According to information released earlier today by Tokai Pharmaceuticals, the company has started to enroll patients with AR-V7-positive, metastatic, castration-resistant prostate cancer (mCRPC) into a randomized Phase III clinical trial of treatment with galeterone.
In addition, the Tokai media release states that, in combination with their business partner Qiagen, global deployment of a new assay to test men for risk of the AR-V7 mutation has now been initiated.
The so-called ARMOR3-SV trial has been designed to enroll about 150 patients with AR-V7 mCRPC who have progressive metastatic (M1) disease on androgen deprivation therapy (ADT), detectable AR-V7 from circulating tumor cells (CTCs), and an ECOG performance status 0 or 1. Patients can not, however, have received any prior treatment with a second generation anti-androgen (e.g. abiraterone actetate/Zytiga or enzalutamide/Xtandi) or with any form of chemotherapy.
Patients will be randomized to treatment with either galeterone (2,250 mg once daily) or enzalutamide (160 mg once daily). The primary endpoint will be radiographic progression-free survival (RPFS). Secondary endpoints will include overall survival and time to initation of cyctotoxic chemotherapy. ARMOR3-SV has been initiated at more than 15 sites in the USA. Sites in Canada and the UK are anticipated later this month. Additional study centers throughout North America, Western Europe, and Australia are expected in the near future.
The company states that they expect to be able to obtain initial results of this trial within less than 2 years.
Filed under: Diagnosis, Drugs in development, Living with Prostate Cancer, Management, Risk, Treatment | Tagged: AR-V7, castration-resistant, galeterone, mCRPC, metastatic |
THE "NEW" PROSTATE CANCER INFOLINK 
Unfortunately Tokai is being too exclusive with this. There are plenty of men that are probably AR-V7 positive but when you exclude those men who have not had abiraterone, enzalutamide, or chemotherapy, it really limits the size of the candidate pool.
We need a trial of galeterone in men who have tried and failed abiraterone and/or enzalutamide! Earlier published results from a very small trial reported earlier were promising … men in that category with very limited treatment options need help sooner rather than later.
So pleased to learn that Tokai has brought galeterone to trial. We have learned of the effect of AR-V7 and that men can be tested for its presence before beginning Zytiga/abiraterone acetate or Xtandi/enzalutamide, but have awaited the availability of galeterone should men be found with the presence of AR-V7 splice variant androgen receptor. We would hope that with early success the medication comes available sooner than the 2 years remarked. In the meantime, testing for the presence of AR-V7 is expected to be available either by Qiagen or by the Johns Hopkins CLIA laboratory by August or September.
While I completely understand the desire/need to demonstrate whether galeterone is effective and safe in men who have already progressed on abiraterone and/or enzalutamide and/or chemotherapy, in defense of Tokai, I believe that the company has sought a path to bring galeterone to market in the shortest time possible. They (and I) appear to believe that by carrying out the Phase III trial using the design outlined above and in the summary of the protocol on the ClinicalTrials.gov link given, they are more likely to be able to prove efficacy faster and by using a far smaller number of patients than if they were to do a trial that included men who have already progressed on abiratrone and/or enzalutamide and/or chemotherapy (which would almost certainly require a much higher number of patients that would take much longer to enroll).
If one looks at this trial from that perspective, and they are able to prove that galeterone is effective in the treatment of at least a subset of men with early AR-V7-positive disease, then the drug would at least be available as quickly as possible for use in the treatment of all men with AR-V7-positive disease.
If successful it won’t be approved for this usage for at least another 18 months unless by some freak chance it gets fast tracked. If we look at Xtandi it took what 3-4 yrs before it was made available for pre-chemo castration-resistant men? So you can figure it could be almost 5 years before men who have failed prior treatments have a chance at this drug. We are running out of options.
I would be interested in taking part and believe I qualify on all counts. I am about to start on a second-generation anti-androgen — but don’t know which one because I am concerned at the possibility of being AR-V7 positive — no way of telling.
But how does a Brit become a participant?
Any advice?
Graham
Graham:
My bet would be that if they start doing trials in the UK in the next couple of months (which is what it said in the media release), one of the first places that they will be enrolling patients in the UK would be at the Royal Marsden Hospital. You might want to contact them and tell them that you are interested.
Dominic:
It is perfectly possible — and not unreasonable — that if this trial is successful, the indication that is given to galeterone by the FDA would be “For treatment of men with AR-V7-positive, metastatic, castration-resistant prostate cancer” … with no mention of whether patients had or had not received abiraterone, enzalutamide, or chemotherapy. For obvious reasons, the “other way around” (i.e., the pathway followed by abiraterone and by enzalutamide) doesn’t work, but if the drug works in the proposed setting, there is no necessary reason to believe it wouldn’t work in later settings, and your doctor could certainly prescribe it anyway.
Sitemaster, to your reply to Dom …
As is usual to prescribing drugs in unconfirmed settings is the payer problem. And while we do not know costs yet, we can expect it to be restricted to FDA confirmed settings if the cost is exorbitant. But we have a ways to go to find out.
Tony:
Yes. I appreciate that. My point is that until we know what the FDA-approved indication for the drug might be, all of this is speculation.