May 5, 2016
Enrollment into a clinical trial funded by the National Institute of Allergy and Infectious Diseases (NIAID) investigating two different strategies to treat limited-stage AIDS-related Kaposi’s sarcoma was stopped due to futility—if continued, the study would be unlikely to detect a difference between the two study arms. No safety concerns were associated with the trial.
The Phase 3, randomized, open-label trial enrolled 192 men and women in seven countries across South America and Africa since it began in November 2011. The study compared antiretroviral therapy (ART) alone or with delayed chemotherapy, to ART with immediate chemotherapy for initial treatment of limited stage AIDS-related Kaposi’s sarcoma in patients who had not previously received either chemotherapy or radiation treatment. The trial used the oral chemotherapy etoposide. If a participant’s Kaposi’s sarcoma did not improve with etoposide, additional chemotherapy treatment per the local standard of care was also permitted.
While ART initiation is recommended for all patients with HIV, including those with AIDS-related Kaposi’s sarcoma, it is not known if patients with limited AIDS-related Kaposi’s sarcoma benefit from chemotherapy, and treatment practices vary widely. Limited-stage disease often responds to ART alone, but a substantial proportion of patients with limited disease show inadequate tumor response and subsequently require chemotherapy. This trial attempted to gather data on whether chemotherapy should begin at the same time ART is started, or only after a participant experiences progression of KS disease while on ART. The oral drug etoposide was chosen for the study because it can be more easily administered than other chemotherapy agents in areas without a robust health care infrastructure.
The decision to end the trial was made following a March 10, 2016, recommendation to NIAID by the study’s data and safety monitoring board (DSMB), an independent group composed of clinical research experts, statisticians, ethicists and community representatives that meets at regular intervals throughout a study to review its safety and efficacy data. After reviewing interim data, the board concluded that the trial is unlikely to demonstrate a difference between immediate versus delayed treatment with etoposide. Many patients who received etoposide also received additional chemotherapy per the local standard of care and were thus counted as etoposide failures, making it difficult for researchers to determine the true benefit or lack of benefit from etoposide. The DSMB recommended that enrollment and randomization stop.
The study team will work with the clinical trial sites to provide the most appropriate care for participants enrolled in the clinical trial. Though the study will not continue, investigators have compiled a rich data set that will add to the scientific knowledge base on treating AIDS-related Kaposi’s sarcoma, and they have developed clinical trial infrastructure in sub-Saharan African countries that will assist future studies of HIV and cancer. Participants, site investigators, institutional review boards and regulatory agencies are being notified of the DSMB recommendations and changes to the study. The results of this study are specific for etoposide and may not apply to other chemotherapy drugs for Kaposi’s sarcoma.
The trial was conducted by the AIDS Clinical Trial Group (ACTG) with the AIDS Malignancy Consortium, and was co-funded by NIAID and the National Cancer Institute, both parts of the National Institutes of Health. The study is known as “A Randomized Evaluation of Antiretroviral Therapy Alone or with Delayed Chemotherapy versus Antiretroviral Therapy with Immediate Adjunctive Chemotherapy for Treatment of Limited Stage AIDS-KS in Resource-Limited Settings (REACT-KS)”, ACTG A5264, or AMC 067. For more information on this trial, visit ClinicalTrials.gov.