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

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01682213
• Collaborator: National Comprehensive Cancer Network (Other), Novartis (Industry)
• Enrollment: 23
• Location: 1
• Arm: 1
• Actual Duration (Months): 79.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Drug: Dabrafenib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: May 1, 2019
• Actual Study Completion Date: May 1, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Relapse Free Survival [24 months]

   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.

Secondary Outcome Measures

1. Overall Survival [2 years]

   Overall survival is defined as the time from surgical resection to death or last follow-up.

2. Number of Participants With Adverse Events [1 year]

   Toxicity will be graded by the NCI Common Toxicity Criteria (CTC) version 4.0 with each cycle of adjuvant dabrafenib.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• National Comprehensive Cancer Network
• Novartis

Investigators

• Principal Investigator: Paul Chapman, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 20, 2018

More Information

Additional Information:

• Memorial Sloan-Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT01682213
• Other Study ID Numbers: 12-124
• First Posted: Sep 10, 2012
• Last Update Posted: May 26, 2020
• Last Verified: May 1, 2019

• Keywords provided by Memorial Sloan Kettering Cancer Center: Dabrafenib; (GSK2118436); BRAFV600E/K; Resected AJCC Stage IIIC; 12-124
• Additional relevant MeSH terms: Melanoma; Dabrafenib

Study Results

Participant Flow

Arm/Group Title	Dabrafenib
Arm/Group Description	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. 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.
Period Title: Overall Study
STARTED	23
COMPLETED	21
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Dabrafenib
Arm/Group Description	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. 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.
Overall Participants	23
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54
Sex: Female, Male (Count of Participants)
Female	8 34.8%
Male	15 65.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 4.3%
Not Hispanic or Latino	22 95.7%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 4.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	21 91.3%
More than one race	0 0%
Unknown or Not Reported	1 4.3%
Region of Enrollment (Count of Participants)
United States	23 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Relapse Free Survival
Description	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.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

2 participants withdrew consent 1 week after signing consent

Arm/Group Title	Dabrafenib
Arm/Group Description	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. 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.
Measure Participants	21
Number [percentage of participants]	28.6 124.3%

2. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the time from surgical resection to death or last follow-up.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

2 participants withdrew consent 1 week after signing consent

Arm/Group Title	Dabrafenib
Arm/Group Description	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. 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.
Measure Participants	21
Number (95% Confidence Interval) [percentage of participants]	78 339.1%

3. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Toxicity will be graded by the NCI Common Toxicity Criteria (CTC) version 4.0 with each cycle of adjuvant dabrafenib.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dabrafenib
Arm/Group Description	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.
Measure Participants	23
Count of Participants [Participants]	23 100%

Adverse Events

Time Frame	1 year
Arm/Group Title	Dabrafenib
Arm/Group Description	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.
All Cause Mortality
	Dabrafenib
	Affected / at Risk (%)	# Events
Total	8/23 (34.8%)
Serious Adverse Events
	Dabrafenib
	Affected / at Risk (%)	# Events
Total	5/23 (21.7%)
Blood and lymphatic system disorders
Anemia	1/23 (4.3%)
General disorders
Chills	1/23 (4.3%)
Fever	2/23 (8.7%)
Investigations
Platelet count decreased	1/23 (4.3%)
White blood cell decreased	1/23 (4.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms ben/mal/unk (inccyst/polyp) Other, spec	3/23 (13%)
Nervous system disorders
Seizure	1/23 (4.3%)
Respiratory, thoracic and mediastinal disorders
Cough	1/23 (4.3%)
Other (Not Including Serious) Adverse Events
	Dabrafenib
	Affected / at Risk (%)	# Events
Total	23/23 (100%)
Blood and lymphatic system disorders
Anemia	4/23 (17.4%)
Eye disorders
Photophobia	1/23 (4.3%)
Blurred vision	2/23 (8.7%)
Gastrointestinal disorders
Diarrhea	4/23 (17.4%)
Nausea/Vomiting	4/23 (17.4%)
Dyspepsia	1/23 (4.3%)
General disorders
Fatigue	13/23 (56.5%)
Pyrexia	7/23 (30.4%)
Chills	4/23 (17.4%)
Investigations
Leukopenia	5/23 (21.7%)
Transaminitis	1/23 (4.3%)
Metabolism and nutrition disorders
Anorexia	2/23 (8.7%)
Hypophosphatemia	4/23 (17.4%)
Musculoskeletal and connective tissue disorders
Myalgia	8/23 (34.8%)
Nervous system disorders
Abducens nerve disorder	1/23 (4.3%)
Syncope	1/23 (4.3%)
Neuropathy	2/23 (8.7%)
Headache	8/23 (34.8%)
Dysgeusia	1/23 (4.3%)
Psychiatric disorders
Insomnia	1/23 (4.3%)
Respiratory, thoracic and mediastinal disorders
Sore throat	1/23 (4.3%)
Skin and subcutaneous tissue disorders
Rash	18/23 (78.3%)
Pruritus	1/23 (4.3%)
Dry Skin	2/23 (8.7%)
Hand-foot syndrome	7/23 (30.4%)
Photosensitivity	1/23 (4.3%)
Alopecia	5/23 (21.7%)
New primary melanoma	1/23 (4.3%)
Vascular disorders
Flushing	3/23 (13%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.