Clinical trial NCT00436605: Dasatinib in Treating Patients With Stage III Melanoma That Cannot Be Removed By Surgery or Stage IV Melanoma
Official title: A Phase 2 Study of Dasatinib in Advanced Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Melanoma
Stage IIIA Melanoma
Stage IIIB Melanoma
Stage IIIC Melanoma
Stage IV Melanoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-02-19
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial is studying how well dasatinib works in treating patients with stage III melanoma that cannot be removed by surgery or stage IV melanoma. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Subjects With Objective Response(Partial Response and Complete Response) as Measured by RECIST Criteria
timeFrame: After every 8 weeks (or 2 courses), assessed up to 4 weeks after completion of treatment
measure: Progression-free Survival
timeFrame: Time from start treatment to time of progression, assessed up to 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
affiliation: Yale University
name: Harriet Kluger
role: PRINCIPAL_INVESTIGATOR
References: