Are you currently (or have you been) in a Clinical Trial?
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A new paper out finds that lasofoxifene, which is currently used to treat ESR1 mutant cancers, is also effective on endocrine-resistant breast cancer cells that do not have an ESR1 mutation but instead have lower ER and increased Her2 levels…
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Cure-ious-I am one of the ones who suggested MSM. I've been taking it for maybe 4 years now. I don't want to sound vain but I get a lot of compliments on my hair ☺️and I wonder if it has had other positive effects on my cancer. Who knows? I'm still alive and kicking so it can't be hurting me too much.
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Lauren @cblaurenceauthor - that is just great news. Time to celebrate a little and kick back & relax.
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I sure could use a beer, haha, but my liver wouldn't appreciate it!
Thanks, @cure-ious Yup, we gotta win sometimes! :)
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Chicagoan, Well, thanks again for suggesting MSM!!! Has it had any effect on your ALT or AST levels? When I dropped Verzenio my hair improved a bit but its still just barely-there, and I refuse to move to a wig. I just bought a bag of MSM crystals (the horse tablets were too much for me) and I wonder if I should take collagen supplement as well? But you see MSM helping your hair even without collagen, is that right?! Dang I hope this works- did it help your nails as well, or mostly hair? I wonder if there is overlap in mechanism of action with the sulphorane of DIM/I3c…
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Cure-ious-I tried collagen before MSM. It did nothing for my hair or nails. I put MSM fast dissolving crystals in water. It is the first thing I drink every morning. It took about 6 months for me to notice improvement in my hair but it has made a great difference. New hair obviously has to grow and that's why it takes time to see results. My ALT and AST levels are very good.
When I need to move to a wig I plan on getting something like the woman boss in Night Agent. She has fairly long grey hair-I read an interview where she said it was a wig and thought-Aha-that's what I'll do when the time comes. But hopefully that won't be for a while.
My nails are still a disaster-I need to keep them very short because they crack off. They are not as bad in the summer but really bad in the winter. Maybe collagen would work for you but I was very disappointed.
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Thanks so much, Chicagoan- I've stopped coloring my hair and had it cut very short, and actually wish I'd done that years ago because its a lot more flattering on my face, but the thin-ness is kinda shocking and there is not much one can do for styling. So I will give it a long time and hope it fills out and strengthens- it would feel so great to fix this, and my daughter is getting married next year, I told her if I can't fix it I will be there in a Dolly Parton wig, yikes…
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@chicagoan - where do you buy the MSM fast dissolving crystals supplement? I need to try something for my hair :/
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Cure-ious-I hope that the MSM works for you. It seems like you should have enough time before the wedding but a Dolly Parton wig would be fun too!
Aprilgirl-Your hair looked good to me but here is the link for what I buy on Amazon:
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Good news continues so far on the KAT6/CDK4 trial I am on. Tumor markers plummeted after 4 weeks and continue to decline. CA27-29 almost normal at 46. Liver mets are smaller and bone mets started to respond at about 4 months. SEs are minimal, mostly fatigue, I nap daily. I can do most activities, just need to pace myself! Taste is off, especially for salt. Eyes very dry but recently found some eyedrops that seems to be helping. But my finger nails are the best they have been since I was originally diagnosed!
Here is the trial information:
It is so great to see activity on this string again! I always learn so much from everyone.
Cure-ious - what a remarkable response to an unconventional combination! Hoping it continues for you for a very long time!!
jsniffs - how are you doing on the taxol+capivasertib? I too have the AKT1 mutation and my ER+ moved from 95% to 10% and HER2 from 2 to 1. So guessing if we cant target the AKT1 at some point I will also be triple negative.
Lauren - Wow, congratulations! Sounds like you have a great oncologist!
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With a picture just because I really like to look at this one!!!😁
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Wow @perky2020 !! Such great news! Gotta love those tumor marker drops!
Thanks for the link to the trial - it's available in San Antonio and Houston for me, so this will be the first thing I ask about when the time comes. So thrilled it's working for you!!
The Halaven is still working—tumor markers dropped another 350, so I'm at 450 from a high of 1200. Far from normal but headed in the right direction. Trying not to get too excited and my hopes up for a long stretch and just going from blood test to blood test. :)
Best to everyone!
Lauren
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Wow, Perky, I would look at that chart every night, nothing as marvelous as when a drug combo shuts the cancer down completely!!!
Thanks for posting the trial, great that its at UCLA and UCSF, its probably not for me because it might not handle the ESR1 mutation, but will look into that question to be sure…
And Lauren, I'm so so so happy for you, was actually coming on today hoping you were doing well… What a great summer its turning out to be!
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Hey Perky, there is a report out from last month in Nature Medicine (v highly-rated journal; data must be very good) about your trial!!!
