Dasatinib in Treating Patients With Stage III Melanoma That Cannot Be Removed By Surgery or Stage IV Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00436605
First received: February 15, 2007
Last updated: April 29, 2014
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Recurrent Melanoma
Stage IIIA Melanoma
Stage IIIB Melanoma
Stage IIIC Melanoma
Stage IV Melanoma
Drug: dasatinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Dasatinib in Advanced Melanoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Number of Subjects With Objective Response(Partial Response and Complete Response) as Measured by RECIST Criteria [ Time Frame: After every 8 weeks (or 2 courses), assessed up to 4 weeks after completion of treatment ] [ Designated as safety issue: No ]
    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.

  • Progression-free Survival [ Time Frame: Time from start treatment to time of progression, assessed up to 6 months ] [ Designated as safety issue: No ]
    Progression will be evaluated in this study using the new international criteria proposed by the RECIST Committee. A Simon's optimum two-stage design will be used


Enrollment: 39
Study Start Date: December 2006
Study Completion Date: November 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (kinase inhibitor therapy)
Patients receive oral dasatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: dasatinib
Other Names:
  • BMS-354825
  • Sprycel

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00436605

Locations
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Investigators
Principal Investigator: Harriet Kluger Yale University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00436605     History of Changes
Other Study ID Numbers: NCI-2009-00219, NCI-2009-00219, CDR0000528937, UMN-2007UC009, YALE-HIC-0608001765, HIC#0608001765, 7758, P30CA016359
Study First Received: February 15, 2007
Results First Received: December 5, 2013
Last Updated: April 29, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Dasatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 27, 2014