A Phase 2 Study of Dasatinib in Advanced Melanoma
18 Years
N/A
Both
Recurrent Melanoma, Stage IIIA Melanoma, Stage IIIB Melanoma, Stage IIIC Melanoma, Stage IV Melanoma
Trial Information
A Phase 2 Study of Dasatinib in Advanced Melanoma
PRIMARY OBJECTIVES:
I. Determine the objective response rate in patients with stage III unresectable or stage IV
melanoma treated with dasatinib.
II. Determine the progression-free survival of patients treated with this drug.
SECONDARY OBJECTIVES:
I. To assess the expression of targets of Dasatinib prior to treatment by obtaining
pre-treatment biopsies or examining paraffin-embedded tissues from previous tumor
resections.
II. In selected patients (approximately 5-10) where tumor tissue is available pre-treatment
and can be obtained post-treatment with Dasatinib (21 days after initiation of therapy), to
determine if Dasatinib induces changes in expression of selected targets and downstream
mediators, including MEK, ERK and RSK-1.
III. To assess toxicity.
OUTLINE:
Patients receive oral dasatinib twice daily on days 1-28. Courses repeat every 28 days in
the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
Inclusion Criteria:
- Histologically confirmed stage III unresectable or stage IV melanoma
- Measurable disease
- Must have evidence of tumor growth or new lesions within the past 6 months
- No large pleural effusions
- No known brain metastases or leptomeningeal metastases
- Previously treated brain metastases allowed provided there is no requirement for
steroids AND no evidence of progression for ≥ 8 weeks after treatment
- ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
- Life expectancy > 3 months
- WBC ≥ 3,000/mm³
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 9.0 g/dL (transfusions allowed)
- Bilirubin ≤ 1.5 mg/mL
- AST and ALT ≤ 2.5 times upper limit of normal (ULN)
- PT/INR and PTT normal
- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
- No medical condition that may affect the ability to swallow and retain dasatinib
tablets, including any of the following:
- Gastrointestinal tract disease resulting in an inability to take oral medication
- Requirement for IV alimentation
- Prior surgical procedures affecting absorption
- Active peptic ulcer disease
- No clinically significant cardiovascular disease, including any of the following:
- Myocardial infarction or ventricular tachyarrhythmia within the past 6 months
- Prolonged QTc > 480 msec
- Major conduction abnormality (unless a cardiac pacemaker is present)
- No uncontrolled intercurrent illness including, but not limited to, any of the
following:
- Ongoing or active infection
- History of significant congenital or acquired bleeding disorder, including any
of the following:
- Von Willebrand's disease
- Antifactor VIII antibodies
- Dyspnea at rest or with minimal exertion
- Uncontrolled seizure disorder
- Psychiatric illness or social situations that would preclude study compliance
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other active malignancy within the past 3 years except curatively treated stage I
malignancies or resected skin carcinomas
- Recovered from prior therapy
- Prior adjuvant therapy for stage II or III melanoma allowed
- No prior cytotoxic therapy for metastatic melanoma
- No prior dasatinib or other inhibitors of src, bcr-abl, c-Kit, EPHA2, and PDGFRβ
- No more than 2 prior immunomodulator therapies for metastatic melanoma
- At least 1 week since prior and no concurrent warfarin or other anticoagulants or
medications that inhibit platelet function (including acetylsalicylic acid)
- At least 1 week since prior and no concurrent steroids or other immunosuppressive
agents
- Concurrent steroids to treat induced pleural effusions allowed
- At least 3 weeks since prior immunomodulators including, but not limited to, any of
the following:
- Aldesleukin
- Cancer vaccines
- T-cell-activating monoclonal antibodies
- At least 4 weeks since prior radiotherapy
- Prior palliative radiotherapy to a single site of disease allowed (tumor is not
considered evaluable for response unless there is tumor progression at the site
of radiation)
- More than 7 days since prior and no concurrent CYP3A4 inhibitors
- At least 7 days since prior and no concurrent agents with proarrhythmic potential
- No other concurrent investigational agents
- No other concurrent anticancer agents or therapies
- No concurrent enzyme-inducing anticonvulsant agents
- No concurrent grapefruit or grapefruit juice
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No concurrent CYP3A4 inducers
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Objective response rate (partial response and complete response) as measured by RECIST criteria
Outcome Description:
Only those patients who have measurable disease present at baseline, have received at least one course of therapy, and have had their disease re-evaluated will be considered evaluable for response. A Simon's optimum two-stage design will be used.
Outcome Time Frame:
After every 8 weeks (or 2 courses), assessed up to 4 weeks after completion of treatment
Safety Issue:
No
Principal Investigator
Harriet Kluger
Investigator Role:
Principal Investigator
Investigator Affiliation:
Yale University
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00219
NCT ID:
NCT00436605
Start Date:
December 2006
Completion Date:
Related Keywords:
- Recurrent Melanoma
- Stage IIIA Melanoma
- Stage IIIB Melanoma
- Stage IIIC Melanoma
- Stage IV Melanoma
- Melanoma
Name | Location |
|---|---|
| Yale University | New Haven, Connecticut 06520 |
| Masonic Cancer Center, University of Minnesota | Minneapolis, Minnesota 55455 |
