A Phase II Trial of Dasatinib in Patients With Unresectable Locally Advanced or Stage IV Mucosal, Acral and Vulvovaginal Melanomas
Trial status: Open for Enrollment
Why is this study being done?
- To estimate the objective tumor response rate in patients with KIT-positive, unresectable, locally advanced or metastatic acral or mucosal melanoma treated with dasatinib monotherapy.
- To estimate the response duration in patients treated with this drug.
- To estimate the progression-free survival of patients treated with this drug.
- To evaluate the safety profile of this drug in these patients.
- To evaluate the PDGFR expression and activation of Src family kinases in tumor samples and correlate these parameters with response to treatment.
OUTLINE: This is a multicenter study.
Patients receive oral dasatinib twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Tissue samples may be collected from some patients for correlative studies.
After completion of study therapy, patients are followed up periodically for up to 5 years.
Who is eligible to participate?
- Histologically or cytologically confirmed melanoma of 1 of the following subtypes:
- Acral melanoma (defined as occurring on the palms, soles, or subungual sites)
- Melanoma arising from the vagina and/or vulva
- Melanoma arising on other mucosal surface (not vagina or vulva)
- Unresectable locally advanced or metastatic disease
- c-KIT mutation identified by polymerase chain reaction (PCR) and sequencing meeting 1 of the following criteria:
- At least 1 mutation in exon 9, 11, 13, 17, or 18
- At least 1 mutation in an exon not listed above
- Metastatic tumor blocks are required for the evaluation of KIT mutations or amplifications
- Measurable disease, defined as at least one measurable lesion by RECIST criteria
- Prior radiotherapy to a measurable lesion allowed provided there is radiographic evidence of progression of that lesion
- No ocular melanoma
- Baseline bone scan required for patients with known bone metastases, elevated alkaline phosphatase, or symptoms raising suspicion of bone metastases
- History or clinical evidence of brain metastasis allowed provided the following criteria are met:
- Completed radiotherapy or surgical treatment of brain lesions AND there is no evidence of CNS progression for ≥ 8 weeks
- Must not require corticosteroids for treatment of cerebral edema from brain metastases
- ECOG performance status 0-1
- WBC ≥ 3,000/mm³
- Absolute granulocyte count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Creatinine ≤ 2.0 times upper limit of normal (ULN) OR creatinine clearance ≥ 40 mL/min
- Total bilirubin ≤ 1.5 times ULN (< 3.0 times ULN in the presence of Gilbert disease)
- AST and ALT ≤ 2.5 times ULN (≤ 5.0 times ULN in the presence of liver metastases)
- Serum potassium and magnesium normal (repletion allowed)
- Total serum calcium or ionized calcium normal
- INR ≤ 1.5 and PTT normal
- Therapeutic anticoagulation with warfarin allowed provided INR ≤ 1.5 or PTT normal prior to initiating anticoagulation therapy
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No evidence of bleeding diathesis
- No other malignancies except basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, ductal or lobular carcinoma in situ of the breast, or other malignancies from which the patient has been continuously disease-free for ≥ 5 years
- Patients must not have any clinically significant cardiovascular disease including the following:
- Myocardial infarction or ventricular tachyarrhythmia within 6 months
- Prolonged QTc >480 msec (Fridericia correction)
- Ejection fraction less than institutional normal
- Major conduction abnormality (unless a cardiac pacemaker is present)
- Patients with any cardiopulmonary symptoms of unknown cause (e.g., shortness of breath, chest pain, etc.) are to be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (EKG) to rule out QTc prolongation
- Patients with underlying cardiopulmonary dysfunction are excluded from the study
- No uncontrolled hypertension, defined as systolic blood pressure ≥ 150 mm Hg or diastolic blood pressure ≥ 90 mm Hg
- Hypertension that is adequately controlled with medication allowed
- No QTc prolongation, defined as a QTc interval ≥ 450 msecs
- No concurrent serious illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics
- No psychiatric illness or social situation that would limit compliance with study requirements
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from prior therapy
- No prior treatment with targeted therapies directed to C-KIT/PDGFR (e.g., imatinib mesylate or sunitinib malate)
- Prior limb perfusion allowed
- Prior systemic therapy allowed
- At least 4 weeks since prior chemotherapy or immunotherapy
- Prior adjuvant or neoadjuvant chemotherapy or immunotherapy allowed
- At least 4 weeks since prior radiotherapy
- No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (i.e., phenytoin, carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John wort)