Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)

NCT01276236 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 113512860798
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this pilot study is to determine whether Maraviroc is effective in the treatment of Kaposi's Sarcoma (KS), when it does not remit with standard antiretroviral drug therapy.

Conditions

Kaposi's Sarcoma

Keywords

Kaposi's Sarcoma; Maraviroc; CCR5; HIV

Outcome Measures

Primary Outcomes (3)

• Number of Participants With a Decrease in Kaposi's Sarcoma (KS) Total Surface Area

  To assess improvements in disease, up to five bi-dimensionally measurable cutaneous KS lesions were selected as marker lesions. The collective surface area of the marker lesions was evaluated over the course of the study for either an increase or decrease in the total surface area of lesions using the modified AIDS Clinical Trials Group (ACTG) Oncology Committee Staging Criteria.

  Up to 96 weeks

• Percent Change in KS Total Surface Area

  Up to five bi-dimensionally measurable cutaneous KS lesions were selected as marker lesions and the the collective surface area of the marker lesions was evaluated over the course of the study. The percent decrease or increase in the total surface area of lesions was calculated from comparing measurements at baseline and through week 96, or at the last assessment if participant withdrew from the study prior to week 96.

  Up to 96 weeks

• Change in Edema Grade

  The presence and extent of lower extremity edema was assessed and graded on a scale from 0 to 2 in patients with a higher grade indicating a greater level of edema using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS Adverse Events (AE) Grading Table), Version 1.0. Edema grade was recorded at baseline was compared with edema grades recorded at week 96, or at last assessment if participant withdrew from study prior to week 96 and an change in grade was calculated to examine whether or not a decrease in overall grade was observed. A negative value would indicate an overall decrease in the grade of lower extremity edema, and positive value would indicate an overall increase in lower extremity edema.

  Up to 96 weeks

Secondary Outcomes (5)

• Change in Kaposi's Sarcoma-associated Herpesvirus (KSHV) Viral Load

  Up to 96 weeks

• Percent Change in CCR5 Levels on CD4+ T-Cells

  Up to 96 weeks

• Percent Change in CCR5 Levels on CD8+ T-cells

  Up to 96 weeks

• Percent Change in CD69 Expression in a Subset of Double Negative DR-CD38 Positive (DR-CD38+) T-cells

  Up to 96 weeks

• Percent Change in CD69 Expression in a Subset of Double Negative DR-CD38 Negative (DR-CD38-) T-cells

  Up to 96 weeks

Study Arms (1)

Treatment Arm (Maraviroc)

EXPERIMENTAL

The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen.

Drug: Maraviroc

Interventions

Maraviroc DRUG

FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks. Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks. Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.

Also known as: Selzentry(Celsentri outside US)

Treatment Arm (Maraviroc)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infected, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
• Active biopsy confirmed KS
• Screening plasma HIV RNA \< 75 copies/mL
• Patients have unremitting KS. Unremitting is defined as having active biopsy confirmed KS in spite of having had sustained HIV RNA \< 75 copies/mL for 24 prior months. Isolated values that are detectable but \< 500 copies will be allowed as long as the plasma HIV RNA levels before and after this time point are undetectable.
• \>90% adherence to therapy within the preceding 30 days, as determined by self-report.
• Both male and female subjects are eligible. Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period.
• Ability and willingness of subject or legal guardian/representative to provide informed consent

You may not qualify if:

• Patients who are intending to modify antiretroviral therapy in the next 24 weeks for any reason.
• Serious illness requiring hospitalization or parental antibiotics within preceding 3 months.
• Concurrent treatment with immunomodulatory drugs or therapies, or exposure to any immunomodulatory drug or therapy in past 16 weeks.
• Prior exposure to CCR5 inhibitors
• Screening absolute neutrophil count \<1,000 cells/mm3, platelet count \<50,000 cells/mm3, hemoglobin \< 8mg/dL, estimated creatinine clearance \<40 mL/minute.
• Elevated transaminases greater than 2.5 times the upper limit of normal.
• Evidence of cirrhosis
• Pregnant or breastfeeding women
• Use of both Tenofovir and Didanosine in current antiretroviral therapy regimen.
• Local therapy for any KS index lesion in preceding 60 days, unless lesion has clearly progressed with enlargement since the local therapy

Sponsors & Collaborators

• University of California, San Francisco: lead
• Pfizer: collaborator
• ViiV Healthcare: collaborator

Study Sites (1)

San Francisco General Hospital, Clinical Trials Unit

San Francisco, California, 94110, United States

Location

Related Publications (20)

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  PMID: 9287217 BACKGROUND

• Moore PS, Chang Y. Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma in patients with and those without HIV infection. N Engl J Med. 1995 May 4;332(18):1181-5. doi: 10.1056/NEJM199505043321801.

