PTC299 in Treating Patients With HIV-Related Kaposi Sarcoma

Kaposi's Sarcoma Clinical Trial

Official title: A Phase I/II Trial of PTC299 in Patients With HIV-Related Kaposi's Sarcoma

Status Terminated

Clinical Trial Summary

RATIONALE: PTC299 may stop the growth of Kaposi sarcoma by blocking blood flow to the tumor.

PURPOSE: This phase I/II trial is studying the side effects and best dose of PTC299 and to see how well it works in treating patients with HIV-related Kaposi sarcoma.

Clinical Trial Description

OBJECTIVES:

Primary

• To define the safety and toxicity of anti-VEGF small molecule PTC299 in patients with HIV-related Kaposi sarcoma.

• To establish the maximum tolerated dose of this drug in these patients.

• To estimate the response rate in patients treated with this drug.

Secondary

• To describe the pharmacokinetics of this drug in these patients.

• To describe the effects of this drug on serum and plasma VEGF, VEGFR, and cytokine profiles in these patients.

• To describe the effects of this drug on HIV and KSHV viral loads in these patients.

• To describe the effects of this drug on T-lymphocyte subsets (i.e., CD4 and CD8) in these patients.

• To describe the effects of this drug on VEGF, VEGFR-2 and -3, phospho-Akt, p53, and HIF-1α expression and tumor cell proliferation, as measured by Ki-67 staining, in tumor biopsy samples obtained from these patients.

• To describe the effects of this drug on viral gene expression and cellular gene transcription, as measured by real-time quantitative PCR-based profiling, in tumor biopsy samples obtained from these patients.

OUTLINE: This is a multicenter, phase I dose-escalation study of anti-VEGF small molecule PTC299 followed by a phase II study.

Patients receive oral anti-VEGF small molecule PTC299 twice daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients who do not demonstrate an objective response of their Kaposi sarcoma (KS) lesions after 6 courses of treatment are removed from the study.

Patients undergo blood sample collection and punch biopsies periodically during study for correlative laboratory studies. Biopsy samples are assessed for VEGF, VEGFR-2, VEGFR-3, phospho-Akt, KSHV LANA, orf59, p53, and HIF-1α expression by IHC; tumor cell proliferation by Ki-67 staining; and viral gene expression at the messenger RNA level and KSHV transcription by real-time quantitative PCR-based profiling. Blood samples are assessed for pharmacokinetics and levels of secreted cytokines or other potential serum markers characteristic for KS.

After completion of study treatment, patients are followed at 30 days. ;

Related Conditions & MeSH terms

• Kaposi's Sarcoma
• Sarcoma
• Sarcoma, Kaposi

• NCT number: NCT00686842
• Study type: Interventional
• Source: AIDS Malignancy Consortium
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: September 2008
• Completion date: December 2010