A Phase I/II Trial of PTC299 in Patients With HIV-Related Kaposi's Sarcoma
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.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety and Toxicity of Anti-VEGF Small Molecule PTC299
Patients who experienced an adverse event of grade 3 or greater
All study visits
Yes
Susan E. Krown, MD
Study Chair
Memorial Sloan-Kettering Cancer Center
United States: Federal Government
CDR0000596565
NCT00686842
September 2008
December 2010
Name | Location |
---|---|
Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
Beth Israel Deaconess Medical Center | Boston, Massachusetts 02215 |
Cancer Research Center of Hawaii | Honolulu, Hawaii 96813 |
USC/Norris Comprehensive Cancer Center and Hospital | Los Angeles, California 90033-0804 |
Rebecca and John Moores UCSD Cancer Center | La Jolla, California 92093-0658 |
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center | Columbus, Ohio 43210-1240 |
UCLA Clinical AIDS Research and Education (CARE) Center | Los Angeles, California 90024 |
Floyd and Delores Jones Cancer Institute at Virginia Mason Medical Center | Seattle, Washington 98111 |