Abiraterone trial to launch in early stage prostate cancer
A highly anticipated new androgen synthesis inhibitor, abiraterone acetate, will be the subject of the first clinical study in men with localized, but high-risk, prostate cancer. Led by DF/HCC researcher Mary-Ellen Taplin, MD (DFCI), the study will include two androgen inhibitors—abiraterone plus leuprolide acetate – intended to block androgen synthesis more completely in patients with early stage prostate cancer prior to prostatectomy. Though participants in the study have localized prostate cancer, they are still considered high-risk because they either have a high Gleason score (>8), elevated PSA (>20 ng/mL), or their disease appears to be Stage T3 in the capsule or seminal vesicle(s).
Objective and importance of this trial
Men with high-risk prostate cancer have the traditional treatment options of surgery (prostatectomy) or radiation and androgen deprivation therapy (hormone therapy). Unfortunately, due to the aggressive nature of high-risk prostate cancers the relapse rates following these treatments are high. Standard hormone therapy with compounds that inhibit production of testosterone from the testicles has been evaluated prior to prostatectomy and it did not yield higher clinical benefits.
In men, testosterone is produced in the adrenal glands in addition to the testicles. Recently, it has been discovered that prostate cancer cells themselves can produce testosterone that stimulates cancer growth without depending on testosterone in the blood stream. Investigators hypothesize that a more “powerful” form of hormone therapy that suppresses testosterone production from not only the testicles but also the adrenals and the prostate cancer cells would result in greater cancer kill.
“We think abiraterone can reduce testosterone synthesis within the prostate cell,” explains Taplin. “It is a more comprehensive androgen suppressor.” The major aim of this study is to determine exactly that by measuring the intracellular levels of testosterone from the prostates of men treated with abiraterone compared to standard leuprolide.
Abiraterone is a first in class orally available, small molecule drug that inhibits the activity of two key enzymes involved in testosterone synthesis: C17, 20-lyase and 17α hydroxylase. “This drug is suppressing testosterone synthesis everywhere – the testicles, the adrenals, the cancer cells,” says Taplin. It has been shown to reduce testosterone in the blood to levels never seen before—less than 1 ng/mL whereas standard ways of reducing testosterone, such as leuprolide, only suppress to levels of 20-50 ng/mL.
This Phase II study has a recruitment goal of 58 patients. One arm of the study (29 participants) will receive leuprolide therapy alone for three months. The other will be given leuprolide and a daily 1 gm oral dose of abiraterone acetate. Patients will receive three months of hormone therapy, then have a standard prostate biopsy to measure the levels of testosterone within the prostate and prostate cancer cells. All study participants will then receive an additional three months of combined leuprolide and abiraterone followed by prostatectomy.
“We will evaluate the prostate pathology specimens to determine if in any cases this combination of hormone therapy was able to kill all the prostate cancer cells prior to prostate removal,” explains Taplin. If investigators find any complete remissions in the prostate glands, the approach will be considered for a larger clinical trial.
“This will be the first group of patients to get this drug in the early stage, hormone-naïve setting,” explains Taplin. Two Phase III studies with abiraterone involved patients with late stage, metastatic disease. Says Taplin, “We have high hopes for this approach. Everyone in the country who does this type of work knows about this trial and is excited and interested to see the results.” The study is supported by a grant from the Prostate Cancer Foundation and by Johnson and Johnson.
A Phase 2 Open-Label, Randomized, Multi-center Study of Neoadjuvant Abiraterone Acetate (CB7630) Plus Leuprolide Acetate and Prednisone Versus Leuprolide Acetate Alone in Men With Localized High Risk Prostate Cancer
Mary-Ellen Taplin, MD (DFCI)
For eligibility criteria, contact information, and sites, go to NCT00924469 on ClinicalTrials.gov