NCT00686842

PTC299 in Treating Patients With HIV-Related Kaposi Sarcoma

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

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: AIDS Malignancy Consortium · Network
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Kaposi's Sarcoma

Interventions

Type	Name	Description
DRUG	VEGF inhibitor PTC299	20 mg capsules to be taken by mouth BID. Three dose levels will be evaluated: 40 mg, 80mg, and 100mg BID. Subjects will receive PTC299 in consecutive 28-day cycles for a maximum of 12 cycles.
GENETIC	gene expression analysis	To describe the effects of PTC299 on viral gene expression and cellular gene transcription in KS tumor biopsies using real-time QPCR-based profiling.
GENETIC	polymerase chain reaction	To describe the effects of PTC299 on viral gene expression and cellular gene transcription in KS tumor biopsies using real-time QPCR-based profiling.
GENETIC	protein expression analysis	To describe the effects of PTC299 on viral gene expression and cellular gene transcription in KS tumor biopsies using real-time QPCR-based profiling.
OTHER	immunohistochemistry staining method	To describe the effects of PTC299 on KS tumor biopsies with respect to expression of VEGF, the VEGFR-2 and -3, phospho-Akt, p53, HIF-1α and proliferation, measured by Ki-67 staining.
OTHER	laboratory biomarker analysis	To describe the effects of PTC299 on KS tumor biopsies with respect to expression of VEGF, the VEGFR-2 and -3, phospho-Akt, p53, HIF-1α and proliferation, measured by Ki-67 staining.
OTHER	pharmacological study	To describe the pharmacokinetics of PTC299 in patients with HIV-associated KS. To describe the effects of PTC299 on circulating VEGF, VEGFR and cytokine levels in patients with HIV-associated KS.
PROCEDURE	biopsy	To describe the effects of PTC299 on KS tumor biopsies with respect to expression of VEGF, the VEGFR-2 and -3, phospho-Akt, p53, HIF-1α and proliferation, measured by Ki-67 staining.

Timeline

• Start date: 2008-09-01
• Primary completion: 2010-11-01
• Completion: 2010-12-01
• First posted: 2008-05-30
• Last updated: 2018-06-06
• Results posted: 2012-03-05

Locations

8 sites across 1 country: United States