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

Sarcoma Clinical Trial

Official title:

A Phase II Trial Of Imatinib Mesylate (Gleevec) In Patients With HIV Related Kaposi's Sarcoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00090987
• Other study ID #: AMC-042
• Secondary ID: U01CA070019CDR00
• Status: Completed
• Phase: Phase 2
• Start date: June 2005
• Est. completion date: December 2009

Study information

• Verified date: May 2018
• Source: AIDS Malignancy Consortium
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Sarcoma
• Sarcoma, Kaposi

Intervention

Drug:
• imatinib mesylate
400 mg orally once a day for up to 6 months.

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Moores UCSD Cancer Center	La Jolla	California
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida
United States	Memorial Sloan - Kettering Cancer Center	New York	New York
United States	Desert Regional Medical Center Comprehensive Cancer Center	Palm Springs	California
United States	Joan Karnell Cancer Center at Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
AIDS Malignancy Consortium	National Cancer Institute (NCI), The EMMES Corporation

Country where clinical trial is conducted

United States, 

References & Publications (3)

Berman E, Nicolaides M, Maki RG, Fleisher M, Chanel S, Scheu K, Wilson BA, Heller G, Sauter NP. Altered bone and mineral metabolism in patients receiving imatinib mesylate. N Engl J Med. 2006 May 11;354(19):2006-13. — View Citation

Kerkelä R, Grazette L, Yacobi R, Iliescu C, Patten R, Beahm C, Walters B, Shevtsov S, Pesant S, Clubb FJ, Rosenzweig A, Salomon RN, Van Etten RA, Alroy J, Durand JB, Force T. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med. 2006 Aug;12(8):908-16. Epub 2006 Jul 23. — View Citation

Koon HB, Krown SE, Lee JY, Honda K, Rapisuwon S, Wang Z, Aboulafia D, Reid EG, Rudek MA, Dezube BJ, Noy A. Phase II trial of imatinib in AIDS-associated Kaposi's sarcoma: AIDS Malignancy Consortium Protocol 042. J Clin Oncol. 2014 Feb 10;32(5):402-8. doi: 10.1200/JCO.2012.48.6365. Epub 2013 Dec 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients Who Achieve a Clinical Response	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	20-24 weeks
Secondary	Inhibition of Platelet-derived Growth Factor-receptor as Assessed by Immunohistochemistry		12 months
Secondary	Cytokine Profiles Before and After Imatinib Therapy		12 months
Secondary	Pharmacokinetic Profile of Imatinib and Antiretrovirals		12 months
Secondary	Mechanisms of Primary and Secondary Resistance to Imatinib Therapy	Mutations in the juxtamembrane or kinase membrane of the c-kit or PDGF receptors at baseline or time of progression	12 months
Secondary	Viral Transcription Profile of Kaposi's Sarcoma-associated Herpesvirus		12 months