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Imatinib Mesylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by National Cancer Institute (NCI).   Recruitment status was  Recruiting

First Received on May 3, 2007.   Last Updated on August 24, 2010   History of Changes
Sponsor: Memorial Sloan-Kettering Cancer Center
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00470470
  Purpose

RATIONALE: Imatinib mesylate 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 imatinib mesylate works in treating patients with stage III or stage IV melanoma that cannot be removed by surgery.


Condition Intervention Phase
Melanoma (Skin)
Drug: imatinib mesylate
Genetic: comparative genomic hybridization
Genetic: gene expression analysis
Genetic: mutation analysis
Genetic: protein expression analysis
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Procedure: biopsy
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Imatinib Mesylate (STI571;NSC#716051:IND 61135) in Patients With Inoperable AJCC Stage III or IV Melanoma Harboring Somatic Alterations of C-KIT

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Objective response rate (complete response and partial response) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progression [ Designated as safety issue: No ]
  • Protein expression by IHC [ Designated as safety issue: No ]
  • Gene amplification by FISH [ Designated as safety issue: No ]
  • Gene amplification and gene copy number by comparative genomic hybridization [ Designated as safety issue: No ]
  • c-KIT DNA sequencing [ Designated as safety issue: No ]
  • Correlation of IHC criteria with sequencing or amplification results [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: April 2007
Estimated Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the overall objective response rate (complete response and partial response) in patients with inoperable stage III or IV melanoma harboring somatic alterations in c-KIT treated with imatinib mesylate.

Secondary

  • Determine the time to progression in patients treated with this drug.
  • Determine if c-KIT mutational status by DNA sequencing, DNA copy number status by FISH or comparative genomic hybridization, and/or protein expression by IHC can best predict clinical benefit from imatinib mesylate.

OUTLINE: This is a multicenter study. Patients are stratified according to true amplification of c-KIT by FISH vs mutations by DNA sequencing.

Patients receive oral imatinib mesylate twice daily for up to 12 weeks in the absence of disease progression or unacceptable toxicity.

Tumor tissue samples or unstained tissue slides/paraffin blocks may be collected. c-KIT is evaluated by IHC and comparative genomic hybridization.

After completion of study treatment, patients are followed up periodically.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed inoperable stage III or IV melanoma that began on acral skin or mucosa

    • Patients with cutaneous melanoma that began on sun exposed sites of the skin and whose pathology demonstrates signs of sun damage (solar elastosis) involving the skin surrounding their primary melanoma are eligible
  • Must have sufficient tumor tissue available for FISH and DNA sequencing

    • Patients must have either a true amplification of 4q12 or a detectable mutation of c-KIT
    • If no banked tumor tissue is available, or if the available banked tumor tissue is insufficient for the necessary testing, then a repeat biopsy procedure will be required to collect the necessary tumor sample
  • Measurable disease according to RECIST criteria
  • No known untreated brain or epidural metastases

    • Brain metastases that have been treated and deemed stable are allowed

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy greater than 3 months
  • WBC ≥ 3,000/mm³
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)

    • Patients with unexplained hyperbilirubinemia that is clinically consistent with an inherited disorder of bilirubin metabolism (e.g., Gilbert's syndrome) may be eligible
  • AST and ALT ≤ 2.5 times ULN (5 times ULN if hepatic metastases are present)
  • Creatinine ≤ 1.5 times ULN
  • PT and PTT ≤ 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception before and during study participation
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to imatinib mesylate
  • No concurrent uncontrolled illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia resulting in hemodynamic instability
    • Intestinal malabsorption disorders
    • Psychiatric illness or social situations that would limit study compliance

PRIOR CONCURRENT THERAPY:

  • Recovered to grade 1 from all prior therapies with the exception of alopecia
  • At least 2 weeks since prior radiotherapy (≤ 3,000 cGy to fields including substantial marrow)
  • At least 2 weeks since prior isolated limb infusion or perfusion (must have evidence of progression despite this therapy)
  • At least 2 weeks since prior chemotherapy
  • No more than 2 prior chemotherapy regimen for metastatic melanoma
  • Prior therapies with vaccines, targeted agents not believed to affect the kit proteins, cytokines, interferon-α, or intratumoral injections will NOT be considered prior therapy unless administered with a chemotherapy drug
  • No prior therapy with an inhibitor of the kit protein
  • No other concurrent investigational agents
  • No other concurrent anticancer agents or therapies
  • No concurrent antiretroviral therapy for HIV-positive patients
  • No concurrent inhibitors of CYP3A4, including any of the following:

    • Fluconazole, itraconazole, ketoconazole, macrolide antibiotics (azithromycin, clarithromycin, erythromycin, troleandomycin), midazolam, nifedipine, verapamil, diltiazem, terfenadine, cyclosporine and cisapride
    • Herbal extracts and tinctures with CYP3A4 inhibitory activity, including the following:

      • Hydrastis canadensis (goldenseal), Hypericum perforatum (St. John's wort), Uncaria tomentosa (cat's claw), Echinacea angustifolia roots, Trifolium pratense (wild cherry), Matricaria, chamomilla (chamomile), Glycyrrhiza glabra (licorice), dillapiol, hypericin, and naringenin
  • No concurrent inducers of CYP3A4, including any of the following:

    • Carbamazepine, phenobarbital, phenytoin, and rifampin
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00470470

Locations
United States, California
University of California Los Angeles Medical Center Recruiting
Los Angeles, California, United States, 90024
Contact: Bartosz Chmielowski, MD     310-206-1214        
United States, Florida
Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center Recruiting
Miami Beach, Florida, United States, 33140
Contact: Jose Lutzky, MD     305-535-3305        
Palm Beach Cancer Institute - West Palm Beach Recruiting
West Palm Beach, Florida, United States, 33401
Contact: Neal E. Rothschild, MD     561-366-4131        
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Richard Carvajal, MD     212-639-5096        
Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: Howard L. Kaufman, MD     212-241-4757        
New York Presbyterian Hospital-Cornell Medical Center Recruiting
New York, New York, United States, 10021
Contact: Tsiporah B. Shore, MD, FRCP, FACP     212-746-2646        
NYU Cancer Institute at New York University Medical Center Recruiting
New York, New York, United States, 10016
Contact: Anna Pavlick, MD     212-731-5431     anna.pavlick@nyumc.org    
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Richard Carvajal, MD Memorial Sloan-Kettering Cancer Center
Principal Investigator: Paul B. Chapman, MD Memorial Sloan-Kettering Cancer Center
Principal Investigator: Gary K. Schwartz, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: David Paul Kelsen, Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00470470     History of Changes
Other Study ID Numbers: CDR0000543404, MSKCC-07014
Study First Received: May 3, 2007
Last Updated: August 24, 2010
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent melanoma
stage IV melanoma
acral lentiginous malignant melanoma
stage IIIA melanoma
stage IIIB melanoma
stage IIIC melanoma

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
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 22, 2012