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Are you currently (or have you been) in a Clinical Trial?

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  • husband11
    husband11 Member Posts: 1,287
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    Husband, I was just wondering if it would help w/stamina- does it help w/hair loss too? And how did you determine dose (powder or liquid)?


    We just went with the 9 mg that were found to have the most benefit in the trial that tested 3 different doses.

    As its a non steroidal androgen, at high doses (and 9 mg isn't considered high dose), it could have virilizing effects such as exacerbating male pattern baldness, stimulating unwanted hair growth, etc. But you aren't likely to see that at 9 mg which is considered in the bodybuilding world, a very lose dose. We bought it in a liquid form, and just mix 0.3 ml in a glass of juice and stir it up and drink it. The solution is 30 mg/ml in the one we bought. We bought from Science Bio, but they are no longer in the business, as they fear coming regulations of sarms. But, I've heard Chemyo's 3rd party testing is reliable.

    My wife noticed no impact on her hair, good or bad. It noticeably increased the pace and distance of our walks. Put a bounce in her step, so to speak. No impact on liver enzymes that we could see.

  • jsniffs
    jsniffs Member Posts: 136
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    @cure-ious - NIH is going to try to figure out if it's a switch or new primary by reviewing all my biopsy slides. They may do more review, but that is what they are starting with. Different providers I've talked to have guessed differently, so it will be interesting to find out what the NIH says. MSK thought because both clones have a high % of AR, that it was likely a receptor switch (they said straight-up trip neg is more likely to lack AR). That is what I want to believe!

  • rk2020
    rk2020 Member Posts: 697
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    @jsniffs I know you providers have to check and it’s very good that they are being thorough but I’m going to believe this is all the same cancer. If my thoughts and good wishes had super powers, you’d be a shoe in for the trial. Please continue to keep us posted.

  • moderators
    moderators Posts: 8,287
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    @jsniffs 🙏🙏🙏

    @husband11 thank you for sharing that. We too are interested in more details for your wife. @luce mentioned "9 mg of enobosarm is the dose they used in trials".

  • luce
    luce Member Posts: 354
    edited September 2023
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    Well, they used 9 mg and 18 mg in an earlier trial and both doses were well tolerated but 9 mg did slightly better, so 9 mg is the dose used in phase 3 trials.

    https://www.cancernetwork.com/view/fda-grants-fast-track-designation-to-enobosarm-in-ar-er-her2--metastatic-breast-cancer

    https://classic.clinicaltrials.gov/ct2/show/NCT04869943

  • jsniffs
    jsniffs Member Posts: 136
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    Thanks for all the good wishes and positive thoughts. It's amazing to me how helpful the NIH and my own institution have been in obtaining/sharing records. There are so many wonderful people out there trying to make things happen.

  • cure-ious
    cure-ious Member Posts: 2,762
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    jsniffs, There just aren't that many potentially game-changer trials, so I guess when one comes along, we just have to dance thru all those hoops they throw up there…

  • cure-ious
    cure-ious Member Posts: 2,762
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    Excellent, husband, thanks for all the detail!!!

  • mommacj
    mommacj Member Posts: 52
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    Thank you to all who have contributed to this thread. It has a lot of really good information. I appreciate everyone’s insight. I was diagnosed with mets almost a year ago and was on iBrance and faslodex which gave me a mixed response… bones were better but my first pet showed a liver spot. We continued for 8 more weeks to see if I just needed a little more time to respond and there were 3 new liver spots so my oncologist started me on Enhertu. I am ER positive her2 low and have the PIK3CA mutation. Enhertu has been really tough on me only getting 8-9 decent days per cycle but my latest pet showed that isn’t working either with a mixed response again. Liver looked somewhat stable but bones were worse again. I went to UCLA yesterday for a second opinion and to see what trials they had available and the trial doctor suggested a Phase 1b trial with Everolimus and a new drug ARV-471. She thought it would be a good drug for me to try because the ARV-471 would treat the ER pathway and the Everolimus would go after the PI3K-AKT-mTOR pathway. She seemed to think it would be much more tolerable for me than Enhertu and I’m not responding well to it anyway. I came home and did some reading and I’m pretty confused because Everolimus didn’t appear to be very effective or tolerated all that well either… and I know nothing about ARV-471. It’s almost 2 hours for me to LA without traffic… 3 1/2 with traffic and I’m wondering if it makes more sense to have my onc prescribe Affinitor/exemestane rather than go all the way to LA every two weeks for an unknown? Or maybe there is a better trial or better next line since I’ve only had two so far? I am a little nervous about a Phase 1 trial after knowing about the experience Believe60 had. But the trial doc said both drugs have been used on many a patients even thought the ARV-471 is not yet approved. So I’m just contemplating what my next steps should be and waiting to here back from my onc. If anyone has any information or experience with either of the drugs in the trial I would be grateful to hear your thoughts.

