NCT01016730

Bortezomib in Treating Patients With Relapsed or Refractory AIDS-Related Kaposi Sarcoma

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This pilot, phase I trial studies the side effects and best dose of bortezomib in treating patients with acquired immune deficiency syndrome (AIDS)-related Kaposi sarcoma that has come back or has not responded to treatment. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. Estimate the maximum tolerated dose (MTD) of single agent bortezomib in subjects with AIDS-related Kaposi sarcoma (KS). SECONDARY OBJECTIVES: I. Evaluate the clinical response of KS tumors to bortezomib. II. Evaluate the impact of bortezomib on human immunodeficiency virus (HIV) plasma viral loads and peripheral blood mononuclear cells (PBMC) apolipoprotein B messenger ribonucleic acid (mRNA) editing enzyme, catalytic polypeptide-like 3G (APOBEC3G) levels. III. Determine the impact of bortezomib on Kaposi's sarcoma-associated herpesvirus (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, von Hippel-Lindau \[VHL\], p27, hypoxia-inducible factor 1 \[HIF1\]-alpha) as well as levels of nuclear factor-kappaB (NFkappaB) gene target mRNAs in tumor biopsies. OUTLINE: This is a dose-escalation study. Patients receive bortezomib intravenously (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. After completion of study treatment, patients are followed up at 4 weeks and then every 3 months for up to 1 year.

Conditions

• AIDS-Related Kaposi Sarcoma
• HIV Infection
• Recurrent Kaposi Sarcoma

Interventions

Type	Name	Description
DRUG	Bortezomib	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Questionnaire Administration	Ancillary studies

Timeline

• Start date: 2010-01-22
• Primary completion: 2015-01-07
• Completion: 2015-01-07
• First posted: 2009-11-19
• Last updated: 2018-02-20

Locations

9 sites across 1 country: United States