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

NCT01701037 | Terminated Phase 2 Results DMC

• 2 other identifiers: VICC MEL 1263NCI-2012-01699
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

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)

Keywords

Melanoma, B-RAF, biomarkers, targeted therapy, resistance

Outcome Measures

Primary Outcomes (1)

• Clinical Tumor Response Rate (Response is Based on Greater Than 30% Reduction From Baseline in Tumor Volume by RECIST Criteria) at Day 14.

  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.

  day 14

Secondary Outcomes (5)

• Change in Tumor Volume Reduction in Participants With Intrinsic Resistance to B-RAF Targeted Therapy From Day 14 to Day 28.

  Day 14 and day 28

• Number of Patients With Worst Grade Toxicities by Grade According to National Cancer Institute (NCI) CTCAE Version 4.0

  Up to 3 months

• Investigational Agent Taken

  Up to 3 months

• Percent of Patients Completing Second and Third (Surgical) Biopsies

  Up to 3 months

• Percentage of Biopsies With Adequate Tissue for Biomarker Analysis

  Up to 3 months

Study Arms (1)

Dabrafenib and Trametinib

EXPERIMENTAL

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.

Drug: dabrafenib; Drug: trametinib; Other: laboratory biomarker analysis

Interventions

dabrafenib DRUG

150 mg given PO

Also known as: BRAF inhibitor GSK2118436, GSK2118436

Dabrafenib and Trametinib

trametinib DRUG

2 mg given PO

Also known as: GSK1120212

Dabrafenib and Trametinib

laboratory biomarker analysis OTHER

Correlative studies

Dabrafenib and Trametinib

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Patients with locally-or regionally advanced melanoma being considered for resection of the lesion(s) for local-regional control and potential cure
• Patients with limited, resectable metastatic disease (three or fewer lesions) are eligible if surgical resection is considered to be the best therapeutic option
• Patients with AJCC clinical stage IIb-IV disease at initial diagnosis, or patients with melanoma of any stage with advanced local or regional recurrence, with or without limited resectable metastatic disease, would be eligible
• B-RAF V-600 mutation positive by snapshot molecular analysis
• Individuals with B-RAF V-600 mutations other than V600E are eligible
• Measurable disease, i.e. presenting with at least one measurable lesion per Response Evaluation Criteria in Solid tumors (RECIST) 1.1
• All prior treatment related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) (Version 4.0) =\< Grade 1 at the time of enrollment
• Adequate baseline organ function defined by the criteria below:
• Absolute Neutrophil Count (ANC) \>= 1.5 X 10\^9/L
• Platelet Count \>= 60 X 10\^9/L
• Hemoglobin \>= 9 g/dl
• Creatinine =\< 2 mg/dl
• Aspartate aminotransferase (AST) =\< 100 U/L
• Alanine aminotransferase (ALT) =\< 100 U/L

You may not qualify if:

• ECOG Performance Status \> 2
• Lactating female
• Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures
• Any serious medical condition that would render the patient unable to undergo surgical resection or would limit life expectancy to less than 1 year
• Any prohibited medication
• Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment
• A known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK-2118436 (dabrafenib) or GSK-1120212 (trametinib) or excipient that contraindicates their participation
• Patients with a history of severe cardiovascular disease as defined:
• Symptomatic or uncontrolled cardiac arrhythmias
• Treatment refractory hypertension, defined as a systolic blood pressure \> 160mm Hg and/or diastolic \> 100 mmHg which cannot be controlled by antihypertensive therapy.
• Current ≥ NYHA Class II congestive heart failure
• History of myocardial infarction or unstable angina within 6 months prior to study entry.
• History of stroke or TIA within 6 months prior to study entry
• QTc ≥ 480 msec
• Cardiac valvular disease ≥ grade 2.

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• National Comprehensive Cancer Network: collaborator

Study Sites (1)

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

Related Publications (1)

• Johnson AS, Crandall H, Dahlman K, Kelley MC. Preliminary results from a prospective trial of preoperative combined BRAF and MEK-targeted therapy in advanced BRAF mutation-positive melanoma. J Am Coll Surg. 2015 Apr;220(4):581-93.e1. doi: 10.1016/j.jamcollsurg.2014.12.057. Epub 2015 Jan 30.

  PMID: 25797743 RESULT

Related Links

• Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

MeSH Terms

Conditions

Melanoma

Interventions

dabrafenib; trametinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Mark C. Kelley
• Organization: Vanderbilt-Ingram Cancer Center

mark.kelley@vanderbilt.edu

615-936-7423

Study Officials

• Mark Kelley

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Division of Surgical Oncology and Endocrine Surgery; Associate Professor of Surgery; Surgical Oncologist

Study Record Dates

• First Submitted: September 21, 2012
• First Posted: October 4, 2012
• Study Start: January 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: April 1, 2015
• Last Updated: June 23, 2017
• Results First Posted: June 23, 2017

Record last verified: 2017-06

Locations

US (1)