Are you currently (or have you been) in a Clinical Trial?
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Ooh, good to know. Now the Aurora trial has two people in front of me (sigh) and I'm waiting for a callback to see what I can get into next. There's a CDK2 we talked about and the TTX. I'm not sure how long that waitlist is though. But in order of preference, I would want TTX, Aurora, CDK2, then if all of those are unavailable, I'll take whatever the hell is open, haha! (that's not immunology).
CBL
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CDK7, CDK12, etc.. be sure to push them on what the side effects are for these different drugs ( I know you will!) my guess would be TTX might have the least?
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I'd so love to do TTX. They're checking to see how long the wait is for that one. Aurora will be 4-5 weeks at best. I should know tomorrow.
The doctor recommends I stay on the Bria-IMT until my scans on Dec 27th to see if it will work. This is even AFTER my tumor markers jumped 100, my Signaterra jumped, my PD-L1 is 2, my TMB (?) is 5, and he literally said he thinks I will progress again.
I can't get on Aurora until I can give them a date of when I can sign the consents forms. I said tell them Dec 28th! I'll stay on it until then because there's no other choice right now and it might slow it down, but I need to be off this trial. I also asked to take tumor markers in 10 days to see if they're rising abnormally fast.
I said twice, "I know you want to send complete data to the sponsors, but I'm not seeing the logic of me staying on." He didn't comment either time, like, "Oh, no, we're doing what's best for you…" nothing. If they didn't have TTX I'd look at another facility—not that any of the rest would operate differently.
I'll finally find out tomorrow how long TTX is. As long as the process has started for Aurora, I'm okay with doing another round of this one. But I need to make sure both of those irons are in the fire, and any other trial that might help as well.
I don't want to go against the doctors, but come on. My TM are at 400 now. So next time, they might be at 500, and by the time I start something else 1000? What if that doesn't work? How high will they let it go before I go back to SOC? I only have 3 lines left. I need to get to at least TTX and Aurora before my liver craps out.
Ugh. Sorry to rant, I know I'm in a good place, but it's frustrating.
CBL
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@cblaurenceauthor thank you for ranting, it’s so helpful … for you and for us who are reading and learning from your experiences. ! I’m sorry it’s frustrating though and nerve racking waiting.
I have an appt with my second opinion MO at MSK who is looking for clinical trials for me as back up for my next line of treatment. I start taxotere and Carboplatin next week, and then who knows. Nothing has worked for more than 5 months, my progressions have been in the skin of the breast. So I’m trying to learn how this all works, and I wanted you and @cure-ious to know I appreciate all of your sharing. - Rhonda0 -
CBL, I agree with Rhonda, you are doing extremely well under pressure advocating for yourself! These MOs need to understand we are there for treatment, not to improve PFS numbers for their trial!!!
While TTX is a first-of-its kind drug, I'm not sure what I'd do if you can't get that trial or Aurora, mostly because these options are testing new drugs as monotherapy, and its asking a lot given they won't have had much of a track record for efficacy or side effects. I looked at the CDK7 and CDK12 trials, and they seem to be in fairly early stages.The CDK12 one creates DNA repair defects, so its strongest possibility would be when combined with a PARPi, for example. Is MDA an option? They do a lot of phase one trials also, but some of those are testing known strong drugs in combination with something new, stuff like that…
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Thanks @rlschaller & @cure-ious — I learn so much here, it's good to give back even in a small way. Maybe I'll have some positive news soon! Good luck with your treatment, Rhonda. Even with all the ups and downs, it's still a great opportunity—hope it works out for you!
MDA is a distant option. I went to MDA in April of this year. The clinical trial people sent me a consent form—no discussion, no options—and when I turned it down, they were like "Ok" and that was it. I'm not opposed to going back, but I need to see the doctor again, etc., so I don't have time to wait right now.
My other realistic option is Next Oncology—Irvine (15 minutes away) or San Antonio (still a flight, but not quite as overwhelming as MDA). They have a ton of trials, but they are also Phase 1 usually. Theoretically, I can go anywhere, it's just a matter of time before I progress too far.
