PTC299 in Treating Patients With HIV-Related Kaposi Sarcoma

Phase 1

Terminated

Conditions: Kaposi's Sarcoma

Interventions: Drug: VEGF inhibitor PTC299
Genetic: gene expression analysis
Genetic: polymerase chain reaction
Genetic: protein expression analysis
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Other: pharmacological study
Procedure: biopsy

Registration Number: NCT00686842

Lead Sponsor: AIDS Malignancy Consortium

Brief 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 17

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
VEGF Inhibitor PTC299	VEGF inhibitor PTC299	Single arm study - all subjects received PTC299
VEGF Inhibitor PTC299	gene expression analysis	Single arm study - all subjects received PTC299
VEGF Inhibitor PTC299	polymerase chain reaction	Single arm study - all subjects received PTC299
VEGF Inhibitor PTC299	protein expression analysis	Single arm study - all subjects received PTC299
VEGF Inhibitor PTC299	immunohistochemistry staining method	Single arm study - all subjects received PTC299
VEGF Inhibitor PTC299	laboratory biomarker analysis	Single arm study - all subjects received PTC299
VEGF Inhibitor PTC299	pharmacological study	Single arm study - all subjects received PTC299
VEGF Inhibitor PTC299	biopsy	Single arm study - all subjects received PTC299

Primary Outcome Measures

Name	Time	Method
Response to Treatment	After each 28-day cycle of treatment and at discontinuation of therapy
Safety and Toxicity of Anti-VEGF Small Molecule PTC299	All study visits	Patients who experienced an adverse event of grade 3 or greater
Maximum Tolerated Dose	After each group of 3 subjects completes cycle 1 of treatment

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics	Days 1, 15, 28, 57
Effects of Study Drug on Serum and Plasma VEGF, VEGFR, and Cytokine Profiles	On the first day of every 28-day cycle of treatment, Day 15, and treatment discontinuation
Effects of Study Drug on HIV and KSHV Viral Loads	Screening, end of cycle 1, end of every third cycle thereafter, and treatment discontinuation
Effects of Study Drug on T-lymphocyte Subsets (i.e., CD4 and CD8)	Screening, day 29, every 3 cycles thereafter, and at treatment discontinuation
Effects of Study 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	Screening and day 28
Effects of Study Drug on Viral Gene Expression and Cellular Gene Transcription, as Measured by Real-time Quantitative PCR-based Profiling, in Tumor Biopsy Samples	Screening and day 28

Trial Locations

Locations (8): Cancer Research Center of Hawaii
🇺🇸
Honolulu, Hawaii, United States
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
🇺🇸
Columbus, Ohio, United States
USC/Norris Comprehensive Cancer Center and Hospital
🇺🇸
Los Angeles, California, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
Floyd and Delores Jones Cancer Institute at Virginia Mason Medical Center
🇺🇸
Seattle, Washington, United States
Rebecca and John Moores UCSD Cancer Center
🇺🇸
La Jolla, California, United States
UCLA Clinical AIDS Research and Education (CARE) Center
🇺🇸
Los Angeles, California, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States