Bortezomib in Treating Patients With Relapsed or Refractory AIDS-Related Kaposi Sarcoma
|ClinicalTrials.gov Identifier: NCT01016730|
Recruitment Status : Completed
First Posted : November 19, 2009
Last Update Posted : February 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|AIDS-Related Kaposi Sarcoma HIV Infection Recurrent Kaposi Sarcoma||Drug: Bortezomib Other: Laboratory Biomarker Analysis Other: Questionnaire Administration||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||January 22, 2010|
|Actual Primary Completion Date :||January 7, 2015|
|Actual Study Completion Date :||January 7, 2015|
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: Laboratory Biomarker Analysis
Other: Questionnaire Administration
- MTD based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: 56 days ]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.
- Change in lytic gene expression [ Time Frame: Baseline to 1 year ]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 bortezomib in KSHV copy number in PBMC and plasma [ Time Frame: Baseline to 1 year ]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.
- Changes in levels of tumor survival, proliferation proteins, and NFKappaB gene target mRNA levels [ Time Frame: Baseline to 1 year ]Analyzed using the Wilcoxon signed rank test.
- Changes in viral antigen expression in biopsy specimens [ Time Frame: Baseline to 1 year ]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.
- Clinical KS response rates based on the Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 1 year ]Exact binomial 95% confidence intervals will be computed. Descriptive statistics will also be presented for complete and partial response rates.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01016730
|United States, California|
|UC San Diego Moores Cancer Center|
|La Jolla, California, United States, 92093|
|UCLA Center for Clinical AIDS Research and Education|
|Los Angeles, California, United States, 90035|
|UCLA / Jonsson Comprehensive Cancer Center|
|Los Angeles, California, United States, 90095|
|University of California San Diego|
|San Diego, California, United States, 92103|
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|United States, Massachusetts|
|Boston Medical Center|
|Boston, Massachusetts, United States, 02118|
|United States, New York|
|Memorial Sloan Kettering-Rockefeller Outpatient Pavilion|
|New York, New York, United States, 10022|
|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 Malignancy Consortium|