CBL
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CBL, Given that, I'm going to backtrack about CDK12/13, if they say the SEs are tolerable I would have it on the list, the company is a good one- and its got a molecular glue degrader of CycK in addition to inhibiting CDK12, at the least in lab studies this will definitely screw up a cancer cell significantly (!!)… Interested to learn what you find out about all these new trials…
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PS I was just thinking I would put CDK12 ahead of Aurora A (assuming SEs were equally tolerable) so I googled that question:
AI response: Based on current research, CDK12 is generally considered a better cancer target than Aurora A because of its role in regulating DNA repair mechanisms and its potential to exploit synthetic lethality in cancers with CDK12 deficiency, making it a more specific and potentially less toxic target compared to Aurora A which can have broader effects on cell division; however, the best target depends on the specific cancer type and its genetic profile.
PPS It would also synergize with the Keytruda you just got
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Ooh interesting, @cure-ious.
I have this on my April liver biopsy report from Caris:
Which according to Google means: While not definitive, an intermediate CNA result may still indicate a potential target for targeted therapies.
So the Aurora (AURKA) is somewhat prevalent, and the FGFR1 showed up (albiet 2.6) on my Guardant last year. There is a FGFR1 trial at NEXT Oncology—I've had pneumonitis, so I might not qualify but it's worth an ask. The CDK12 can move up ahead of that one, and since Aurora won't be open for a while, maybe that one is open now.
So my list in order is TTX, CDK12, Aurora, NUV-1511 (a drug-drug conjugate) FGFR1, and CDK2.
My drug for today still hasn't arrived (around noon) and my nurse will talk to me then about the trials. I'm taking my list with me.
I've decided I do not want to stay on this trial after this week. There's no point in possibly jeopardizing an opportunity to move to something else by staying on something that has a very low chance of working. "Something is better than nothing" isn't necessarily true if it holds me back. I need to put my foot down today. I know they want me to stay with it for reasons already stated, but their stats, as you said, are not my priority.
Will keep you posted on what happens on today's episode of "Adventures in Cancerland."
CBL
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And CDK12 regulates cMYC, again from Google:
Yes, inhibiting CDK12 is likely to significantly decrease MYC activity in a cancer cell, as CDK12 plays a crucial role in regulating MYC transcription by facilitating the proper processing of MYC mRNA at the 3' end, meaning that blocking CDK12 function can lead to reduced MYC expression and subsequently diminished oncogenic activity in cancer cells.
Direct regulation: CDK12 is directly involved in the regulation of MYC gene expression by influencing the RNA polymerase II complex at the 3' end of the MYC transcript, which is critical for proper MYC mRNA production.
- Cancer implication: Due to its role in regulating MYC, inhibiting CDK12 can be a potential therapeutic strategy for cancers that are highly dependent on MYC oncogene activity.
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They all want to eke out as much time as possible on a treatment, and that was obvious in the old days when they didn't have much to offer, but now with a list of possible targeted treatments, it might be better to move along
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Ooh, very interesting about the MYC! CDK12/13 just moved to the top of the list!
Yes, I agree. It's time to move along.
I called my nurse just now and told him I want off the trial and asked to check out the CDK12/13 trial for availability. I'll take the vaccine this week since they have it and I already started the cycle on Tuesday, but that'll be it. We'll see what he says about availability, but if they don't have anything, maybe Irving will.
CBL
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Okay, so not great.
There are waitlists on everything but the CDK2. BG 68501. The doses are like 5, 50, and 200. Not sure what I’m getting yet. I will potentially start that on December 26th. It’s a combo with fulvestrant. It was the last one on my list but it keeps me here and I can start fast. I think the side effects might be an issue, but I don’t have much of a choice. With my luck this vaccine will start to work right when I jump off, haha.
They don’t have any info about how long the wait is for TTX or the CDK12, and aurora a might have a problem with my bupropion. It has a four to five week wait anyway.So I guess that’s it. CDK2 here I come!
CBL
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Now I'm really doubting my decision. The doctor, PA, and nurse all say to stay on this trial, give it three more weeks.
pros: medical staff advising to stay on, they have had PDL1 negative people respond to the PDL1 inhibitor in the combination, not a lot of info that I can find yet on CDK2i.
cons: I've already had progression, my PDL1 is 2, TMB is 5, THE DOCTOR SAID HE EXPECTS PROGRESSION, my tumor markers (before the new drug) jumped 100 points (up from an increase of 30 last time), might lose my spot for the CDK2 trial and will have to wait for something else.
There is a fine line between advocating for yourself and being dumb and ignoring medical advice. But there's not a clear path. My sister is tired of my waffling and doesn't want to hear my thought process, so lucky you…you get all my crazy.
