RATIONALE: Drugs such as BMS-275291 may stop the growth of Kaposi's sarcoma by stopping blood flow to the tumor. PURPOSE: Phase I/II trial to study the effectiveness of BMS-275291 in treating patients who have HIV -related Kaposi's sarcoma.

Condition	Treatment or Intervention	Phase
epidemic Kaposi's sarcoma recurrent Kaposi's sarcoma	Procedure: biological response modifier therapy  Procedure: growth factor antagonist therapy  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Drug: BMS-275291	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. Determine whether the change in percent of apoptotic cells on tumor biopsies before and after treatment with BMS-275291 is a valid endpoint in patients with HIV-related Kaposi's sarcoma. II. Determine the safety and tolerability of this drug in these patients. III. Determine the antitumor effects of this drug in these patients. IV. Determine the effect of this drug on overall quality of life and tumor-specific symptoms in these patients. V. Determine the effect of this drug on CD4 and CD8 cell counts and percentages and HIV viral load in these patients. VI. Determine the effect of this drug on human herpes virus-8 (HHV-8) viral load and correlate HHV-8 viral burden, tumor stage, and prognosis in these patients. VII. Determine the peak plasma concentration of this drug in these patients.

PROTOCOL OUTLINE: This is a dose-escalation, multicenter study. Patients receive oral BMS-275291 1-2 times daily. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 6 patients receive escalating doses of BMS-275291 until the recommended phase II dose (RPTD) is determined. The RPTD is the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity and more than 1 of 6 patients experiences clinical response or at least 5 of 6 patients demonstrate biologic activity. An additional 29 patients are treated at the RPTD. Quality of life is assessed on day 15 of the first course and then every 28 days thereafter. Patients are followed for at least 1 month.

PROJECTED ACCRUAL: Approximately 24-59 patients will be accrued for this study within 12 months.

Ages Eligible for Study:  16 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Histologically confirmed Kaposi's sarcoma (KS) with serologically documented HIV infection

No symptomatic visceral KS requiring cytotoxic therapy unless refractory to or intolerant of all currently approved agents for visceral KS

At least 5 measurable lesions

• No prior local therapy to any indicator lesion unless clear progression has taken place since treatment

--Prior/Concurrent Therapy--

Biologic therapy: At least 3 weeks since prior biologic therapy for KS and recovered

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy for KS and recovered
• No concurrent systemic chemotherapy for KS

Endocrine therapy: No concurrent corticosteroids except replacement doses

Radiotherapy:

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy for KS and recovered

Surgery: See Disease Characteristics

Other:

• All antiretroviral therapy must be at a stable dose for at least the past 4 weeks and during treatment
• At least 3 weeks since prior local therapy for KS and recovered
• At least 3 weeks since prior investigational therapy for KS and recovered
• At least 14 days since prior acute treatment of infections other than thrush and genital herpes
• Recovered from toxic effects of any other prior KS treatment
• No other concurrent investigational drugs except investigational new drug (IND)-available antiretroviral agents
• No other concurrent KS-specific treatment

--Patient Characteristics--

Age: 16 and over

Performance status: Karnofsky 60-100%

Life expectancy: At least 3 months

Hematopoietic:

• Absolute neutrophil count at least 750/mm3
• Platelet count at least 75,000/mm3
• Hemoglobin at least 8 g/dL

Hepatic:

• Bilirubin no greater than 1.0 times upper limit of normal (ULN) (no greater than 3.5 mg/dL if secondary to indinavir therapy provided direct bilirubin normal)
• AST and ALT no greater than 3 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN OR
• Creatinine clearance greater than 60 mL/min

Other:

• No acute, active opportunistic infection within the past 14 days except oral thrush or genital herpes
• No other serious medical illness within the past 14 days
• No other malignancy requiring cytotoxic therapy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study

Illinois
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611-3013,  United States
Missouri
      Washington University School of Medicine, Saint Louis,  Missouri,  63110,  United States
New York
      Herbert Irving Comprehensive Cancer Center, New York,  New York,  10032,  United States

Study chairs or principal investigators

Jamie Hayden Von Roenn,  Study Chair,  AIDS Associated Malignancies Clinical Trials Consortium   

Study ID Numbers:  CDR0000068885; AMC-024; CPMC-IRB-13985
Record last reviewed:  August 2003
Last Updated:  October 13, 2004
Record first received:  September 13, 2001
ClinicalTrials.gov Identifier:  NCT00024024
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08