NCT01701037

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

Biomarkers of Response and Resistance to Sequential B-RAF and MEK Targeted Therapy in a Pre-Surgical Model of Advanced, Operable Melanoma

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: Vanderbilt-Ingram Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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. TERTIARY OBJECTIVES: 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. OUTLINE: 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.

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

Type	Name	Description
DRUG	dabrafenib	150 mg given PO
DRUG	trametinib	2 mg given PO
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

• Start date: 2013-01-01
• Primary completion: 2015-02-01
• Completion: 2015-04-01
• First posted: 2012-10-04
• Last updated: 2017-06-23
• Results posted: 2017-06-23

Locations

1 site across 1 country: United States