Abstract
Inhibition of histone lysine acetyltransferases (KATs) KAT6A and KAT6B has shown antitumor activity in estrogen receptor-positive (ER+) breast cancer preclinical models. PF-07248144 is a selective catalytic inhibitor of KAT6A and KAT6B. In the present study, we report the
safety, pharmacokinetics (PK), pharmacodynamics, efficacy and biomarker results from the first-in-human, phase 1 dose escalation and dose expansion study (n = 107) of PF-07248144 monotherapy and fulvestrant combination in heavily pretreated ER+ human epidermal growth factor receptor-negative (HER2−)metastatic breast cancer (mBC). The primary objectives of assessing the safety and tolerability and determining the recommended dose for expansion of PF-07248144, as monotherapy and in combination with fulvestrant, were met. Secondary endpoints included characterization of PK and evaluation of antitumor activity, including objective response rate (ORR) and progression-free survival (PFS). Common treatment-related adverse events (any grade; grades 3–4) included dysgeusia (83.2%, 0%), neutropenia (59.8%, 35.5%) and anemia (48.6%, 13.1%). Exposure was approximately dose proportional. Antitumor activity was observed as monotherapy. For the PF-07248144–fulvestrant combination (n = 43),the ORR (95% confidence interval (CI)) was 30.2% (95% CI = 17.2–46.1%) and the median PFS was 10.7 (5.3–not evaluable*) months. PF-07248144 demonstrated a tolerable safety profile and durable antitumor activity in heavily pretreated ER+HER2− mBC. These findings establish KAT6A and KAT6B as druggable cancer targets, provide clinical proof of concept and reveal a potential avenue to treat mBC. clinicaltrial.gov registration: NCT04606446.- not evaluable= means some people are still on the drug for longer than the 10.7 months, how long have you been on this?
- When they are already getting good numbers for PFS in a phase 1 trial, you know its promising…
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Yes, that is my trial! I started in December. I understand it is going well world wide. They have even started a new arm of 3 weeks on and 1 week off to see if they can address the SEs.
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Hi All. I've been off the boards ever since the decision to possibly leave the RLY-2608 trial (targeted PIK3CA drug). Just needed to take a break, clear my head, and distract myself with life. The two marker liver lesions were growing in very small margins, bone scans are stable but TMs going up quite a bit. I stayed on the trial for a few more months but last week, despite fairly stable scans, MO and I decided to switch to Truqap. Interestingly, my last Guardant showed the PIk3ca mutation was higher than before and the ESR1 mutation disappeared (although from what I gathered from discussion with MO, the fact that I had an ESR1 mutation before may affect treatment choices? Perhaps going back to another AI may not be as effective since the mutation was there and "disappeared" as opposed to never having ESR1?? Not sure but have that on notes to discuss again).
Waiting for Guardant results before final decision on Truqap but that seems to be the likely next step. I'm so saddened by news of RK2020. I never did respond to her comment. So many losses of loving and generous people on this board. And to see the news about Shannen Dougherty just made this a very somber day. Her podcast on MBC was very intense, raw, and honest. I think she was ER+ (same as me). I'm off treatment until Guardant result comes in (hopefully next week) so I'm trying to savor being free of SEs but it's been a gray week and there's that dreaded thought that always comes up when something stops working. . . Thanks for listening and hope everyone is staying well.
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SmallMoments, Thanks for the update, how long did the RLY-2608 last? One thing I read was PI3KCA inhibitors have a problem of working well but not lasting very long. Did you try adding Celebrex? not only does it block PI3KCA, but one of the main targets of the drug is PDK1, which is one of the main reasons cancers escape inhibition of Pi3KCA. So maybe add it in with Capi to get a longer response and better inhibition?
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In the figure below, you see Celebrex blocks PDK1 upstream of AKT:
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Dear Cureious, are there some to you known Celebrex trials to know the dosage, scheduling, etc.? Saulius
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Thanks so much, Cure-ious. I was on the trial for about 21 months. Quite good and I'm grateful. Thanks also for the Celebrex info. I read your posts about the Faslodex, Celebrex, Enobosarm with great interest. I will definitely look into getting Celebrex. Really appreciate it.
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Saulius, There are not any trials of Celebrex or related drugs that I know about specifically for MBC cancers with PI3KCA mutations, which I find very discouraging given that the link with PI3KCA was reported in NEJM long ago ( 2011), and has been borne out in papers looking at different cancers since then. So many women could have potentially benefited in the meantime! However, I did see where it was included a clinical trial for colon cancers with PI3KCA mutations (testing in combination with another trial drug for PI3KCA) that I think started this spring. If I can find the trial, I will come back with the link.