  • jsniffs
    jsniffs Member Posts: 136
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    @mommacj - Ugh, I hate when drug decisions have to be weighed against travel. I don't have direct experience with ARV-471, but I can say that during a Dana Farber webinar, they were saying it's quite tolerable and spoke about it like it was amazing. Also, Everolimus = Afinitor, so if you ask your onc about Afinitor/Exemestane, you'd still need to manage side effects from Everolimus. Have you discussed Piqray (alpelisib) with your onc that targets PIK3CA? I'm sure others will have more to contribute. Best of luck with your decision!!

  • newgardener
    newgardener Member Posts: 102
    edited September 2023
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    Mommacj - the trial they've proposed seems interesting. I wonder though if the LOXO trial cure-ious posted about is an option too for targeting the pik-mtor-atk pathway? I only mention it to consider ahead of time because I expect if you did the ARV-471/everolimus trial you might not be eligible to do another trial targeting the same pathway. As you look for your third line you are in a so-called sweet spot that you are still eligible for most trials. After 3 it becomes harder.

    I don't have experience with ARV-471 but it seems promising. I was on everolimus (back in 2013!) in combo with exemestane. I managed to squeeze 12 months out of it; however, I did get a dose reduction because of mouth sores and developed hyperglycemia that I controlled with diet. That said, I was also at peak fitness - did a 10K race even. I'm not sure what dose your trial will use, but it would be good to know if they allow dose reductions if needed.

    I read Believe60's experience with her trial with trepidation. Phase 1 trials are riskier because not a wide group of people have had it. That said, I've been in several Phase 1 trials (including one right now). The time commitment is much greater, but it does drop after the first couple of months. I've also had to travel for my trials. My first one involved monthly trips from Calgary to Boston for 2 years, but other than the travel, my quality of life was so much better than the IV chemo on offer. For this latest trial (NCT05262400), I had to travel from Ottawa to Boston (8 hrs drive each way) every week for 9 weeks. Staying over wasn't an option because truthfully I couldn't afford to get sick in the U.S. as an uninsured person. It was an absolute grind and I nearly bailed midway. But I made it through and now it's just monthly travel and the tumours have shrunk, which has surprised everyone including my home oncologist and the trial oncologist.

    Anyhow, I've rambled too long. Good luck with your decision. I find making a Pros/Cons spreadsheet of my options helpful.

  • cure-ious
    cure-ious Member Posts: 2,762
    edited September 2023
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    MommaCJ- The LOXO-783 drug is specific for the most common PI3KCA mutation, H1047R. The trial for that is available at UCLA-Santa Monica (as is the Everolimus-ARV-471 trial), however I think that the SERD option for that trial (Imlunestrant) may be not yet available, so that the only options at the moment are to take the LOXO drug with either Fulvestrant or an AI. Hopefully the SERD becomes available soon because I would think most people who need LOXO have already had regular endocrine therapy combinations. Also, it is phase one trial and drug doses range from 300 to 600mg, so it would be preferable to wait for phase two. In that respect its good that they do accept patients who have had as many as five prior therapies, do take bone-only mets, and the trial ends May 2025. However, if you do think that eventually you will want to try that drug,keep in mind that the trial excludes any prior treatment for mTOR or PI3KCA, and that would mean no prior everolimus or Piqray etc. So if you take Everolimus-ARV-471, you might not be eligible for LOXO in future, this is the kind of thing to ask the trial people about. The Capivasertib AKT drug hits the PI3KCA pathway and should be approved by year end, but it can only be paired with Fulvestrant for now, as trials are still testing it with SERDs, and I don't know if prior Capi would disqualify you from the LOXO-783 trial (another question for the trial people). The RLY-2608 drug is for all mutant forms of PI3KCA, but unfortunately that trial only pairs it with Fulvestrant. Elascestrant is the only approved SERD and available for those who progress on Fulvestrant, but I think is only available as monotherapy, and best for more endocrine-dependent cancers.

    There seems to be a very large gap right now in good options for those progressing on CDK4,6i with Fulvestrant, this is really complicated in terms of making a reasonable choice, and obviously, its very frustrating.

