Treatment With Dasatinib in Patients With Acral Lentiginous, Mucosal, or Chronic Sun-damaged Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Dasatinib; Surgical Resection
Intervention description: 100 mg daily.; Complete surgical resection of tumor(s).
Intervention MeSH terms: Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Acral lentiginous melanoma; Mucosal melanoma; Chronic sun-damaged melanoma; Surgically removed tumor; biopsied; Sprycel; Dasatinib

Summary:

      The goal of this clinical research study is to compare how the drug Sprycel (dasatinib) can
      help to control the tumor in Patients With Acral Lentiginous, Mucosal, or Chronic Sun-damaged
      Melanoma. The safety of this drug will also be studied.

      Objectives:

      Primary Objectives:

      1. To compare the biological response of tumors With and Without Resectable Tumors from
      patients with acral, or mucosal melanomas after treatment with dasatinib.

      Secondary Objectives:

        1. To assess the safety and tolerability of dasatinib in this patient population

           Completely Resectable Acral, Chronic Sun-damaged (CSD), and Mucosal Melanoma:

        2. To assess the median time to recurrence and overall survival of patients with completely
           resectable acral, CSD, and mucosal melanoma treated with dasatinib

        3. To assess whether FDG-avidity and KIT phosphorylation responses after treatment with
           dasatinib predicts prolonged time to recurrence and/or overall survival in patients with
           completely resectable acral, CSD, and mucosal melanomas

           Not Completely Resectable Acral, CSD, and Mucosal Melanoma:

        4. To assess the response rate, progression free survival, and overall survival of patients
           with acral, CSD, and mucosal melanoma treated with dasatinib

        5. To assess whether FDG-avidity and KIT phosphorylation responses after treatment with
           dasatinib predicts response rate, progression free survival, and/or overall survival in
           patients with acral, CSD, and mucosal melanomas
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients must have primary, recurrent or metastatic melanoma with one of the following
             pathology or characteristics: i) acral lentiginous melanoma ii) mucosal melanoma iii)
             any known KIT mutation.

          2. (Continued 1) If 20 patients without tumors harboring exon 11 or 13 KIT mutation are
             enrolled and treated before the completion of the patient accrual of 30, only those
             with tumors harboring exon 11 or 13 KIT mutation will be enrolled. Likewise, if 10
             patients with tumors harboring exon 11 or 13 KIT mutation are enrolled and treated
             before the completion of the patient accrual of 30, only those without tumors
             harboring exon 11 or 13 KIT mutation will then be enrolled.

          3. Patients must have measurable disease by 18-Fluoro-deoxyglucose positron emission
             tomography (FDG-PET) (with or without computed tomography (CT)) defined as having a
             maximum standardized uptake value (SUVmax) of 3 and SUVmax ofat least 2 fold greater
             than background.

          4. Patients scheduled for FDG-PET should have uptake of the tracer in at least one lesion
             (tumor-to-muscle ratio >2) in the baseline PET/CT scan in order to be eligible for the
             follow-up FDG PET scans.

          5. Patient must have surgically resectable melanoma lesion(s) or biopsiable lesion(s)
             which are amenable to 2 separate biopsy procedures by a core needle or excision.

          6. Age >/= 18 years.

          7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

          8. Adequate Organ Function: a. Total bilirubin < 2.0 times the institutional Upper Limit
             of Normal (ULN), b.Hepatic enzymes (aspartate transaminase, alanine transaminase (AST,
             ALT) ) </= 2.5 times the institutional ULN, c. Serum Creatinine < 1.5 time the
             institutional ULN, d.Neutrophil count >/= 1500; Platelets >/= 75,000;

          9. Ability to take oral medication (dasatinib must be swallowed whole)

         10. Concomitant Medications: a. Patient agrees to discontinue St. Johns Wort while
             receiving dasatinib therapy (discontinue St. Johns Wort at least 5 days before
             starting dasatinib), b.Patient agrees that IV bisphosphonates will be withheld for the
             first 8 weeks of dasatinib therapy due to risk of hypocalcemia.

         11. Women of childbearing potential (WOCBP) must have: a) A negative serum or urine
             pregnancy test (sensitivity 25 IU human chorionic gonadotropin (HCG/L) within 72 hours
             prior to the start of study drug administration b) Persons of reproductive potential
             must agree to use and utilize an adequate method of contraception throughout treatment
             and for at least 4 weeks after study drug is stopped. Prior to study enrollment, women
             of childbearing potential must be advised of the importance of avoiding pregnancy
             during trial participation and the potential risk factors for an unintentional
             pregnancy.

         12. Signed written informed consent including a Health Insurance Portability and
             Accountability Act (HIPAA) form according to institutional guidelines

        Exclusion Criteria:

          1. No other malignancy which required radiotherapy or systemic treatment within the past
             5 years.

          2. Concurrent medical condition which may increase the risk of toxicity, including: a.
             Pleural or pericardial effusion of any grade.

          3. Cardiac Symptoms; any of the following should be considered for exclusion: a.
             Uncontrolled angina, congestive heart failure or MI within (6 months), b. Diagnosed
             congenital long QT syndrome, c. Any history of clinically significant ventricular
             arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de
             pointes), d. Prolonged corrected QT interval (QTc) interval on pre-entry
             electrocardiogram (> 480 msec) [or > 500 msec for patients with a bundle branch
             block]), e. Subjects with hypokalemia or hypomagnesemia if it cannot be corrected
             prior to dasatinib administration.

          4. History of significant bleeding disorder unrelated to cancer, including: a. Diagnosed
             congenital bleeding disorders (e.g., von Willebrand's disease), b. Diagnosed acquired
             bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies), c.
             Ongoing or recent (</= 3 months) significant gastrointestinal bleeding.

          5. Concomitant Medications, any of the following should be considered for exclusion: a.
             Category I drugs that are generally accepted to have a risk of causing Torsades de
             Pointes including: (Patients must discontinue drug 7 days prior to starting
             dasatinib), I. quinidine, procainamide, disopyramide, II. amiodarone, sotalol,
             ibutilide, dofetilide, III. erythromycin, clarithromycin, IV. chlorpromazine,
             haloperidol, mesoridazine, thioridazine, pimozide V. cisapride, bepridil, droperidol,
             methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine,
             sparfloxacin, lidoflazine.

          6. Women who: a. are unwilling or unable to use an acceptable method to avoid pregnancy
             for the entire study period and for at least 4 weeks after cessation of study drug,
             or, b. have a positive pregnancy test at baseline, or, c. are pregnant or
             breastfeeding,

          7. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
             treatment of either a psychiatric or physical (e.g., infectious) illness

          8. No active, untreated brain metastases. Patients with known brain metastases will be
             included if the brain metastases have been treated and stable for at least 3 months
             without the use of steroid

          9. HIV-positive patients on combination antiretroviral therapy are ineligible because of
             the potential for pharmacokinetic interactions with dasatinib. In addition, these
             patients are at increased risk of lethal infections when treated with
             marrow-suppressive therapy. Appropriate studies will be undertaken in patients
             receiving combination antiretroviral therapy when indicated.

         10. Patients with melanoma harboring BRAF mutation. If BRAF mutation is not known at the
             time of screening, patients will still be eligible