For me, when I had some starting progression in a couple of scans and couldn't find a trial to take, I added one Celebrex at night (standard 200 mg dose) and my TMs dropped, so the standard dose was sufficient. I was still on Verzenio at that point and didn't want to add a second dose (regimen is supposed to be 2x/day) but then later on I dropped V and added the second Celebrex and my TMs dropped even more significantly (probably the V had stopped working), and it has been stable since so far. So all I did was add one pill, test TMs a month later, add the second pill, see if it helps…
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@cure-ious, just curious (no joke intended), did you already have a script for celebrex or did you have to convince your MO to prescribe it off-label for the PI3KCA mutation?
My wife, so far, doesn't have that mutation but I like to keep options in the back of my head in case we ever get there. She recently asked her MO for a celebrex script just for joint pain as she has been having "trigger finger" in her ring finger which is usually pretty well associated with estrogen deprivation, but he told her it could damage the liver and prescribed some exercises instead to relieve inflammation of the fascia.
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Bighubs, I did, for arthritis pain, however though I had the medicine on hand, I did not take it for a long time, because there was a paper in the literature that had combined Celebrex with a CDK4,6 and it was not helpful and indeed made things somewhat worse. So I decided as long as I was on a CDK4,6i, I would not take Celebrex. And testing before then did not show a PI3KCA mutation, it only showed up in Guardant that was done after progression, and indeed that mutation is one cause of progression. I had been on Femara-Ibrance, then Faslodex-Ibrance and then swapped the Ibrance for Verzenio. So when the latter stopped working, the cancer had both ESR1 and PI3KCA mutations. After fiddling around with keeping v dropping the Verzenio (which did not change my TMs and made me assume the cancer was resistant) I ended up taking enobosarm off-label from Chemyo, and added in the Celebrex. That combo is very strong I think (at least for my cancer) because my TMs got lower than ever and I was very happy to have arthritis pain relief too! I do think its useful to get a Celebrex prescription so that if you develop the mutation you can give it a try- if I were taking another med for {PI3KCA, I would try adding it in later, after it was clear the first drug was working, and follow TMs to make sure it helps.
I guess I'm now 8 months out on enobosarm and Celebrex. I might be doing the same had I taken Elascestrant and added in the Celebrex. Benefits are zero fatigue and building up lean muscle, good thing for us, and having some more energy. Its quite subtle effect. Others on this site taking enobosarm might want to chime in!!
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BigHubs, Also melatonin can be a good inhibitor of Pi3KCA, and I bet you the best would be these new weight loss drugs, like Ozempic- not tested for cancer yet but do inhibit PI3KCA in the lab, and have positive effects on organs
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Cure-ious,
I just started taking Celebrex a few months ago but am still on Ibrance. Do you think I should stop until I switch treatments? TIA.
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chicagoan, Its just one paper in the literature where they mixed the drugs and they didn't get a benefit over either alone, so thats far from knowing what they might do in the body. If your TMs are sensitive to the cancer, then you could drop the Celebrex for a month and see what happens. I had to drop Celebrex becuase it caused my creatine levels to go up, and I have one kidney that doesnt function well, so it like aspirin and NSAIDs can damage kidneys. i think the new Ozempic type drugs might do the trick for Pi3KCA cancers too, and they are protective of kidney. However, I haven't seen any paper where that category of drug has been tested for potential anti-cancer activity.
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A new paper in Nature Communications shows that inhibiting the Cpt1a protein together with a ketogenic diet or with Her2-monoclonal therapy significantly reduces metastasis. The loss of Cpt1a promotes a strong anti-tumor immune environment that helps the Her2 therapy work better and avoids resistance.
*Cpt1a inhibitors are already in development for colon cancers
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Dear Cureious and others, sorry, I was away. I have asked about Celebrex because some years ago when my wife had a surgery we were advised by one scientist to take Celebrex before, during and after surgery to, sort of, control the inflammation… Now we can see that this drug also interferes with PIK3CA pathway which is a very interesting thing. Hugs,
Saulius
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Saulius, I was wondering if the new Ozempic-type drugs might also work for PI3KCA mutant cancers, as they are reported to inhibit PI3KCA/mTOR pathway. And, unlike Celebrex, they are not hard on the kidneys,actually they are protective of kidney and can even reverse chronic kidney damage to some extent. Of course, we don't need to lose a lot of weight, but maybe they might help the efficacy of PI3KCA inhibitors at low doses?…
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Dear cureious, hmm, that is interesting - so many drugs could interline in different diseases. Some years ago the topic "repurposing" was heard more but now I do not read much about that:/ Your example of Ozempic-type reminds me of metformin. My Sandra still takes 500 mg Metformin for one month and then one month off for many years already. We do not know if it does something for her but metformin being able to inhibit several pathways is well known, and taking it might seem logical because she had liver disease… anyway, maybe one day we'll get some repurposed drugs like in APLeukemia story where some sort of vitamin A or its derivative is used to achieve cures and one scientist, if I remember well, noticed it because one arm of clinical trial used to eat more carrots… crazy:)
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