search
Back to results

Imatinib Mesylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

Primary Purpose

Acral Lentiginous Malignant Melanoma, Recurrent Melanoma, Stage IIIA Melanoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
imatinib mesylate
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acral Lentiginous Malignant Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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 Response Evaluation Criteria in Solid Tumors (RECIST) criteria
  • No known untreated brain or epidural metastases

    • Brain metastases that have been treated and deemed stable are allowed
  • 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 anginapectoris
    • Cardiac arrhythmia resulting in hemodynamic instability
    • Intestinal malabsorption disorders
    • Psychiatric illness or social situations that would limit study compliance
  • 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

Sites / Locations

  • University of California at Los Angeles (UCLA )
  • Mount Sinai Medical Center CCOP
  • Good Samaritan Medical Center
  • Palm Beach Cancer Institute-Main Office
  • New York University Langone Medical Center
  • Mount Sinai Medical Center
  • Memorial Sloan Kettering Cancer Center
  • Weill Medical College of Cornell University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (enzyme inhibitor therapy)

Arm Description

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

Outcomes

Primary Outcome Measures

Objective Response Rate
Response will be evaluated in this study using the new international criteria proposed by the RECIST Committee. A Simon two-stage minimax design will be employed.

Secondary Outcome Measures

Time to Progression
Progression will be evaluated in this study using the new international criteria proposed by the RECIST Committee. Time to progression will be estimated using the Kaplan-Meier method.

Full Information

First Posted
May 3, 2007
Last Updated
December 15, 2014
Sponsor
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00470470
Brief Title
Imatinib Mesylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
October 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVES: I. 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 OBJECTIVES: I. Determine the time to progression in patients treated with this drug. II. Determine if c-KIT mutational status by DNA sequencing, DNA copy number status by fluorescent in situ hybridization (FISH) or comparative genomic hybridization, and/or protein expression by immunohistochemistry (IHC) can best predict clinical benefit from imatinib mesylate. TERTIARY OBJECTIVES: I. To evaluate tumors resistant to small molecule inhibitors of Kit for the development of secondary Kit mutations or for changes in Kit copy number. II. To evaluate for changes in Ki-67, phospho-Akt, phospho-MEK, phospho-S6, phospho STAT3, cleaved caspase 3, IGF-1R, and Kit expression in paired tumor samples obtained from patients treated with a small molecule inhibitor of Kit. III. To analyze baseline and post-resistance blood samples for soluble cKIT levels, soluble VEGFR1, soluble VEGFR2, VEGF, PlGF, FGF, and melanoma inhibitory activity (MIA) levels, and circulating tumor cells. IV. To analyze concomitant samples of blood and tumor for imatinib levels in patients treated with imatinib. OUTLINE: This is a multi-center 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acral Lentiginous Malignant Melanoma, Recurrent Melanoma, Stage IIIA Melanoma, Stage IIIB Melanoma, Stage IIIC Melanoma, Stage IV Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (enzyme inhibitor therapy)
Arm Type
Experimental
Arm Description
Patients receive oral imatinib mesylate twice daily for up to 12 weeks in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
imatinib mesylate
Other Intervention Name(s)
CGP 57148, Gleevec, Glivec
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
Response will be evaluated in this study using the new international criteria proposed by the RECIST Committee. A Simon two-stage minimax design will be employed.
Time Frame
Every 6 weeks for the first 3 courses and then every 12 weeks thereafter
Secondary Outcome Measure Information:
Title
Time to Progression
Description
Progression will be evaluated in this study using the new international criteria proposed by the RECIST Committee. Time to progression will be estimated using the Kaplan-Meier method.
Time Frame
Time from the treatment start to the date of disease progression

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Response Evaluation Criteria in Solid Tumors (RECIST) criteria No known untreated brain or epidural metastases Brain metastases that have been treated and deemed stable are allowed 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 anginapectoris Cardiac arrhythmia resulting in hemodynamic instability Intestinal malabsorption disorders Psychiatric illness or social situations that would limit study compliance 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Carvajal
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California at Los Angeles (UCLA )
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Mount Sinai Medical Center CCOP
City
Miami Beach
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Facility Name
Good Samaritan Medical Center
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33401
Country
United States
Facility Name
Palm Beach Cancer Institute-Main Office
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33401
Country
United States
Facility Name
New York University Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Weill Medical College of Cornell University
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21642685
Citation
Carvajal RD, Antonescu CR, Wolchok JD, Chapman PB, Roman RA, Teitcher J, Panageas KS, Busam KJ, Chmielowski B, Lutzky J, Pavlick AC, Fusco A, Cane L, Takebe N, Vemula S, Bouvier N, Bastian BC, Schwartz GK. KIT as a therapeutic target in metastatic melanoma. JAMA. 2011 Jun 8;305(22):2327-34. doi: 10.1001/jama.2011.746.
Results Reference
derived

Learn more about this trial

Imatinib Mesylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

We'll reach out to this number within 24 hrs