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• Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994 Dec 16;266(5192):1865-9. doi: 10.1126/science.7997879.

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• Cherqui S, Kingdon KM, Thorpe C, Kurian SM, Salomon DR. Lentiviral gene delivery of vMIP-II to transplanted endothelial cells and endothelial progenitors is proangiogenic in vivo. Mol Ther. 2007 Jul;15(7):1264-72. doi: 10.1038/sj.mt.6300183. Epub 2007 May 1.

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• Dupont C, Vasseur E, Beauchet A, Aegerter P, Berthe H, de Truchis P, Zucman D, Rouveix E, Saiag P. Long-term efficacy on Kaposi's sarcoma of highly active antiretroviral therapy in a cohort of HIV-positive patients. CISIH 92. Centre d'information et de soins de l'immunodeficience humaine. AIDS. 2000 May 26;14(8):987-93. doi: 10.1097/00002030-200005260-00010.

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• Cooley T, Henry D, Tonda M, Sun S, O'Connell M, Rackoff W. A randomized, double-blind study of pegylated liposomal doxorubicin for the treatment of AIDS-related Kaposi's sarcoma. Oncologist. 2007 Jan;12(1):114-23. doi: 10.1634/theoncologist.12-1-114.

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• Cainelli F, Vallone A. Safety and efficacy of pegylated liposomal doxorubicin in HIV-associated Kaposi's sarcoma. Biologics. 2009;3:385-90. doi: 10.2147/btt.2009.3455. Epub 2009 Sep 15.

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• Lichterfeld M, Qurishi N, Hoffmann C, Hochdorfer B, Brockmeyer NH, Arasteh K, Mauss S, Rockstroh JK; German Clinical AIDS Working Group (KAAD). Treatment of HIV-1-associated Kaposi's sarcoma with pegylated liposomal doxorubicin and HAART simultaneously induces effective tumor remission and CD4+ T cell recovery. Infection. 2005 Jun;33(3):140-7. doi: 10.1007/s15010-005-4099-z.

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• Saran FH, Adamietz IA, Thilmann C, Mose S, Bottcher HD. HIV-associated cutaneous Kaposi's sarcoma--palliative local treatment by radiotherapy. Acta Oncol. 1997;36(1):55-8. doi: 10.3109/02841869709100733.

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• McCormick SU. Intralesional vinblastine injections for the treatment of oral Kaposi's sarcoma: report of 10 patients with 2-year follow-up. J Oral Maxillofac Surg. 1996 May;54(5):583-7; discussion 588-9. doi: 10.1016/s0278-2391(96)90637-0.

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  PMID: 17898112 BACKGROUND

MeSH Terms

Conditions

Sarcoma, Kaposi

Interventions

Maraviroc

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Only 5 participants had greater than 80% cell viability in peripheral blood mononuclear cell (PBMC) specimens required for flow cytometry at baseline and final follow-up. In the remaining eight patients, either the baseline or final follow-up or both specimens had lower than 80% cell viability and were therefore excluded from immunophenotyping analyses. The small sample sizes reduced the statistical power of the reported results.

Results Point of Contact

• Title: Dr. Toby Maurer, MD
• Organization: University of California, San Francisco

Toby.Maurer@ucsf.edu

(628) 206-8680

Study Officials

• Patrick Unemori, MD

  University of California, San Francisco; San Francisco General Hospital (SFGH)

  PRINCIPAL INVESTIGATOR

• Toby Maurer, MD

  University of California, San Francisco; San Francisco General Hospital (SFGH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2010
• First Posted: January 13, 2011
• Study Start: March 9, 2011
• Primary Completion: January 31, 2015
• Study Completion: April 30, 2015
• Last Updated: March 5, 2021
• Results First Posted: March 5, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)