ANN ARBOR — Are certain drugs more effective against some types of prostate cancers than others? Researchers know that not all therapies work for all patients. That begs the question: How do doctors match the right treatments with the right patients?
A new clinical trial is testing whether targeting treatments to a genetic anomaly can lead to better treatments for 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 phase 2 trial will look at patients with castration-resistant metastatic prostate cancer, which means the cancer has spread and has stopped responding to hormone-based treatments. The target being evaluated is a genomic rearrangement that causes two genes called TMPRSS2 and ERG to fuse together. This gene fusion, believed to be the triggering event of prostate cancer, was initially discovered in 2005 by UM researchers led by Arul Chinnaiyan, M.D.
“We hope this study will help us understand why certain patients respond to therapy and certain patients do not,” said the clinical trial’s principal investigator, Maha Hussain, M.D., professor of internal medicine and urology and associate director of clinical research at the UM Comprehensive Cancer Center. “By better understanding the evolving biology of prostate cancer, we will have the ability to better treat the disease.”
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. Each group — gene fusion positive and gene fusion negative — will then be randomly assigned so half of participants will also take an experimental drug called 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,” Hussain said.
ABT-888 is a new type of cancer-fighting drug that’s designed to block an enzyme called PARP that’s known to directly interact with the 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 tests 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 which is cancer,” Hussain said.
For information about this trial, “A Randomized Gene Fusion-Stratified Phase 2 Trial of Abiraterone with or without ABT-888 for Patients with Metastatic Castration-Resistant Prostate Cancer,” call the U-M Cancer Answerline at (800) 865-1125.
The study was funded by National Cancer Institute grant N01-CM-2011-00071C, U.S. Department of Defense grant PC080189, 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, M.D., and Arul Chinnaiyan, M.D., are co-inventors. The diagnostic field of use has been licensed to Gen-Probe Inc. Chinnaiyan also has a sponsored research agreement with Gen-Probe. Gen-Probe has no role in the design or experimentation of this study.