma  1/13 (7.69%)  1
Investigations   
Alanine aminotransferase increased  3/13 (23.08%)  3
Lymphocyte count decreased  2/13 (15.38%)  2
White blood cell decreased  2/13 (15.38%)  2
Aspartate aminotransferase increased  1/13 (7.69%)  1
Cholesterol high  1/13 (7.69%)  1
Creatinine increased  1/13 (7.69%)  1
Platelet count decreased  1/13 (7.69%)  1
Other  1/13 (7.69%)  3
Metabolism and nutrition disorders   
Hyperglycemia  6/13 (46.15%)  6
Hyponatremia  2/13 (15.38%)  2
Hyperkalemia  1/13 (7.69%)  1
Hypoalbuminemia  1/13 (7.69%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia  5/13 (38.46%)  7
Generalized muscle weakness  1/13 (7.69%)  1
Other  1/13 (7.69%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Other  1/13 (7.69%)  1
Nervous system disorders   
Headache  4/13 (30.77%)  4
Dizziness  2/13 (15.38%)  2
Dysgeusia  1/13 (7.69%)  1
Psychiatric disorders   
Anxiety  1/13 (7.69%)  1
Renal and urinary disorders   
Hematuria  1/13 (7.69%)  1
Proteinuria  1/13 (7.69%)  1
Respiratory, thoracic and mediastinal disorders   
Nasal congestion  1/13 (7.69%)  1
Productive cough  1/13 (7.69%)  1
Other  1/13 (7.69%)  1
Skin and subcutaneous tissue disorders   
Rash maculo-papular  7/13 (53.85%)  7
Pruritus  3/13 (23.08%)  3
Generalized skin senstivity  2/13 (15.38%)  2
Alopecia  1/13 (7.69%)  1
Erythroderma  1/13 (7.69%)  2
Hyperhidrosis  1/13 (7.69%)  2
Palmar-plantar erythrodysesthesia syndrome  1/13 (7.69%)  1
Vascular disorders   
Hypertension  1/13 (7.69%)  1
Hypotension  1/13 (7.69%)  1
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: Mark C. Kelley
Organization: Vanderbilt-Ingram Cancer Center
Phone: 615-936-7423
EMail: mark.kelley@vanderbilt.edu
Layout table for additonal information
Responsible Party: Mark Kelley, MD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT01701037     History of Changes
Other Study ID Numbers: VICC MEL 1263
NCI-2012-01699 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Submitted: September 21, 2012
First Posted: October 4, 2012
Results First Submitted: March 10, 2017
Results First Posted: June 23, 2017
Last Update Posted: June 23, 2017