Single-Arm, Dose-Finding Pilot Trial of Single-Agent Bortezomib in Patients With Relapsed/Refractory AIDS-Associated Kaposi Sarcoma With Correlative Assessments of KSHV and HIV
I. Estimate the MTD of single agent bortezomib in subjects with AIDS-related KS.
I. Evaluate the clinical response of KS tumors to bortezomib. II. Evaluate the impact of
bortezomib on HIV plasma viral loads and peripheral blood mononuclear cells (PBMC) APOBEC3G
III.Determine the impact of bortezomib on KSHV. IV. Assess bortezomib effects on KSHV copy
number in PBMC and plasma and whether changes in viral copy number measured in PBMC and
plasma are associated with clinical response of KS tumors.
V. Monitor KSHV gene expression in KS biopsy specimens and PBMC pre- and post-bortezomib and
assess whether changes in viral gene expression (i.e., to a lytic pattern) in tumor biopsy
are associated with clinical response.
VI. Assess whether changes in viral copy number in PBMC and plasma occur in concert with or
independently of changes in viral antigen expression in tumor biopsy specimens.
VII. Assess effects of bortezomib on proteins relevant to KS tumor survival and
proliferation (i.e., P53, VHL, p27, HIF1-alpha) as well as levels of NFkappaB gene target
mRNAs in tumor biopsies.
OUTLINE: This is a multicenter study.
Patients receive bortezomib IV on days 1, 8, and 15. Treatment repeats every 28 days for up
to 8 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo blood and tumor tissue sample collection periodically for correlative
biomarker studies, including measurement of KSHV viral loads, gene expression analysis,
measurement of APOBEC3G levels by IHC, and RNA analysis by reverse transcriptase-PCR.
After completion of study treatment, patients are followed up at 4 weeks and then every 3
months for up to 1 year.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Up to 28 days
AIDS Associated Malignancies Clinical Trials Consortium
United States: Food and Drug Administration
|AIDS - Associated Malignancies Clinical Trials Consortium||Rockville, Maryland 20850|