PHII-123, NCI 9012: A Randomized Gene Fusion Stratified Phase 2 Trial of Abiraterone with or without ABT-888 for Patients with Metastatic Castration-Resistant Prostate Cancer

SUMMARY

You have been asked to participate in this research study because you have prostate cancer. The purpose of this study is to look at the role of a specific gene hybrid formed from two previously separate genes (known as ETS gene fusion) to see if it can predict response to abiraterone (a hormone therapy) with prednisone or abiraterone with prednisone plus the experimental drug ABT-888 in patients with metastatic (cancer that has spread throughout the body) castration resistant prostate cancer.  The researchers in this study will also look at whether the addition of ABT-888 to abiraterone with prednisone is better when compared to abiraterone and prednisone without ABT-888.   Your treatment on this study is expected to last as long as your cancer is responding to the study drug regime.  The study drug regime could be stopped for reasons such as unacceptable side effects or you decide to no longer take part in the study. 

After your treatment on this study is over, your medical condition will continue to be followed indefinitely.

Every year in the United States there are more than 200,000 new cases and almost 30 thousand deaths from prostate cancer. Patients in whom prostate cancer had spread throughout the body are treated with therapies that lower testosterone hormone level (usually referred to as hormone therapy or castration therapy). This is initially very effective but after a period of time (usually 1.5-2 years) cancer develops resistance and begins to grow again despite castration therapy (castration resistant prostate cancer). There are many therapies utilized in that situation including immunotherapy (to stimulate patient’s immune system to fight cancer), chemotherapy, radiation therapy and new generation of hormonal agents.

Abiraterone is one of the new hormonal agents that works by suppressing the production of testosterone more completely than standard castration therapy. Abiraterone is not equally effective in all patients with prostate cancer and eventually cancer also develops resistant to that agent. There is data indicating that the response to abiraterone may be stronger in patients who have prostate cancer that harbors a specific gene abnormality called ETS fusion gene. This abnormality is present in about 50% of prostate cancers. There is also evidence suggestive that drugs from the class called PARP inhibitors (PARP is a molecule involved in the normal repair of genetic material DNA) can enhance the activity of abiraterone. This study will attempt to determine if indeed the patients who have cancer with ETS mutation/fusion gene have a better response to abiraterone and if the addition of PARP inhibitor agent ABT-888 enhances the effectiveness of abiraterone. These are very important questions to answer and eventually may allow the physicians to predict in advance if the patient will respond well to treatment with abiraterone and if PARP inhibitor improves the effectiveness of abiraterone.        

Abiraterone with prednisone is approved by the United States Food and Drug Administration (FDA) for use in the treatment of metastatic castration resistant prostate cancer.  ABT-888 is an experimental drug that has not been approved by the FDA.    

COH Protocol Number : 12284

ClinicalTrials.gov Number : NCT01576172

Principal Investigator : Twardowski, Przemyslaw M.D.

Sponsor : California Cancer Consortium (CCCP)-University of Chicago

BRIEF ELIGIBILITY CRITERIA :

Eligible Ages : >=18

Gender : Male

Treatment Intent : Adjuvant treatment

Prior Chemotherapy :

Brain Metastases :

Measurable Disease :