The Radiation Therapy Oncology Group (RTOG) study is the first phase III randomized trial to examine the combination of orteronel [TAK-700] with standard androgen deprivation therapy and concurrent radiation.
Over 28,000 men in the United States are projected to die of prostate cancer this year. Up to 10% of men with newly diagnosed prostate cancer have advanced disease and are at high risk for reoccurrence and spread of their cancer. Currently, standard treatment for high-risk locally advanced prostate cancer is a combination of radiation therapy and androgen deprivation therapy (ADT) such as with a GnRH agonist to suppress testosterone production which can fuel the cancer’s growth.
M. Dror Michaelson, MD, PhD of Massachusetts General Hospital and the RTOG 1115 trial’s principal investigator explains that high-risk prostate cancer is frequently not effectively treated with this regimen, “Primary [or standard] hormone therapy aims to reduce testosterone levels in men by stopping testicular production of testosterone. While this eradicates the body’s main source of testosterone, some still is produced in the adrenal glands and in the cancer itself. Orteronel [TAK-700] appears to stop all testosterone production in the body.”
Standard treatment has been shown to reduce testosterone levels in high-risk patients by up to 95%. In phase I and phase II trials, orteronel has been shown to amplify these results. The RTOG 1115 trial seeks to determine if the addition of orteronel to standard treatment significantly extends high-risk patients’ lives. If so, “Orteronel can quickly be adopted into clinical care, increasing the cure rate of men with high-risk prostate cancer,” says Michaelson.
The side effects associated with standard ADT treatment are well known and vary from fatigue to hot flashes to loss of libido. Assessing the addition of orteronel on study participants’ quality of life is another important study component. “While we anticipate orteronel will improve survival, we also need to assess this treatment’s impact on quality of life. It is important to balance improvement in survival with decreases in quality of life; survival is always our number one concern, but we are also concerned with the quality of that survival,” says Deborah Bruner, RN, PhD, FAAN of Nell Hodgson Woodruff School of Nursing and Winship Cancer Institute of Emory University and the trial’s outcomes co-chair.
“In this study, we are carefully monitoring the symptoms of androgen deprivation therapy. Additionally, we are looking at the biological pathways by which ADT treatment causes these symptoms. We know that men who receive radiation and ADT have increased fatigue, but why? What is the pathway? This is important to discover so we can find targeted agents to interrupt the pathway and prevent the fatigue.”
“This trial has the potential to improve outcomes for a significant population of patients with prostate cancer. The trial’s quality of life biomarker investigation is expected to help us better understand the etiology of fatigue and treatment side effects for individual patients,” says Walter J. Curran, Jr., MD, RTOG Group Chair and Executive Director of the Winship Cancer Institute of Emory University in Atlanta.
Approximately 900 participants with high-risk prostate cancer will participate. Participants will be randomized by computer program into one of two treatment arms: participants randomized into arm 1 will receive standard radiation therapy and hormone therapy for 24 months. Participants in arm 2 will receive the same standard treatment and will also take Otoronel in pill form two times a day for 24 months.
For more information, including detailed qualifications for high-risk classification, go to: http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=1115