Clinical Trials /

Dasatinib in Treating Patients With Locally Advanced or Metastatic Mucosal Melanoma, Acral Melanoma, or Vulvovaginal Melanoma That Cannot Be Removed By Surgery

NCT00700882

Description:

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well dasatinib works in treating patients with locally advanced or metastatic mucosal melanoma or acral melanoma.

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Dasatinib</span> in Treating Patients With Locally Advanced or Metastatic Mucosal <span class="go-doc-concept go-doc-disease">Melanoma</span>, Acral <span class="go-doc-concept go-doc-disease">Melanoma</span>, or Vulvovaginal <span class="go-doc-concept go-doc-disease">Melanoma</span> That Cannot Be Removed By Surgery

Title

  • Brief Title: Dasatinib in Treating Patients With Locally Advanced or Metastatic Mucosal Melanoma, Acral Melanoma, or Vulvovaginal Melanoma That Cannot Be Removed By Surgery
  • Official Title: A Phase II Trial of Dasatinib in Patients With Unresectable Locally Advanced or Stage IV Mucosal, Acral and Vulvovaginal Melanomas
  • Clinical Trial IDs

    NCT ID: NCT00700882

    ORG ID: CDR0000598300

    NCI ID: E2607

    Trial Conditions

    Melanoma (Skin)

    Trial Interventions

    Drug Synonyms Arms
    dasatinib

    Trial Purpose

    RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes
    needed for cell growth.

    PURPOSE: This phase II trial is studying how well dasatinib works in treating patients with
    locally advanced or metastatic mucosal melanoma or acral melanoma.

    Detailed Description

    OBJECTIVES:

    Primary

    - 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.

    Secondary

    - 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.

    Trial Arms

    Name Type Description Interventions

    Eligibility Criteria

    DISEASE CHARACTERISTICS:

    - 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

    PATIENT CHARACTERISTICS:

    - ECOG performance status 0-1

    - WBC 3,000/mm

    - Absolute granulocyte count 1,500/mm

    - Platelet count 100,000/mm

    - 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)

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Objective tumor response rate (complete and partial response)

    Secondary Outcome Measures

    Response duration

    Progression-free survival

    Safety profile

    Trial Keywords

    stage IV melanoma

    acral lentiginous malignant melanoma

    mucosal melanoma

    recurrent melanoma

    stage IIIA melanoma

    stage IIIB melanoma

    stage IIIC melanoma