AMPLITUDE clinical trial

[Benkaymel]

Having been diagnosed with stage 4 PCa in May this year (see my profile for more details), my CO has suggested it could be worth me participating in the AMPLITUDE trial. This is currently at the stage of taking newly diagnosed metastatic cases like mine who have particular DNA repair defects. I don't yet know whether I have these defects and they can't test me for another few weeks. It will then be a further few weeks before I would start on the trial if I do it. Also, being a double-blind trial, I might be in the placebo half anyway. I had my first ADT (Prostap) injection 3 weeks ago.

AMPLITUDE involves adding a PARP inhibitor (Niraparib) to enzalutamide that I will be starting at the same time.

Has anyone been on this trial or know anything about it? (prior results? risks?)

Should I wait until mid to late September to see if I qualify, or just get started on enzalutamide now and forget the trial?

Any views or knowledge would be welcome, thanks,

Ben

[Tall_Allen]

There have been 2 trials of PARP inhibitors combined with Zytiga. One showed a good response in all patients. The other showed a good response in only those patients with homologous recombination repair defects. I'm not sure why they came out different.

meetings.asco.org/abstracts...

meetings.asco.org/abstracts...

[Benkaymel in reply to Tall_Allen]

Thanks Allen, so if I do have the repair defects, it sounds like it would be worth me waiting for the trial. My CO said as long as I start enzo within 12 weeks of the first Prostap injection, it will be OK.

[Benkaymel]

Good point. I'll ask my CO about that.

[hopeful1956]

My husband was diagnosed (at age 65) Stage 4, PSA 8, Gleason 7 (4+3) oligometastatic (1 bone met on pelvic bone Aug/21. Had genetic testing. Positive for BRCA2. Started Amplitude Study Jan./22 (in Canada). Double blind study so neither he nor MO know if he's on placebo or Niraparib. He's tolerating the meds fairly well. Gets hot flashes and feels blah at times. Zoladex shot every 3 months. PSA undetectable. Nothing has spread. Blood work is fine. Good luck Benkaymel on whatever you decide!

[Benkaymel]

Thanks hopeful, sounds like your husband is in a similar position to me (although I'm still waiting for my CT scan results to see if I'm high or low volume (oligo)). Good to hear he's tolerating the meds but of course, we don't if he's taking the PARP or a placebo. I'm still mulling over whether to join it if I am eligible. One factor against is that I'm not keen to take Abiraterone + Prednisolone but would rather take Enzalutamide due to better SEs. I've asked if this would be possible on the trial.Good luck on your husband's journey!

[MateoBeach]

You were/are de novo metastatic (at diagnosis) and recently so. I would go with the proven winner: Triplet therapy adding docetaxel and darolutamide both to the ADT. Darolutamide has just been approved for this. Vs. Waiting for uncertain genetic analysis and questionable benefit if no HHR gene mutations and possibly on placebo. If you do have an actionable gene mutation likely to respond to a PARP, that will still be a possible treatment down the road. Play your strongest hand first is what I would do.

[Benkaymel]

Thanks Mateo,

I appreciate you are an advocate of triplet therapy, but I really do not want to clobber my body with chemo on top of everything else unless I really have to. I’ve studied the various triplet trial results and the long-term OS compared to doublet therapy (ADT + AR) is not that significant – especially when you add in the time that chemo would still add as a potential follow-on treatment. I will have enough on my plate as it is dealing with the SE of hormone therapy. I’m erring towards forgoing the AMPLITUDE trial and getting started on Xtandi in addition to the Prostap.

I’m also doing a lot to help myself including a plant-based diet with no caffeine (apart from green tea) and virtually no alcohol. I work out on my home gym 4 or 5 times a week and go for regular long walks. I also take various supplements including Pomi-T, vit D, turmeric, lycopene, milk thistle, etc. and although unproven and may be of no benefit, I’m continuing with Salvestrol and grated frozen lemon on most meals.

For all of us, time will tell how effective our treatment choices turn out to be and I wish everyone the best of luck with their approach.