Imatinib Mesylate in Treating Patients With HIV-Related Kaposi's Sarcoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier:
NCT00090987
First received: September 7, 2004
Last updated: December 1, 2011
Last verified: December 2011
  Purpose

RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase II trial is studying how well imatinib mesylate works in treating patients with HIV-related Kaposi's sarcoma.


Condition Intervention Phase
Sarcoma
Drug: imatinib mesylate
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 II Trial Of Imatinib Mesylate (Gleevec) In Patients With HIV Related Kaposi's Sarcoma

Resource links provided by NLM:


Further study details as provided by AIDS Malignancy Clinical Trials Consortium:

Primary Outcome Measures:
  • Proportion of Patients Who Achieve a Clinical Response [ Time Frame: 20-24 weeks ] [ Designated as safety issue: No ]
    Clinical response = Complete Response (absence of residual disease) or Partial Response defined as no new lesions (skin or oral), or no new visceral sites of involvement (or the appearance or worsening of tumor-associated edema or effusions); AND 50% or greater decrease in the number of lesions lasting for >4 weeks; OR Complete flattening of at least 50% of all previously raised lesions OR A 50% decrease in the sum of the products of the largest perpendicular diameters of the marker lesions


Secondary Outcome Measures:
  • Inhibition of Platelet-derived Growth Factor-receptor as Assessed by Immunohistochemistry [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Cytokine Profiles Before and After Imatinib Therapy [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Pharmacokinetic Profile of Imatinib and Antiretrovirals [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Mechanisms of Primary and Secondary Resistance to Imatinib Therapy [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Mutations in the juxtamembrane or kinase membrane of the c-kit or PDGF receptors at baseline or time of progression

  • Viral Transcription Profile of Kaposi's Sarcoma-associated Herpesvirus [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: June 2005
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Imatinib mesylate
Imatinib mesylate (Gleevec) taken 400 mg orally once a day for up to 6 months
Drug: imatinib mesylate
400 mg orally once a day for up to 6 months.
Other Name: Gleevec

Detailed Description:

OBJECTIVES:

Primary

  • Determine clinical response in patients with HIV-related Kaposi's sarcoma treated with imatinib mesylate.

Secondary

  • Determine the inhibition of platelet-derived growth factor receptors, as determined by immunohistochemistry, in patients treated with this drug.
  • Determine cytokine profiles before and after treatment with this drug in these patients.
  • Determine the pharmacokinetic profile of this drug and antiretrovirals in these patients.
  • Determine mechanisms of primary and secondary resistance to this drug in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral imatinib mesylate once daily. Treatment continues for up to 1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 1 year.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed Kaposi's sarcoma (KS) involving at least 1 of the following areas:

    • Skin
    • Lymph nodes
    • Oral cavity
    • Gastrointestinal tract*
    • Lungs* NOTE: *Must be asymptomatic or minimally symptomatic AND does not require systemic cytotoxic therapy
  • Serological documentation of HIV infection, as evidenced by positive enzyme-linked immunosorbent assay (ELISA), Western Blot test, or other federally approved licensed HIV test
  • At least 5 measurable, non-irradiated, cutaneous indicator lesions

    • Patients must have 3 lesions at least 5 x 5 mm that are accessible for 4 mm punch biopsy

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Karnofsky 60-100%

Life expectancy

  • At least 3 months

Hematopoietic

  • Hemoglobin ≥ 8.0 g/dL
  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 75,000/mm^3

Hepatic

  • AST and ALT ≤ 2.5 times upper limit of normal
  • Bilirubin normal

    • Patients with elevated bilirubin secondary to indinavir or atazanavir allowed provided total bilirubin is < 3.5 mg/dL AND direct bilirubin is normal
  • No acute or known chronic liver disease (e.g., chronic active hepatitis or cirrhosis)

    • Hepatitis C infection with minimal or no fibrosis on liver biopsy allowed

Renal

  • Creatinine ≤ 1.5 mg/dL OR
  • Creatinine clearance > 60 mL/min

Cardiovascular

  • No New York Heart Association class III or IV cardiac disease
  • No congestive heart failure
  • No myocardial infarction within the past 6 months

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for 3 months after study participation
  • No concurrent active opportunistic infection
  • No other severe and/or life-threatening medical disease
  • No other malignancy within the past 5 years except clinically insignificant malignancy not requiring active intervention, basal cell skin cancer, or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • More than 4 weeks since prior biologic therapy for KS
  • More than 2 weeks since prior granulocyte colony-stimulating factor
  • No concurrent biologic agents for KS

Chemotherapy

  • More than 4 weeks since prior chemotherapy for KS (6 weeks for nitrosoureas or mitomycin)
  • No concurrent chemotherapy for KS, including systemic cytotoxic chemotherapy

Endocrine therapy

  • No concurrent systemic corticosteroid therapy except replacement doses

Radiotherapy

  • See Disease Characteristics
  • More than 4 weeks since prior radiotherapy for KS
  • No concurrent radiotherapy for KS

Surgery

  • More than 2 weeks since prior major surgery

Other

  • No prior imatinib mesylate
  • More than 60 days since prior local therapy to any KS indicator lesion unless the lesion has progressed since treatment
  • More than 4 weeks since prior investigational therapy for KS
  • More than 4 weeks since other prior therapy for KS
  • More than 14 days since prior acute treatment for an infection or other serious medical illness
  • No concurrent warfarin
  • No concurrent grapefruit juice
  • No other concurrent therapy for KS
  • No other concurrent investigational drugs
  • Concurrent antiretroviral therapy required except for patients who have exhausted all available treatment options
  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: NCT00090987

Locations
United States, California
Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
Desert Regional Medical Center Comprehensive Cancer Center
Palm Springs, California, United States, 92262
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital
Saint Louis, Missouri, United States, 63110
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Memorial Sloan - Kettering Cancer Center
New York, New York, United States, 10021
United States, Ohio
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
United States, Pennsylvania
Joan Karnell Cancer Center at Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19106
United States, Washington
Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center
Seattle, Washington, United States, 98101
Sponsors and Collaborators
AIDS Malignancy Clinical Trials Consortium
Investigators
Study Chair: Ariela Noy, MD Memorial Sloan-Kettering Cancer Center
Study Chair: Henry Koon, MD Beth Israel Deaconess Medical Center
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier: NCT00090987     History of Changes
Other Study ID Numbers: CDR0000380955, U01CA070019, AMC-042
Study First Received: September 7, 2004
Results First Received: May 25, 2011
Last Updated: December 1, 2011
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by AIDS Malignancy Clinical Trials Consortium:
AIDS-related Kaposi sarcoma
recurrent Kaposi sarcoma

Additional relevant MeSH terms:
Sarcoma, Kaposi
Sarcoma
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Vascular Tissue
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014