A new clinical trial is testing whether targeting treatments to a genetic anomaly can lead to better treatments for castration-resistant metastatic prostate cancer. The trial, led by investigators at the University of Michigan Comprehensive Cancer Center, is being conducted at 11 sites throughout the country.
The target of this phase II trial of patients with castration-resistant metastatic prostate cancer is a genomic rearrangement that causes the genes TMPRSS2 and ERG to fuse together. This gene fusion, believed to be the triggering event of prostate cancer, was initially discovered in 2005 by U-M researchers led by Arul Chinnaiyan, MD, PhD.
“We hope this study will help us understand why certain patients respond to therapy and certain patients do not. By better understanding the evolving biology of prostate cancer, we will have the ability to better treat the disease,” said the clinical trial’s principal investigator, Maha Hussain, MD, FACP, Professor of Internal Medicine and Urology, and Associate Director of Clinical Research at the U-M Comprehensive Cancer Center.
Study Details
Study participants will undergo a biopsy to determine whether their tumor expresses the gene fusion, which occurs in about half of all prostate cancers. All participants will receive the standard hormone-based therapy abiraterone (Zytiga). Each group (gene fusion–positive and gene fusion–negative) will then be randomly assigned so that half the participants will also take the experimental drug ABT-888 in addition to abiraterone.
The trial’s design is based on scientific data indicating the potential for improving abiraterone’s effect on the tumor and that this improvement may be more evident in patients whose tumors have the gene fusion.
“Can we better select treatments for prostate cancer based on the genes in the patient’s cancer? We hope that what we learn from this study will help us to better control and better treat the deadly stage of prostate cancer,” Dr. Hussain said.
PARP Inhibitor May Play Crucial Role
ABT-888 is a PARP inhibitor that is known to directly interact with the TMPRSS2:ERG gene fusion, leading to cancer growth and progression. Lab studies have found that a PARP inhibitor, when added to hormone therapy, helped shrink tumors in general and especially those expressing the TMPRSS2:ERG gene fusion. This new clinical trial will test that finding in patients.
“In order to beat your enemy, you’ve got to understand it. We are getting closer and closer to understanding the enemy that is cancer,” Dr. Hussain added. ■
Disclosure: The study is funded by National Cancer Institute grant N01-CM-2011-00071C, U.S. Department of Defense grant PC080189, and the Prostate Cancer Foundation. The University of Michigan has received a patent on the detection of gene fusions in prostate cancer (US 7,718,369), on which faculty members Scott Tomlins, MD, PhD, and Arul Chinnaiyan, MD, PhD, are co-inventors. The diagnostic field of use has been licensed to Gen-Probe Inc. Dr. Chinnaiyan also has a sponsored research agreement with Gen-Probe. Gen-Probe has no role in the design or experimentation of this study.
