Antiretroviral Therapy (ART) Alone or With Delayed Chemo Versus ART With Immediate Chemo for Limited AIDS-related Kaposi's Sarcoma

Summary

AIDS-related Kaposi's sarcoma (AIDS-KS) occurs in persons with HIV infection who are also infected with the Kaposi's sarcoma herpesvirus (KSHV). Several chemotherapy (anti-cancer) drugs work well in treating KS, but there is no treatment that cures KSHV infection. One chemotherapy drug called etoposide (VePesid®, ET) has caused KS tumors to get smaller in some people. Antiretroviral therapy (anti-HIV drugs or ART) is a group of medicines taken together to treat HIV infection. These medicines help to stop HIV from growing in the body. When this happens, the immune system, which fights infection and some cancers like KS, gets stronger. For some people, limited stage KS often improves or stays the same when they take ART. However, in some people KS continues to get worse when taking ART. These people may need chemotherapy at a later date. This study was done to find out if taking ART with immediate etoposide (ET) is better than taking ART alone or ART with delayed ET to treat limited stage KS. The study also tried to better understand KSHV and to see what kind of side effects are caused by ART and ET and how safe ART and ET are.

Timeline

Start

2011-11-18

Primary completion

2016-03-16

Completion

2018-11-29

Outcome

Missed primary endpoint

registry analysis (superiority test); Arm A: ART Alone or With Delayed ET vs Arm B: ART With Immediate ET; p = 0.911; NCT01352117 ↗

paper Failure (53.8% vs 56.6%), stable (16.3% vs 10.8%), and response (30% vs 32.5%) did not differ between arms PMID 29365083 ↗

Publications

• Background The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009).
• Background Manual for Expedited Reporting of Adverse Events to DAID, Version 2.0, January 2010. http://rsc.tech-res.com/clinical-research-sites/safety-reporting/manual
• Background Krown SE, Metroka C, Wernz JC. Kaposi's sarcoma in the acquired immune deficiency syndrome: a proposal for uniform evaluation, response, and staging criteria. AIDS Clinical Trials Group Oncology Committee. J Clin Oncol. 1989 Sep;7(9):1201-7. doi: 10.1200/JCO.1989.7.9.1201.
• Background Cianfrocca M, Cooley TP, Lee JY, Rudek MA, Scadden DT, Ratner L, Pluda JM, Figg WD, Krown SE, Dezube BJ. Matrix metalloproteinase inhibitor COL-3 in the treatment of AIDS-related Kaposi's sarcoma: a phase I AIDS malignancy consortium study. J Clin Oncol. 2002 Jan 1;20(1):153-9. doi: 10.1200/JCO.2002.20.1.153.
• Results Hosseinipour MC, Kang M, Krown SE, Bukuru A, Umbleja T, Martin JN, Orem J, Godfrey C, Hoagland B, Mwelase N, Langat D, Nyirenda M, MacRae J, Borok M, Samaneka W, Moses A, Mngqbisa R, Busakhala N, Martinez-Maza O, Ambinder R, Dittmer DP, Nokta M, Campbell TB; A5264/AMC-067 REACT-KS Team. As-Needed Vs Immediate Etoposide Chemotherapy in Combination With Antiretroviral Therapy for Mild-to-Moderate AIDS-Associated Kaposi Sarcoma in Resource-Limited Settings: A5264/AMC-067 Randomized Clinical Trial. Clin Infect Dis. 2018 Jul 2;67(2):251-260. doi: 10.1093/cid/ciy044.
• Epeldegui M, Chang D, Lee J, Magpantay LI, Borok M, Bukuru A, Busakhala N, Godfrey C, Hosseinipour MC, Kang M, Kanyama C, Langat D, Mngqibisa R, Mwelase N, Nyirenda M, Samaneka W, Hoagland B, Campbell TB, Martinez-Maza O, Krown SE; A5264/AMC-067 team. Predictive Value of Serum Biomarkers for Response of Limited-Stage AIDS-Associated Kaposi Sarcoma to Antiretroviral Therapy With or Without Concomitant Chemotherapy in Resource-Limited Settings. J Acquir Immune Defic Syndr. 2023 Oct 1;94(2):165-173. doi: 10.1097/QAI.0000000000003236.
• Kang M, Grund B, Hunsberger S, Glidden D, Volberding P. Interim monitoring in a treatment strategy trial with a composite primary endpoint. Contemp Clin Trials. 2019 Nov;86:105846. doi: 10.1016/j.cct.2019.105846. Epub 2019 Sep 11.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Etoposide	Small molecule	50 mg	Oral
Subject	Etoposide	Small molecule	100 mg	Oral
Background	efavirenz/emtricitabine/tenofovir disoproxil fumarate	Unknown	200 mg	Oral
Background	efavirenz/emtricitabine/tenofovir disoproxil fumarate	Unknown	300 mg	Oral
Background	efavirenz/emtricitabine/tenofovir disoproxil fumarate	Unknown	600 mg	Oral

Indications