Investigating Chemotherapy Treatments, Response and Subsets of HIV-associated Kaposi Sarcoma in Malawi

The purpose of this study is to identify important associations between complete and comprehensive clinical, laboratory, and genomic data derived from patients and tumor specimens, with prospectively recorded clinical outcomes. The investigators also hope to move beyond simple risk factor associations as previously described, to develop a composite score specifically for KS recurrence or progression, analogous to widely used risk scores that are used to direct up-front treatment of other cancers. In so doing, the investigators will draw on extremely granular data to prospectively identify patients who are most likely to benefit from new treatments.

Study Overview

• Status: Completed
• Conditions: HIV; Kaposi Sarcoma

Detailed Description

This is a prospective, nonrandomized, open-label, single arm, cohort study of pathologically confirmed HIV-associated KS patients initiating chemotherapy in Malawi. The primary objective of this study is to estimate the complete response rate (CR by ACTG criteria) at 48 weeks. This will be done both overall and by chemotherapy (BV or not BV) treatment group. Secondary objectives are to estimate PFS and OS for both overall and by chemotherapy treatment group. Exploratory objectives include the investigation of: select clinical variables and laboratory biomarkers among HIV-associated KS patients and their possible association with response, PFS, and OS; the histopathology of KSHV-associated lymphoproliferative diseases among HIV-associated KS patients; KSHV strains in tumor biopsies, PBMC and plasma, and KSHV gene expression characteristics between KS that develops on and off ART.

The investigators plan to accrue 200 HIV-associated KS patients at a rate of approximately 50 patients per year. Approximately half of the patients will receive BV chemotherapy treatment. An important factor for this study's size is that it will be comparable to or exceed the size of other important KS cohort studies, which have demonstrated significant differences in outcomes based on gender or baseline KSHV DNA levels.

The investigators want to show that there are definable biologic and clinical subsets within the HIV-associated KS population, and that identifying these subsets will have direct relevance to more effective treatment strategies for these patients.

• Study Type: Observational
• Enrollment (Actual): 157

Contacts and Locations

Study Locations

• Malawi
  • Lilongwe, Malawi
    • UNC Project
  • Lilongwe, Malawi
    • UNC Project, Lighthouse Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

HIV-infected adults ≥18 years of age with pathologically confirmed KS who are initiating chemotherapy at Lighthouse Trust or the KCH Cancer Clinic.

Description

Inclusion Criteria:

• Histologically confirmed KS initiating chemotherapy at Lighthouse Trust or the Kamuzu Central Hospital (KCH) Cancer Clinic
• HIV positive (confirmed at any time point prior by local standard of care assay) on or off ART
• Age ≥18 years
• Residence <200 kilometers from KCH
• Able to understand and comply with study procedures for the entire length of the study
• Subject able to understand and provide written consent in English or Chichewa Informed consent reviewed and signed by patient

Exclusion Criteria:

• Failure to meet inclusion criteria listed above.
• Specifically, pregnancy and breastfeeding are not exclusion criteria given the observational nature of the study with diagnostic and treatment interventions administered according to local standards of care.
• KS relapse disease as defined by a prior KS diagnosis within 1 year prior to enrollment.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimate the complete response rate (CR) at 48 weeks of HIV-associated KS patients overall and by BV treatment group.	the assessment of a patient's response (CR) to chemotherapy at 48 weeks by ACTG criteria	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimate the Progression Free Survival (PFS) in HIV-associated KS patients overall and by bleomycin-vincristine (BV) treatment group	PFS which will be defined as the time from treatment initiation until disease progression or death	48 weeks
Estimate OS in HIV-associated KS patients overall and by BV treatment group	To estimate OS in HIV-associated KS patients overall and by BV treatment group	48 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The clinical variables and laboratory biomarkers among HIV-associated KS patients and their possible association with response, PFS, and OS	The prevalence and nature of lymphoproliferative diseases among HIV-associated KS patients	48 weeks
The histopathology of KSHV-associated lymphoproliferative diseases among HIV-associated KS patients	KSHV gene expression characteristics for HIV-associated KS that develops on and off antiretroviral therapy (ART)	48 weeks
The kind of KSHV strains in tumor biopsies, PBMC and plasma	Viral genome features of HIV-associated KS	48 weeks
The KSHV gene expression characteristics between KS that develops on and off ART	To describe KSHV gene expression characteristics between KS that develops on and off ART	48 weeks

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Dirk Dittmer, UNC-CH

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): October 1, 2020
• Study Completion (Actual): October 1, 2020

Study Registration Dates

• First Submitted: May 2, 2017
• First Submitted That Met QC Criteria: May 17, 2017
• First Posted (Actual): May 19, 2017

Study Record Updates

• Last Update Posted (Actual): December 17, 2020
• Last Update Submitted That Met QC Criteria: December 15, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: initiating chemotherapy; prospective, open label, single arm, cohort; non randomized, non interventional
• Additional Relevant MeSH Terms: Virus Diseases; Infections; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; DNA Virus Infections; Herpesviridae Infections; Neoplasms, Vascular Tissue; Sarcoma; Sarcoma, Kaposi
• Other Study ID Numbers: LCCC 1424

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED