Clinical Trial: PTC299 in Treating Patients With HIV-Related Kaposi Sarcoma
Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional
Official Title: A Phase I/II Trial of PTC299 in Patients With HIV-Related Kaposi's Sarcoma
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 Summary:
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
Sponsor: AIDS Malignancy Consortium
Current Primary Outcome:
- Safety and Toxicity of Anti-VEGF Small Molecule PTC299 [ Time Frame: All study visits ]Patients who experienced an adverse event of grade 3 or greater
- Maximum Tolerated Dose [ Time Frame: After each group of 3 subjects completes cycle 1 of treatment ]
- Response to Treatment [ Time Frame: After each 28-day cycle of treatment and at discontinuation of therapy ]
Original Primary Outcome:
- Safety and Toxicity of Anti-VEGF Small Molecule PTC299
- Maximum Tolerated Dose
- Response rate
Current Secondary Outcome:
- Pharmacokinetics [ Time Frame: Days 1, 15, 28, 57 ]
- Effects of Study Drug on Serum and Plasma VEGF, VEGFR, and Cytokine Profiles [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Screening and day 28 ]
Original Secondary Outcome:
- Pharmacokinetics
- Effects of Study Drug on Serum and Plasma VEGF, VEGFR, and Cytokine Profiles
- Effects of Study Drug on HIV and KSHV Viral Loads
- Effects of Study Drug on T-lymphocyte Subsets (i.e., CD4 and CD8)
- 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
- 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
Information By: AIDS Malignancy Consortium
Dates:
Date Received: May 29, 2008
Date Started: September 2008
Date Completion:
Last Updated: August 27, 2014
Last Verified: August 2014