Compounds > n-((2s)-2-mercapto-1-oxo-4-(3-4-4--trimethyl-2-5-dioxo-1-imidazolidinyl)butyl)-l-leucyl-n-3--dimethyl-l-valinamide

n-((2s)-2-mercapto-1-oxo-4-(3-4-4--trimethyl-2-5-dioxo-1-imidazolidinyl)butyl)-l-leucyl-n-3--dimethyl-l-valinamide and Sarcoma--Kaposi

n-((2s)-2-mercapto-1-oxo-4-(3-4-4--trimethyl-2-5-dioxo-1-imidazolidinyl)butyl)-l-leucyl-n-3--dimethyl-l-valinamide has been researched along with Sarcoma--Kaposi* in 1 studies

Trials

1 trial(s) available for n-((2s)-2-mercapto-1-oxo-4-(3-4-4--trimethyl-2-5-dioxo-1-imidazolidinyl)butyl)-l-leucyl-n-3--dimethyl-l-valinamide and Sarcoma--Kaposi

Article	Year
Phase 1/2 trial of BMS-275291 in patients with human immunodeficiency virus-related Kaposi sarcoma: a multicenter trial of the AIDS Malignancy Consortium. Cancer, 2008, Mar-01, Volume: 112, Issue:5 Matrix metalloproteinases (MMPs) are overexpressed in Kaposi sarcoma (KS). The safety and efficacy of a novel, orally bioavailable MMP inhibitor, BMS-275291, was evaluated in patients with human immunodeficiency virus-associated KS and the correlation between changes in the percentage of apoptotic cells in tumor biopsies and response was explored.. Cohorts of 6 patients were to be treated with BMS-275291. The initial cohort received 1200 mg once a day; subsequent doses were to be escalated to 600 mg twice daily and 1200 mg twice daily, or decreased to 600 mg/day. Tumor biopsies for apoptosis assays were collected pretreatment and on Day 29. Prospectively defined dose level adjustments were to be based on dose-limiting toxicity (DLT), tolerability, changes in the percentage of apoptotic cells, and treatment response.. Sixteen patients were enrolled; 15 received the study drug and could be evaluated. The median duration of treatment was 20 weeks (range, 3-54 weeks). A dose of 1200 mg once a day was well tolerated but induced only 1 response. A DLT occurred in 3 patients treated with 600 mg twice daily, and included grade 3 fatigue, grade 3 allergic reaction, and grade 3 arthralgias; 2 responses were noted at this dose level (toxicity was graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]). Based on predetermined endpoints, the trial was closed after accrual of 15 treated patients. Assessment of biologic response for dose escalation/de-escalation decisions utilizing the apoptosis assay was not feasible.. BMS-275291 given at a dose of 600 mg twice daily induced unacceptable toxicity. The better-tolerated schedule of 1200 mg once a day demonstrated inadequate efficacy in patients with human immunodeficiency virus-associated KS. The apoptosis assay was not helpful in predicting response. Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Agents; Apoptosis; CD4-Positive T-Lymphocytes; Drug Administration Schedule; Drug Evaluation; Enzyme Inhibitors; Female; Humans; Imidazoles; Male; Matrix Metalloproteinase Inhibitors; Middle Aged; Sarcoma, Kaposi; Treatment Outcome	2008

Article

Year

Phase 1/2 trial of BMS-275291 in patients with human immunodeficiency virus-related Kaposi sarcoma: a multicenter trial of the AIDS Malignancy Consortium.

Cancer, 2008, Mar-01, Volume: 112, Issue:5

Matrix metalloproteinases (MMPs) are overexpressed in Kaposi sarcoma (KS). The safety and efficacy of a novel, orally bioavailable MMP inhibitor, BMS-275291, was evaluated in patients with human immunodeficiency virus-associated KS and the correlation between changes in the percentage of apoptotic cells in tumor biopsies and response was explored.. Cohorts of 6 patients were to be treated with BMS-275291. The initial cohort received 1200 mg once a day; subsequent doses were to be escalated to 600 mg twice daily and 1200 mg twice daily, or decreased to 600 mg/day. Tumor biopsies for apoptosis assays were collected pretreatment and on Day 29. Prospectively defined dose level adjustments were to be based on dose-limiting toxicity (DLT), tolerability, changes in the percentage of apoptotic cells, and treatment response.. Sixteen patients were enrolled; 15 received the study drug and could be evaluated. The median duration of treatment was 20 weeks (range, 3-54 weeks). A dose of 1200 mg once a day was well tolerated but induced only 1 response. A DLT occurred in 3 patients treated with 600 mg twice daily, and included grade 3 fatigue, grade 3 allergic reaction, and grade 3 arthralgias; 2 responses were noted at this dose level (toxicity was graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]). Based on predetermined endpoints, the trial was closed after accrual of 15 treated patients. Assessment of biologic response for dose escalation/de-escalation decisions utilizing the apoptosis assay was not feasible.. BMS-275291 given at a dose of 600 mg twice daily induced unacceptable toxicity. The better-tolerated schedule of 1200 mg once a day demonstrated inadequate efficacy in patients with human immunodeficiency virus-associated KS. The apoptosis assay was not helpful in predicting response.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Agents; Apoptosis; CD4-Positive T-Lymphocytes; Drug Administration Schedule; Drug Evaluation; Enzyme Inhibitors; Female; Humans; Imidazoles; Male; Matrix Metalloproteinase Inhibitors; Middle Aged; Sarcoma, Kaposi; Treatment Outcome

2008