    PS Newgardener, your experience with phase one trials is very interesting and useful, no need to cut your comments short!!! And, WOW, you have been at this for 13 years?! Can you please write up what you did in more detail, we all need to see how one negotiates this stuff

  • mommacj
    mommacj Member Posts: 52
    edited September 2023
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    jsniffs thank you so much! I haven't heard back from my onc yet about her opinions on the trial. I was kind of thinking that if I do the trial I would still have piqray as an option to try down the road since it's already FDA approved. I am really interested in following the TIL trial and I am praying and believing with you that the biopsies show a receptor switch!!

    newgardener Wow…13 years that is so encouraging! Thanks for the advice. I messaged my trial contact today to ask about dose reductions and they are permitted. That made me feel better because I seem to be somewhat of a drug lightweight. I agree with cure-ious share away because your experience is very useful and inspiring.

    cure-ious thank you so much. I messaged the trial nurse and asked about LOXO-783 as well. It is good to know the right questions to ask to avoid becoming ineligible for a good drug trial down the road. You know so much about these trials so I really appreciate your knowledge. One thing my onc wanted me to look into that she thought would be very interesting is an immunotherapy trial. They typically don't work for ER pos cancer she said, but my Caris report showed a 100% positive result for the PD-L1 biomarker. She said there were only 5 of us in the entire database (out of thousands) that were ER pos and 100% positive for the PD-L1 biomarker.

  • jsniffs
    jsniffs Member Posts: 136
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    @newgardener - You are my hero. I'm amazed at what you have done with clinical trials. I would love to hear more as well.

    To all - Has anyone heard of alternating between Trodelvy and Enhertu (e.g. do 1 or 2 cycles on one then go back to the other for 1 or 2 cycles and repeat)? I realize this is not standard protocol and there are logistical issues with insurance, scheduling, etc. However, I'm trying to figure out if this is a legit possible option if some lesions respond to one and some lesions respond to the other. Thanks!

  • cure-ious
    cure-ious Member Posts: 2,762
    edited September 2023
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    MommaCJ- Wow!!! Fantastic news for PD-L1!!! And that means not just immunotherapy but all the other variations, CAR-T, TILs, testing different combinations of partners that are thought to break down the macrophages that the tumors have protecting them from the immune system.. Only five like you in the entire database?! Well, now you gotta do it, so we know how well the highest end of the spectrum does!!!

    PS Does your genetic testing also indicate anything for tumor mutation burden (TMB)? As I understand it (ie, I don't know much) it seems like a different biomarker for immunotherapy response…

  • cure-ious
    cure-ious Member Posts: 2,762
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    jsniffs, You are super-creative, that's a great idea!! yeah, the system is not designed for this kind of thing, but it seems that there have always been a few people who change things up for a variety of different reasons, and one could imagine not only being able to hit the different mets but possibly also being able to do so for a longer period of time because of not strongly selecting for one mutation or another to become predominant and cause resistance

  • cure-ious
    cure-ious Member Posts: 2,762
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    Hey, MommaCJ, I just remembered, there was a paper awhile back from Richard Finn at UCLA, he is part of that team with Dennis Slamon that first discovered the benefit of Ibrance and were involved in the early trials. He was looking for biomarkers that would indicate response or lack of response to Ibrance, and noted that high PD1 was associated with not having a good response to Ibrance, and that would correlate with your experience there with CDK4,6i!!! And he brought up the idea of kind of an either-or, meaning most people are good responders to CDK4,6i, except those with high PDL-1, and those guys may be more responsive to immunotherapy. I will find the paper and come back and put a link to it.

    More recently, there have been several papers that show that cancers with high tumor mutation burden (TMB) are more resistant to CDK4,6i. TMB is a separate marker that can indicate sensisitivity to immunotherapy. In general, a TMB over ten can qualify anyone with cancer to get a shot at Keytruda, however for MBC, they recently found you need the marker a bit higher, ie TMB 14 and over had 60% response to immunotherapy, whereas cancers 10-14 had only 8% and of course regular low TMB is much worse still. However, I don't know if there is any relationship of PD1/PDL1 levels and TMB, but maybe people with low TMB but still respond to immunotherapy have high PDL1, and vice versa.. Anyway, this could be why you didn't go long with CDK4,6i, and its probably good to drop that in favor of other targeted drugs or IO.

    https://pubmed.ncbi.nlm.nih.gov/31527167/

  • cure-ious
    cure-ious Member Posts: 2,762
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    Also, although tumor mutation burden usually does not change over time for most cancers, it has been seen that it can go up in people who are treated for a long time on CDK4,6i. This might explain why the recent PACE trial found that they got some good responses to adding immunotherapy after progression on I-F alone.. At the least, it suggests to try immunotherapy after I-F, rather than before, unless you have high PD1/PDL1 or high TMB…

  • cure-ious
    cure-ious Member Posts: 2,762
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    some days its good news!: I had a couple scans indicating slight progression in bones, and my MO ordered Guardant 360, which revealed three new things: PI3KCA mutation (0.7%), ESR1 mutation (0.2%) and a large increase in tumor mutational burden, from 1 to 10.5. The tumor mutational burden increase would normally be unusual, however its been noted with people who have been on CDK4,6i for a long time, and is associated with resistance, as are the other two mutations.

