Metastatic Prostate Cancer Clinical Study

A new clinical trial offered at the University of Michigan Comprehensive Cancer Center and 10 other sites throughout the country is testing whether targeting treatments to a genetic anomaly -- or gene fusion -- can lead to better treatments for prostate cancer.

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 U-M researchers.

Here are some answers to frequently asked questions about this trial. To learn more, contact the U-M Cancer AnswerLine™ at 800-865-1125.

What is the title of 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. Read the complete protocol.

What phase is this study and what does that mean?

This is a phase 2 trial. Clinical studies are divided into phases 0-4. Phase 2 studies gather preliminary data on whether the drug works in a specific cancer and look at safety and side effects. Who qualifies for this study? Men with metastatic castration-resistant prostate cancer, that is, prostate cancer that is progressing on hormone therapy (medical or surgical castration), may be eligible for this study. To participate, you must not have started therapy with abiraterone (Zytiga) and you must agree to undergo a biopsy of at least one metastatic site. You may not be receiving any other investigational drugs and must complete any chemotherapy or radiation therapy at least three weeks prior to starting the study.

There are additional eligibility requirements. To learn more, call the U-M Cancer AnswerLine™ at 800-865-1125.

What does it mean for prostate cancer to be "castration resistant"?

Treatments for prostate cancer typically include either drugs to suppress testosterone production from the testes or surgical removal of the testes. Testosterone is a male hormone that controls the normal growth of the prostate and growth of prostate cancer. This treatment typically works at first, but over time the cancer cells become resistant to the therapy and the cancer returns.

What does it mean for cancer to be metastatic?

Metastatic cancer is cancer that has spread from the place where it first started (the prostate) to another place in the body (bone, lymph node, liver, lung).

Why is a biopsy necessary?

A biopsy will allow researchers to determine whether your tumor expresses a specific genetic anomaly that is being studied.

What is this genetic anomaly?

Researchers at the University of Michigan discovered a unique occurrence of two genes fusing together which may be what triggers prostate cancer. This gene fusion is present in about half of all prostate cancers and can be detected by evaluating tissue from the tumor.

What is the goal of this study?

This study has 2 goals:

1. To determine if we can improve on current therapy with abiraterone by adding an experimental agent, ABT-888, that impairs the cancer cells' abilities to repair themselves

2. To determine whether men whose tumors have this gene fusion will experience better outcome with either treatments. Patients will be randomly assigned to get the standard therapy abiraterone alone or with the experimental drug ABT-888.

If patients with the gene fusion have a better response, it would allow doctors to better target this treatment to patients with the gene fusion. That would ensure the best result in that group of patients and would spare patients whose tumor is gene fusion negative from a treatment that is not likely to be effective.

A secondary question includes looking at what other genetic markers are present that could potentially be targeted with other treatments.

What treatment will I receive? Can I choose?

Study participants will be grouped based on whether their tumor has the gene fusion. Among each group - gene fusion positive and gene fusion negative - participants will be randomly assigned to receive the standard therapy abiraterone or abiraterone plus the experimental drug ABT-888. In order to ensure the scientific integrity of the study, study participants cannot choose their treatment.

The study protocol involves taking 4 250-mg tablets of abiraterone once per day by mouth and 5 mg of prednisone twice per day by mouth. This is standard therapy. Participants receiving ABT-888 will also take one 300-mg capsule twice a day by mouth. Treatment continues until the cancer progresses or until you choose to discontinue. Patients may choose to stop their participation in the study at any time for any reason.

What is abiraterone?

Abiraterone (Zytiga) is a pill that is FDA-approved and is standard therapy for men with this type of prostate cancer.

What do scientists know about this gene fusion?

In 2005, researchers led by Arul Chinnaiyan found that a prostate-specific gene called TMPRSS2 fuses with a cancer-causing gene called ERG. They showed that this gene fusion, which occurs in about half of all prostate cancers, acts as an "on switch" to trigger prostate cancer. Researchers believe that targeting treatments the gene fusion is the key to better treatments and better outcomes. Laboratory research has also shown that the gene fusion is fueled by the hormone androgen. Because abiraterone targets androgen, researchers suspect that the drug may have more impact in patients with the gene fusion.

What is known about the experimental drug ABT-888?
What is the basis for looking at ABT-888 for prostate cancer?

ABT-888 is a type of drug called a PARP inhibitor. PARP is an enzyme that regulates certain cell functions. Laboratory research suggests that PARP is active in castration-resistant prostate cancer, fueling the tumor to grow and spread. Blocking PARP can halt that process. This study will test that theory in patients.

Has ABT-888 been given to patients before?

ABT-888 is not FDA approved but it has been tested in other clinical trials.

Where is this study being conducted?

The University of Michigan Comprehensive Cancer Center is one of 11 locations offering this trial. Other locations are:

  • Cancer Institute of New Jersey
  • City of Hope Cancer Center
  • Indiana University
  • Johns Hopkins University
  • MD Anderson Cancer Center
  • University of Chicago
  • University of North Carolina at Chapel Hill
  • University of Southern California
  • University of Washington
  • University of Wisconsin

Where can I learn more about clinical trials?

View our complete Introduction to Clinical Trials and learn what it means to participate. Talk to a nurse - call the U-M Cancer AnswerLine™ at 800-865-1125.

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