Bortezomib in Treating Patients With Relapsed or Refractory AIDS-Related Kaposi Sarcoma
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.
AIDS-related Kaposi Sarcoma
Recurrent Kaposi Sarcoma
Other: laboratory biomarker analysis
Other: questionnaire administration
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- MTD based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: 56 days ] [ Designated as safety issue: Yes ]MTD is defined as the highest assigned dose at which < 2 patients (out of 6) experience dose-limiting toxicity. Adverse events will be summarized by type, timing, and severity grade.
- Clinical KS response rates based on the Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Exact binomial 95% confidence intervals will be computed. Descriptive statistics will also be presented for complete and partial response rates.
- Changes in bortezomib in KSHV copy number in PBMC and plasma [ Time Frame: Baseline to 1 year ] [ Designated as safety issue: No ]Analyzed using the Wilcoxon signed rank test. The association between change in KSHV copy number with clinical response of KS tumors will be investigated with exact logistic regression.
- Change in lytic gene expression [ Time Frame: Baseline to 1 year ] [ Designated as safety issue: No ]The association between change in lytic gene expression with clinical response of KS tumors will be investigated with exact logistic regression. Hierarchical clustering will be used to explore if gene expression patterns differ according to clinical response.
- Changes in viral antigen expression in biopsy specimens [ Time Frame: Baseline to 1 year ] [ Designated as safety issue: No ]Spearman's rank correlations will be calculated to examine whether the changes in KSHV viral copy number in PBMC and plasma occur in concert or independently with changes in viral antigen expression in biopsy specimens collected at baseline, day 2 and treatment discontinuation.
- Changes in levels of tumor survival, proliferation proteins, and NFKappaB gene target mRNA levels [ Time Frame: Baseline to 1 year ] [ Designated as safety issue: No ]Analyzed using the Wilcoxon signed rank test.
|Study Start Date:||January 2010|
|Estimated Study Completion Date:||September 2014|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (bortezomib)
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.
Other Names:Other: laboratory biomarker analysis
Correlative studiesOther: questionnaire administration
I. Estimate the maximum tolerated dose (MTD) of single agent bortezomib in subjects with AIDS-related Kaposi sarcoma (KS).
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01016730
|United States, California|
|University of California at Los Angeles (UCLA )|
|Los Angeles, California, United States, 90095|
|University of California San Diego|
|San Diego, California, United States, 92103|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21231|
|United States, Massachusetts|
|Boston Medical Center|
|Boston, Massachusetts, United States, 02118|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Washington|
|Virginia Mason Medical Center|
|Seattle, Washington, United States, 98101|
|Principal Investigator:||Erin Reid||AIDS Associated Malignancies Clinical Trials Consortium|