Clinical trial NCT00090987: Imatinib Mesylate in Treating Patients With HIV-Related Kaposi's Sarcoma
Official title: A Phase II Trial Of Imatinib Mesylate (Gleevec) In Patients With HIV Related Kaposi's Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma
Keywords: AIDS-related Kaposi sarcoma
recurrent Kaposi sarcoma
Lead sponsor: AIDS Malignancy Consortium
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: The Emmes Company, LLC
First posted: 2004-09-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Proportion of Patients Who Achieve a Clinical Response
timeFrame: 20-24 weeks
Secondary outcomes:
measure: Inhibition of Platelet-derived Growth Factor-receptor as Assessed by Immunohistochemistry
timeFrame: 12 months
measure: Cytokine Profiles Before and After Imatinib Therapy
timeFrame: 12 months
measure: Pharmacokinetic Profile of Imatinib and Antiretrovirals
timeFrame: 12 months
measure: Mechanisms of Primary and Secondary Resistance to Imatinib Therapy
timeFrame: 12 months
measure: Viral Transcription Profile of Kaposi's Sarcoma-associated Herpesvirus
timeFrame: 12 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center at UCLA
state: California
city: Palm Springs
country: United States
facility: Desert Regional Medical Center Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center - Miami
state: Florida
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital
state: Missouri
city: Bronx
country: United States
facility: Albert Einstein Cancer Center at Albert Einstein College of Medicine
state: New York
city: New York
country: United States
facility: Memorial Sloan - Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Joan Karnell Cancer Center at Pennsylvania Hospital
state: Pennsylvania
city: Seattle
country: United States
facility: Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center
state: Washington
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Ariela Noy, MD
role: STUDY_CHAIR
affiliation: Beth Israel Deaconess Medical Center
name: Henry Koon, MD
role: STUDY_CHAIR
References:
citation: 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. doi: 10.1056/NEJMoa051140.
citation: Kerkela 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. doi: 10.1038/nm1446. Epub 2006 Jul 23.
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.