Dabrafenib Alone and in Combination With Trametinib Before Surgery in Treating Patients With Locally or Regionally Advanced Melanoma That Can Be Removed By Surgery
This phase II trial studies how well giving dabrafenib alone and in combination with trametinib before surgery works in treating patients with advanced melanoma that can be removed by surgery. Studying samples of tumor tissue in the laboratory from patients receiving dabrafenib and trametinib may help doctors learn more about the effects of these drugs on cells and help identify biomarkers that determine which patients will respond to these drugs best.
Stage IIB Melanoma (Locally Advanced)
Stage IIC Melanoma (Locally Advanced)
Stage IIIA Melanoma
Stage IIIB Melanoma
Stage IIIC Melanoma
Stage IV Melanoma (Limited, Resectable)
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||Biomarkers of Response and Resistance to Sequential B-RAF and MEK Targeted Therapy in a Pre-Surgical Model of Advanced, Operable Melanoma|
- Clinical tumor response, in terms of change (greater than 30% reduction in tumor volume by RECIST criteria) and association with biomarker expression [ Time Frame: Baseline and day 14 ] [ Designated as safety issue: No ]Tumor response summarized in frequency tables and incidence compared using the chi-square or Fisher's exact test. Biomarker expression summarized using minimum, 25th, 50th (median), 75th, and maximum values. Spearman (nonparametric) correlation statistic used to assess strength of association between biomarker expression and tumor volume between any two time points. Logistic regression used to assess the association between biomarker expression and patient response by RECIST criteria. 95% confidence intervals will be calculated for all point estimates.
- Change in incremental clinical tumor response (greater than 30% tumor volume reduction by RECIST criteria) in participants with intrinsic resistance to B-RAF targeted therapy [ Time Frame: Day 14 and day 28 ] [ Designated as safety issue: No ]Tumor response summarized in frequency tables and incidence compared using the chi-square or Fisher's exact test. Biomarker expression summarized using minimum, 25th, 50th (median), 75th, and maximum values. Spearman (nonparametric) correlation statistic used to assess strength of association between biomarker expression and tumor volume between any two time points. Logistic regression used to assess the association between biomarker expression and patient response by RECIST criteria. 95% confidence intervals will be calculated for all point estimates.
- Number of patients with worst grade toxicities by grade according to National Cancer Institute (NCI) CTCAE version 4.0 [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]Events will be summarized by frequency and proportion of total subjects, by system organ class and preferred term.
- Median number of the investigational agent taken per patient [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]Participants that receive all planned doses of the investigational agent. this outcome measure is captured by completion of a pill diary used by the patient to record pills taken.
- Percent of patients completing second and third (surgical) biopsies [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]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.
- Percentage of biopsies with adequate tissue for biomarker analysis [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]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.
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Experimental: 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.
150 mg given PO
Other Names:Drug: trametinib
2 mg given PO
Other Name: GSK1120212Other: laboratory biomarker analysis
I. To identify markers of intrinsic resistance to v-Raf murine sarcoma viral oncogene homolog B1 (B-RAF) targeted therapy in B-RAF mutation-positive melanoma.
I. To determine if intrinsic resistance can be reversed by mitogen activated protein kinase (MEK) targeted therapy and to identify biomarkers that correlate with this response.
II. To evaluate the feasibility of pre-surgical targeted therapy and serial tumor biopsies in patients with advanced, operable melanoma to determine if this model can be used to evaluate novel combinations of molecular targeted therapy in the future.
I. To determine if pre-surgical B-RAF and MEK targeted therapy is active and well tolerated in patients with advanced, operable melanoma. These findings may be used to support clinical trials in un-resectable, B-RAF mutation-positive melanoma.
Patients receive dabrafenib orally (PO) twice daily (BID) on days 1-28 adding trametinib on days 15-28 followed by surgery on days 28-30. Treatment continues until the day prior to surgery in the absence of unacceptable toxicity.
After completion of study treatment, patients are followed up for 3 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01701037
|Contact: VICC Clinical Trials Information Program||800-811-8480|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center||Recruiting|
|Nashville, Tennessee, United States, 37232-6838|
|Contact: VICC Clinical Trials Information Program 800-811-8480|
|Principal Investigator: Mark C. Kelley|
|Principal Investigator:||Mark Kelley||Vanderbilt-Ingram Cancer Center|