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

AIDS Malignancy Consortium

Status and phase: Completed; Phase 2

Conditions: Sarcoma

Treatments: Drug: imatinib mesylate

Study type: Interventional

Funder types: NETWORK; Industry; NIH

Identifiers

NCT00090987

U01CA070019 (U.S. NIH Grant/Contract)

CDR0000380955 (Other Identifier)

AMC-042

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Imatinib mesylate

Experimental group

Description:

Imatinib mesylate (Gleevec) taken 400 mg orally once a day for up to 6 months

Treatment:

Drug: imatinib mesylate