Posted on April 11, 2018 by Sitemaster
According to a recent media release, a company called Endocyte has reached agreement with the US Food and Drug Administration about the design of a pivotal Phase III clinical trial that will test the effectiveness and safety of 177Lu-PSMA-617 in men with recurrent, metastatic, castration-resistant prostate cancer (mCRPC).
The media release, which was actually issued in February, says that this trial will be known as the VISION trial., and it will be an international, prospective, open-label, multi-center, randomized study that enrolls patients who have already been treated with and progressed after treatment with
- Standard androgen deprivation therapy (ADT) and
- At least one “novel androgen axis drug” or NAAD (e.g., abiraterone acetate or enzalutamide) and
- At least one taxane regimen (e.g., docetaxel or cabazitaxel)
The trial will enroll up to 750 patients who test positive on PSMA scans (probably a gallium-67 PSMA scan, although the media release does not actually say that.
Eligible patients will then be randomized in a 2:1 manner to treatment with
- Either 177Lu-PSMA-617 and best supportive care alone or best supportive care with an NAAD of the physician’s choice (Arm A)
- Or best supportive care alone or best supportive care with an NAAD of the physician’s choice (Arm B)
This means that there will be roughly 500 men in Arm A of the trial and roughly 250 in Arm B.
The patients who are treated with the lutetium-177 will receive doses of 7.4 GBq of 177Lu-PSMA-617 every 6 weeks for a maximum of six cycles.
The primary study endpoint will be overall survival (OS). Secondary endpoints include radiographic progression-free survival (rPFS), response evaluation criteria in solid tumors (RECIST) response, and time to first symptomatic skeletal event.
We should be clear that the trial is designed to identify an average 3-month increase in overall survival if Arm A is shown to be more effective that Arm B, but some patients might do better than that. The trial has also been designed to facilitate approval of 177Lu-PSMA-617 for the treatment of recurrent mCRPC if this drug is shown to be effective and safe.
Endocyte states that enrollment into this trial will probably start soon and is expected to be completed within 18 to 24 months. This implies that a first interim assessment of OS could occur as early as the second half of 2019. However, as yet there is no sign of the more detailed summary of the trial structure on the ClinicalTrials.gov web site and we don’t know exactly how many sites will be recruiting patients or where those recruitment sites will be. Our guess is that recruitment sites will be situated in the USA, in Canada, in several major European counties, and in Australia, but there may be others.
At this stage we suggest that patients who are interested in considering enrolling in this trial may wish to contact Endocyte by using their contact us form on their web site.
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Filed under: Drugs in development, Living with Prostate Cancer, Management, Treatment | Tagged: efficacy, lutetium-177, outcome, Phase III, pivotal, PSMA-617, safety, trial |
THE "NEW" PROSTATE CANCER INFOLINK 
Hi.
This trial aims to detect a significant prolongation of overall median survival. I have the privilege to read to protocol. My only objection is view on sample size. My guess is the trial will reach a definite outcome of longer overall survival with less than the 700 participants asked for in the protocol.
The web site should also refer to another randomized trial. The Australian and New Zealand Urogenital and Prostate Cancer Trial Group started a trial in January 2018. It is registered in ClinicalTrials as NCT03392428. The trial will recruit 200 patients. The trial compares cabazitaxel and 177Lu-PSMA-617 RLT. Th goal is to see whether the new drug is superior to the established treatment. The trial is also supported by Endocyte.
Both trials aim to bring evidence-based medicine to the new drug. So my guess is that in a few years we have at least two trials that give the new drug a place in the sequence of treatment.
PSMA guided Lu-177 is currently available in the US in a Phase 2 trial … Houston and Los Angeles are two known locations. Endocyte participates in these trials partially staffed by European technicians experienced administering Lu-177.
The trials are expensive — around $7,000 to $12,000 patient outlay per session; and treatment involves four sessions. I am aware of at least two participants, both of whom have exhausted all other approved treatment options.
One patient has done three treatments and is seeing results; the other is about to start.
Dear Finn:
It is certainly possible that the new Phase III trial might be able to show results with fewer than 700 patients. That’s why one has interim analyses. However, developers also need to ensure that there are plans for patients to be enrolled into the trial to meet very specific risk/benefit criteria that do not necessarily conform to the hopes of the developer regarding efficacy and safety. Drugs that are expected to show high levels of safety and efficacy in clinical trials fail to do this all the time!
NCT03392428 is an interesting Phase II trial but it is almost certainly not a large enough trial to meet criteria for approval of 177Lu-PSMA-617 RLT by regulatory agencies unless it were to show an extraordinarily high degree of efficacy.
Dear Rick:
The study you refer to is this one. And something about this trial doesn’t “smell good” to me if patients are being charged money for treatment. Costs related to participation in clinical trials should not include any costs for the use of unapproved products so that there are no biases related to who can be enrolled into such trials.