BMS-275291 in Treating Patients With HIV-Related Kaposi's Sarcoma

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

Detailed Description
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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. 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.

Official Title
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A Phase I-II Trial Of BMS-275291 In Patients With HIV-Related Kaposi's Sarcoma

Conditions
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Sarcoma

Intervention / Treatment
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* Drug: rebimastat


Participation Criteria
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Eligibility Criteria
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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 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 PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 weeks since prior biologic therapy for KS and recovered Chemotherapy: 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: At least 3 weeks since prior radiotherapy for KS and recovered 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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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. | Drug: rebimastat<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AIDS-related Kaposi sarcoma, recurrent Kaposi sarcoma