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

Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01682213
• Other study ID #: 12-124
• Status: Completed
• Phase: Phase 2
• Start date: September 2012
• Est. completion date: May 2019

Study information

• Verified date: May 2019
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: May 2019
• Est. primary completion date: May 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Melanoma

Intervention

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.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Comprehensive Cancer Network, Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival	Overall survival is defined as the time from surgical resection to death or last follow-up.	2 years
Secondary	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

External Links

•   Memorial Sloan-Kettering Cancer Center