splash trial

[Happy1985]

my husband and I are running into an odd situation with the splash trial. He is in the control arm and past 2 scans show disease progression. The folks at Penn, his oncologist and the dr leading the trial (where he is being treated) agree his disease is progressing. According to the trial “rules” he is eligible for cross over. However, the folks for the drug company who approve crossover say he has not progressed. We are extremely frustrated and do not understand how this could happen. Penn is known for their work with cancer and we assume the the splash trial folks are also very experienced. So now he is going for a 3rd scan psma pet scan. Has anyone run into this situation? We have been told it is quite unusual.

[6357axbz]

please define progression

[Happy1985 in reply to 6357axbz]

2 lesions on each adrenal gland that have increased between scans, rising psa and new spot on liver. Dr says next scan should help in determine if it is cancer or not.

[Tall_Allen]

Suggest you have an FDG PET scan too, in case the progression is non-PSMA avid. If that is the case, you wouldn't want to cross-over.

[Happy1985 in reply to Tall_Allen]

thank you. Have not heard of that type scan.

[Tall_Allen in reply to Happy1985]

FDG PET is the most popular PET scan. It is used for most cancers. IMO it should always be used to find discordant tumors whenever a PSMA-targeted radiopharmaceutical is planned, for reasons described in this article:

prostatecancer.news/2019/12...

[Mcrpca in reply to Tall_Allen]

What do they really mean when the trial says a drug “extends life for 13.6 months” or “4 months longer than the control?” What the heck is the starting point??

[Tall_Allen in reply to Mcrpca]

They randomly assign one group of men to get the drug (called the "experimental group") to another identical group who don't get the drug (called the "control group"). They compare the lifespans of the two groups.

[Mcrpca in reply to Tall_Allen]

I understand clinical trials. I just don’t understand the starting point. 4 months longer based on what criteria? Onset of diagnosis? That would be tainted by the fact that men are diagnosed at different stages. Onset of castrate resistance? Time from entry to the clinical trial to death? That would have tons of variables that would be difficult to control for. Do you see my confusion? Thanks for the discussion. I respect your views.

[Tall_Allen in reply to Mcrpca]

Every clinical trial has its own criteria for inclusion and exclusion. You have to look at each separately. In the one the OP is talking about, SPLASH, everyone has to be castration resistant, and failed one of the second-line hormonals, and not yet used chemo while castration-resistant.

The variables are controlled for by randomization and having hundreds of men in each group.

[lewicki in reply to Tall_Allen]

Should this always be done ?

Thanks

[Tall_Allen in reply to lewicki]

IMO

[lewicki in reply to Tall_Allen]

likewise

[tango65]

In general in these trials, they use Recist criteria to define progression:

uptodate.com/contents/image...

"≥20% increase of at least 5 mm in the sum of the longest diameter of the target lesions compared with the smallest sum of the longest diameter recorded

or

The appearance of new lesions, including those detected by FDG-PET"

If the lesion in the liver is PC, then there is progression by Recist criteria. Was the liver lesion PSMA positive?

[Happy1985]

thank you to clarification. We will know about liver after scan on Fri.

[tango65 in reply to Happy1985]

Best of luck!!

[tango65 in reply to Happy1985]

My understanding is that Recist criteria does not include PSMA PET/CT findings but they do include FDG PET/CT. Prostate cancer mets are usually FDG positive (even when PSMA negative).

Consider discussing about crossover if the liver lesion is PSMA Positive and they do not do a FDG PET/CT.

[dhccpa in reply to tango65]

Where does Axumin PET fit in compared to PSMA and FDG? Thanks.

[RyderLake2]

Hello,

A lot of similarities here. I too am on the SPLASH trial and also on the control arm. I am currently on Zytiga (abiraterone) plus Prednisone. The clinical trial team switched me to Zytiga after nearly five years on Xtandi (enzalutamide). My PSA is also rising, albeit slowly. My last PSA in mid-June was 1.6. I will be getting another PSA test tomorrow. At diagnosis, ten years ago, it was 1700 (no typo). When I asked my team about crossing over to Lutetium, they said it depended not only on a rising PSA but also evidence of progression on scans. They go hand-in-hand. If your PCa has spread to your liver, and if it is PSMA positive, then I think the POINT Biopharma folks who are running this trial and who determine who gets into which arm will be giving you the green light soon to crossover. Good luck!

[Happy1985 in reply to RyderLake2]

thank you for your reply. It’s very frustrating as this has been going on since April and penn does not know why the biopharma folks see no progression when they clearly do. Hoping scan on Fri convinces them.

[joeguy]

Im not sure about the drug company people running Splash. I was in the Lu177 arm in Dallas, and was kicked out of the trial after just one dose for “progression”. My doctors at home in Tulsa believe the “progression “ they saw was actually the drug starting to work. PSA value started declining rapidly right after the drug company kicked me out.

[Seasid in reply to joeguy]

Interesting

[dadsdrdawn]

I cannot imagine your frustration. Is there a "discrepancy" of the use of the word progression between insurance company or doctors?

Forgive my layman's terms on this site, I know that most people use exact numbers, and measurements...but I don't know that that is necessary for this.

Maybe it is not progressing, but has not changed?

With my father, it progressed, meaning the largest tumor got bigger. So, he was cut from the trial and is now on Zytiga and Prednisone...and had 5 radiation treatments to the spot on his spine that was causing extreme sciatic pain. He has been nearly pain free since a week after the last treament.

I would get the clarification on this.

Praying for your strength and healing,

Dawn

[Happy1985 in reply to dadsdrdawn]

thank you. He has clearly progressed just based on the lesions on adrenal glands growth and psa. They are hoping this weeks scan proves beyond 100%. I just do not understand how 2 institutions can not agree on this since it has been ongoing since April.

[dagreer]

I noticed this tricky wording of the trial on the BioPharm's website:

Ensuring Access to 177Lu-PNT2002

Participants who are receiving standard of care and experience progression of their disease (confirmed by radiologic testing) may be eligible to switch therapies to 177Lu-PNT2002. Participants from both parts of the study will receive long-term follow up for up to 5 years.

[Happy1985 in reply to dagreer]

I understood the term ‘may’ is to ensure the participant still qualifies just as they did initially. That has not changed for my husband, he still works, exercises, eats great etc., basically living life.