Adjuvant Dabrafenib (GSK2118436) in Patients With Surgically Resected AJCC Stage IIIC Melanoma Characterized by a BRAFV600E/K Mutation

A Phase 2 Trial of Adjuvant Dabrafenib (GSK2118436) in Patients With Surgically Resected AJCC Stage IIIC Melanoma Characterized by a BRAFV600E/K Mutation

In this study, the investigator's want to find out if dabrafenib can stop stage IIIC melanoma from coming back after surgery.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Drug: Dabrafenib

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• AJCC (2009) stage IIIC cutaneous melanoma rendered free of disease by surgical resection no greater than 90 days prior study enrollment. Patients with unknown primaries will be eligible for this trial. Patients with a history of resected stage I or II cutaneous melanoma who subsequently have their first disease recurrence meeting the criteria for stage IIIC disease will also be eligible for this trial.
• Patients must have clear margins after wide local excision. Patients with nodes that are palpable or detectable on radiologic imaging must have an adequate lymphadenectomy.
• Patients must be adequately recovered from surgery, radiation therapy, or any surgical complications prior to enrollment. In general, this means patients will be off antibiotics from wound infections and drains removed. However, if necessary, patients can be treated with a drain in place at the discretion of the PI if the 90 days window is about to expire.
• Histologic proof of melanoma reviewed and confirmed by MSKCC.
• A documented BRAFV600E or BRAFV600K mutation by genotyping or IHC [35]performed by a CLIA certified laboratory.
• Age ≥ 16 years old
• ECOG performance status = 0 or Karnofsky Performance Status equivalent
• The ability to swallow pills.
• Patients must have adequate organ and marrow function as defined below:

Absolute neutrophil count ≥1.5 K/mcL Platelets ≥ 100 K/mcL Hemoglobin ≥ 9.0 g/dL Total bilirubin ≤ 1.5 X institutional upper limit of normal (ULN)

≤ 3.0 X institutional ULN if the patient has Gilbert's Syndrome AST (SGOT) and ALT (SGPT) ≤ 2.5 X institutional ULN Creatinine ≤ 1.5 X institutional ULN or creatinine clearance (calculated or measured) > 60 ml/min

• Women with child bearing potential and men with reproductive potential must be willing to practice acceptable methods of contraception.

Exclusion Criteria:

• Patients with a history of stage III melanoma (any primary melanoma with locoregional nodal/subcutaneous disease) treated with surgical resection who subsequently have disease recurrence meeting the criteria for stage IIIC disease.
• Prior therapy with ipilimumab, other BRAF inhibitors, or MEK inhibitors.
• Concurrent adjuvant immunotherapy, chemotherapy, or radiotherapy.
• Current use of a prohibited medication while on dabrafenib
• Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs.
• A history of known glucose-6-phosphate dehydrogenase (G6PD) deficiency.
• Pregnant women and lactating women.
• A concurrent second malignancy even if it does not require active therapy. Patients with indolent B-cell malignancies will not be eligible. Prior malignancy will be allowed as long as the patient is known to be free of disease for at least 3 years.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• QTc interval > 500 msec unless a bundle branch block is also present.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dabrafenib; This is a single institution phase II trial assessing the efficacy of adjuvant dabrafenib (GSK2118436) in patients with surgically resected AJCC stage IIIC melanoma characterized by a BRAFV600E/K mutation.	Drug: Dabrafenib; Following definitive surgical resection, eligible patients will receive dabrafenib at 150 mg twice a day by mouth for 4 cycles (± 5 days). One cycle is 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Relapse Free Survival	Relapse free survival is defined as the time from surgical resection to the first recurrence or death as assessed by physical examination and radiographic evaluation. All recurrences will be confirmed by biopsy and histologic evaluation.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival is defined as the time from surgical resection to death or last follow-up.	2 years
Number of Participants With Adverse Events	Toxicity will be graded by the NCI Common Toxicity Criteria (CTC) version 4.0 with each cycle of adjuvant dabrafenib.	1 year

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Novartis; National Comprehensive Cancer Network

Publications and helpful links

Helpful Links

• Memorial Sloan-Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2012
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: September 6, 2012
• First Submitted That Met QC Criteria: September 6, 2012
• First Posted (Estimate): September 10, 2012

Study Record Updates

• Last Update Posted (Actual): May 26, 2020
• Last Update Submitted That Met QC Criteria: May 8, 2020
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: BRAFV600E/K; Dabrafenib; (GSK2118436); Resected AJCC Stage IIIC; 12-124
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dabrafenib
• Other Study ID Numbers: 12-124