    In response, I resumed taking my statin (pitavastatin, 2mg), which I had temporarily dropped, and Celebrex (celecoxib, 200mg), both of which are potent PI3KCA inhibitors. The chart below shows that TMs have returned to normal, will keep on with Faslodex and Verzenio and these two additions, scan again later in the year…

  • moissy
    moissy Member Posts: 371
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    Cure-ious - Happy to hear your great news! Carry on!

  • bsandra
    bsandra Member Posts: 1,019
    edited September 2023
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    Wow, cureious… I love your scientific approach to problems, and no wonder your devotion and analysis leads to results! COngratulations! My wife also took Celebrex for a week before and after lymph node surgery, which I was told is associated with good anti-inflamatory effect… Did not know that it also was a PIK3CA inhibitor - have written it down!

    Saulius

  • chico
    chico Member Posts: 194
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    Cure-ious that is such good and exciting news. I am so thrilled for you.

  • husband11
    husband11 Member Posts: 1,287
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    That is great to hear Cureious!

  • jsniffs
    jsniffs Member Posts: 136
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    Yay @cure-ious! Glad to hear your test found more things to target.

  • newgardener
    newgardener Member Posts: 102
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    Great news cure-ious. Your plan sounds great and good luck for the next set of scans.

  • cure-ious
    cure-ious Member Posts: 2,762
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    Saulius, Its a relatively recent finding that the anti-cancer activity of Celebrex is only seen in cancers (breast, colon, and others) that have Pi3KCA mutations. There are a couple of places it can act: 1) it inhibits AKT kinase; 2) it inhibits COX-2, which is turned on by the pathway; 3) it inhibits PDK-1, a kinase that is also turned on by the pathway, and enables the cancer cells to escape from PI3KCA inhibitors.

  • keris113
    keris113 Member Posts: 45
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    Hi, is anyone here knowledgeable or have the fgfr1 amplification? This showed in my Foindation 1 testing and I saw that it can cause resistance to endocrine therapy and cdk inhibitors. I was curious and also concerned. Any help would be appreciated!

  • cure-ious
    cure-ious Member Posts: 2,762
    edited September 2023
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    Hi Keris, You may have already seen these papers (link below); FGFR1 amplification is indeed one way the cancer escapes from CDK4,6i. They show that in these cells ER activity jumps up to levels that Faslodex cannot handle, so the cancer remains very endocrine-sensitive. To bring it back down, they added in an FGFR1 inhibitor (maybe still only available in clinical trials?), and also saw good cancer inhibition if they added in either PI3KCA or AKT inhibitors, as these are part of that pathway. The authors stress to leave both the endocrine agent and the CDK4,6i in place and just add a third drug to counter the high FGFR and let the CDK4,6i work again. The FDA is set to approve the AKT inhibitor Capivasertib later this year, perhaps it will be possible to add that to your regimen? (As discussed above, celecoxib and/or statins also inhibit PI3KCA/AKT activity, eg you could try adding these and see if they do anything, while looking at clinical trials). The good news is the cancer is still sensitive to anti-estrogens, so you don't need chemo so long as you can beat back the FGFR1.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912842/

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881584/

    https://www.news-medical.net/news/20230605/Clinical-trials-demonstrate-positive-results-from-targeted-therapy-for-patients-with-multiple-tumor-types-with-FGFR-alterations.aspx

    https://www.nature.com/articles/s41467-022-30666-0

  • keris113
    keris113 Member Posts: 45
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    Thank you so much @cure-ious! From what I have seen, FGFR1 inhibitors are still in clinical trials and I don’t know if there are any open yet right now or if I would be eligible at this time or if I have to wait and see when there is progression. I will ask my MO what she thinks though and maybe adding a statin or the other drug. Pi3kca and AKT didn’t show on my testing results though, would that make a difference? I want to ensure these drugs can work for as long as possible obviously.

  • cure-ious
    cure-ious Member Posts: 2,762
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    Keris, If you read the papers, you can see they show it works in cell culture, but for MOs to prescribe it and insurance to pay for it, it has to be an FDA-approved regimen, because otherwise there is no evidence this works in people. In my case, these drugs had already ben prescribed for their regular purpose, so it was easy to take them and see if they did anything to the TM levels. Sounds like your best plan is as you say, wait for progression, re-check the mutations in blood biopsy, and in the meantime check out the FGFR1 clinical trials…