Melanoma
Conditions
Keywords
Dabrafenib, (GSK2118436), BRAFV600E/K, Resected AJCC Stage IIIC, 12-124
Brief summary
In this study, the investigator's want to find out if dabrafenib can stop stage IIIC melanoma from coming back after surgery.
Interventions
DRUGDabrafenib
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.
Sponsors
National Comprehensive Cancer Network
Novartis
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 2 years | Overall survival is defined as the time from surgical resection to death or last follow-up. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Dabrafenib |
|---|---|
| Age, Continuous | 54 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Region of Enrollment United States | 23 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 23 |
| other Total, other adverse events | 23 / 23 |
| serious Total, serious adverse events | 5 / 23 |
Outcome results
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.
Time frame: 24 months
Population: 2 participants withdrew consent 1 week after signing consent
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabrafenib | Percentage of Participants With Relapse Free Survival | 28.6 percentage of participants |
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.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dabrafenib | Number of Participants With Adverse Events | 23 Participants |
Secondary
Overall Survival
Overall survival is defined as the time from surgical resection to death or last follow-up.
Time frame: 2 years
Population: 2 participants withdrew consent 1 week after signing consent
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabrafenib | Overall Survival | 78 percentage of participants |