Lu-177-PSMA-617 VISION trial suspended temporarily for new recruiting

[Tall_Allen]

Many are interested in this trial. I just received notice that it is temporarily suspended. The problem is the very high drop-out rate among those randomized to the control group in this trial. They are reviewing the trial protocol to see if they can fix it. The control group receives standard-of-care at some of the top institutions in the US, Canada, the UK, France and other countries (52 sites so far). Those who are already in the trial will continue to get the care they were randomized to.

[cesanon]

Why do you think people are dropping out?

What are the two different legs of the trial?

[Tall_Allen in reply to cesanon]

I think those who are randomized to standard-of-care are either engaging in medical tourism (e.g., Germany, India, Australia ...) where they can assuredly get the radiopharmaceutical, or they are electing to get standard-of-care locally from their own medical oncologist. I suggested they adopt a crossover-type design where the control group gets the radiopharmaceutical after they have shown radiographic progression on standard-of-care. But that's their secondary objective -- It wouldn't allow them to show an overall survival benefit, however, which is their primary objective.

[Teddysdad]

Thanks for the update on this as I am looking at this as an option but don't think the trial is recruiting is recruiting in the UK yet.

Not sure how I would feel if I were randomised to be in the control group and the progression of my cancer means I have to do something.

While I don't fully understand what 'standard of care' means and would entail I would be looking for something and might elect to go abroad to Germany where I believe the treatment is available.

I would have thought there are enough patient whose data they could use to measure against.

[Tall_Allen in reply to Teddysdad]

It is, or was, recruiting at seven sites in the UK as well as elsewhere in Europe (France, Denmark, Netherlands and Sweden). They may not be having the same problem there as in the US - people are more willing to be randomized in Europe - so check with them.

clinicaltrials.gov/ct2/show...

"Standard of Care" means any of the treatments that are approved in your country for advanced PC. In the US, that would include Xofigo, Provenge, Docetaxel, Cabazitaxel, Zytiga or Xtandi, as well as any supportive therapy needed to maintain quality of life.

They cannot use historical data to prove a survival advantage - it has to be randomized so that the treatment and control patients are nearly identical. (The trial is designed to randomize patients 2:1) So far, we know that Lu-177-PSMA-617 effects PSA, but we can only guess that it delays further progression and extends survival too.

[EchoII in reply to Tall_Allen]

Approved by who?

[ctarleton in reply to EchoII]

In the USA it's the U.S. Food and Drug Administration (FDA). Other countries have their own approval bodies.

[GaryG1950]

I would be curious to know who notified you this trial was being suspended. Our clinic and research network in Omaha, NE has significant involvement with this trial and is constantly enrolling new pts. We have had no notices it is suspended. I would be very surprised at the accuracy of this information. Can you post a copy of the notice, where it came from and the exact content? I'm afraid pts are being misled by this report.

[Tall_Allen in reply to GaryG1950]

I didn't say the trial was being suspended, I said new recruitment is temporarily being suspended. The notice came to me from Jeremie Calais at UCLA. He said Endocyte is looking at revising the protocol because they are having trouble retaining the control group:

"From today, UCLA cannot enroll new patients in the 177Lu-PSMA-617 VISION randomized phase 3 trial until further notice.

The sponsor needs to amend the protocol to fix the issue of the high drop-out rate in the control arm."

If the trial protocol is changed, it affects all sites. Perhaps you should contact Endocyte to obtain clarification.

[GaryG1950]

Thanks for clarifying your statement, Tall Allen. It was apparently confusing to others....we had three of our patients contact us asking if the trial was ending based on your post. This could also just be an issue with UCLA. We have not been asked to suspend our recruitment activities. And yes, we will certainly talk with Endocyte and report back.

[Tall_Allen]

Thanks - I will be interested to hear.

[joekaty in reply to Tall_Allen]

Agree they need to revise their approach to keep enrollees assigned to the control. My husband starts docetaxel again next week after xtandi failed and scans show new mets I’m vertebrae. Our intent was to do enough docetaxel so that he would qualify for the study as he was not castration resistant when he finished 9 rounds a year ago. If he was assigned to control arm our intent is to go to Germany. We’re at UTSW.

[Tall_Allen in reply to joekaty]

I suggested that they revise the protocol so that men assigned to the control have the option of getting the drug after any new mets are discovered with Ga-68-PSMA-11 on subsequent PET scans. That would at least allow them to arrive at a hazard ratio for radiographic progression-free survival (rPFS), but they would lose the ability to determine whether there is any overall survival advantage. The FDA would have to agree that that is enough to grant approval, though.

Alternatively, they can rely on sites in the UK and Canada where medical tourism is lower. It would take longer to accrue adequate sample size, however.

[NOCanceros]

Hello Tall_Allen

Allen i wonder about 1 thing ,it was 2 days holidays ( Eastern days) in Germany and i missed therapy treatment 2 times and i told the Onkology can i rebook my flight he said no i can give you double dose of therapy to compensate the lost. what do you have for suggestion or idea about this situation. Double dose can harm my body or kidneys. ( The case is my Treatment of lymph nodes) Thanks

[Tall_Allen in reply to NOCanceros]

I guess he thinks you can tolerate the higher dose.

[Roast85]

Have you received any updated information on this?

[Tall_Allen]

I have not yet pursued. I suggest you contact them. Let me know!

[Fairwind]

On September 12, 2019 in Denver I was told by the doctors supervising my Vision Trial treatment that the trial had reached the desired number of participants and was no longer accepting new applicants...

The original trial was sponsored by Endocyte, they set the rules and procedures. Last February, Novartis, a huge Swiss pharmaceutical company purchased Endocyte for $2.1 Billion cash.. This change made waves at the facilities contracted to actually perform the trial and the number of locations doing the trial expanded rapidly..

The men who had passed their PSMA scan then got "randomized" into two groups, 2/3 getting the Lu-177 and 1/3 getting "standard of care" . Everybody was supposed to get SOC, even the men selected to receive the Lu-177. In practice, it didn't work out that way.. Most of the men who joined the trial had already endured and failed SOC treatments..Many (most) of those men randomized into the control group dropped out and returned to their existing treatment facilities. Leaving the trials sponsor in a quandary..

So here we are in September, they have closed the trial to new participants, and I guess they hope to get FDA approval based on the evidence gathered even without the planned on SOC only control group..

[Tall_Allen in reply to Fairwind]

I think they made a mistake in not allowing Xofigo in the SOC, since it certainly is SOC. I'm guessing they were afraid that Lu-177-PSMA-617 might not hold up in a head-to-head trial.

[Casper3]

This may not be the proper site to ask this question but is there any where you can get this drug in the US or Canada?

Is there any time schedule for the FDA to approve the drug?

[Tall_Allen]

They've stopped recruiting for the VISION trial, but it will probably take a few years until enough time has lapsed to observe a survival benefit. UCSF is testing it with Keytruda. Weill Cornell is testing different ligands and Ac-225. There is a trial of Th-227 and of I-131 in the US and Canada.

[Bangkok]

I'm heading back to Bangkok for another round of radioligand. I am a one off. I basically had a couple weeks of hormones then a month later started first of 3 rounds of Lute 177. My PSA dropped from 986 down to 0.10. 7 months later my PSA is starting to double so I'm going back. Everyone is interested in my response since I am not the usual patient.