I also asked the trial nurse if I could get tumor markers drawn next week. He said he'd have someone order them but advised they might be inaccurate and to stay off Dr. Google for a while, haha. So I'm not going to do that. They're going to schedule the screening for Thursday 12 and I'll sign the consent form then, so I have to decide probably by Monday which way I'm going to go.
He did finally say that my well-being was their top priority. Good to hear.
Help!
CBL
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If it were me, I'd follow your MOs advice, despite expecting progression, ignore the stupid TMs, see what happens and give your body more of a rest before hitting it with something completely different. Easier said than done, tho….
And I wouldn't be in a hurry to take a CDK2i trial unless I was sure I was going to get a CDK4i as well as faslodex. I've seen plenty of trials where it is being tested as monotherapy or with Faslodex but not CDK4i, which seems pretty subpar… MDA does have a trial with a CDK4i, CDK2i and Camizestrant, but that's the only trial I've seen where an oral SERD was included.
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Thank you @cure-ious … I'm going with your suggestion and will stay on the Bria-IMT.
My tumor markers are very accurate that's why I'm freaked out, but it's only three more weeks. Hopefully, one of the other trials will have something open sooner rather than later. It's possible I could be waiting for a few months (opening plus screening, etc.) for something different—that's what's freaking me out, too.
But I'll stick it out and see what the scans say on December 29th.
Thanks for the input—your knowledge is so so appreciated!
CBL
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So hard to know, and the mind goes into so many rumination's that it is hard to remain calm and concentrated. I would take a pause, take a breathe and stop. Breathe, observe, and then proceed. Do this for awhile, so you can be at peace if possible with your thoughts. And then ponder your options and the recommendations . From my perspective, I agree with @cure-ious . Follow your MOs advice. We enlist our medical team for their expertise, and in that we trust as best as we can. ❤️
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bits of good news trickling out of SABCS:
New oral CERAN/SERD Palazestrant (OP-1250) plus ribociclib reporting 81% stable or better for at least 6 months for ESR1 mutant MBC, tho lower but still great at 70% for those without ESR1 mutations and 68% for those previously treated with CDK4,6i; ORR (tumors shrinking) was 27%. Longest individual response thus far is 18 months. Overall PFS has not even been reached yet, they are going into phase 3 next year (OPERA-02 trial).
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for those with Her2-positive cancers after taking Enhertu, ALX Oncology showed that a combination of CD47 immunotherapy (Evorpacept) plus a Her2-specific monoclonal antibody gave 55.6% response rate and PFS 7.4 months.
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Holy wow, that OPERA-02 sounds awesome! There are two centers nearby offering it, but no prior metastatic chemotherapy is allowed, so I don't qualify. But great news for those who do. Thanks for the update on both trials.
@rlschaller Thanks, Rhonda. Peace is hard to come by these days, haha, but I'm comfortable with my decision to stay on Bria-IMT for a few more weeks to wait for a better trial. The CDK2 had potential vision side effects that made me nervous, too. That might be a common thing with these trials, I don't know, but they required an eye baseline exam, and they checked it every month, which made me think they're more worried about it than I'd like.
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Opera-2 does sound great, but for those resistant to CDK4,6i there needs to be a CDK2i also in the mix. CDK2i come with a lot more side effects( as some here described them in earlier stages) but this trial sounds like it worked really well for those who are really endocrine-resistant, including those with ESR1 and PI3KCA mutations:
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These are articles about the CDK2i trial I was offered. I turned it down to stay on Bria-IMT per doctor's recommendation, and because there is a vision risk I'm not crazy about, but they're a presenter at SABCS and it was purchased for 1.3B, so there must be something to it.
BeiGene offers up $1.3B in biobucks for preclinical cancer drug
I'm okay with my decision and it's only a few more weeks. But instead of being totally off the table it's still hanging on by a thread. I figure no one coughs up 1.3B for nothing, but the eye thing is a big deterrent. Will need more info on that for sure. Let's hope something amazing comes up for all of us soon!
CBL
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Thanks, CBL, I noticed he did not go in to the side effects, nor how many people had to discontinue or reduce dose, and he strangely did not say what the "endocrine therapy" was that they used. I think this trial may be over now and we will see where they go with new trials?
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The trial Dr Yap discusses above is with the Pfizer drugs:
The trial population was heavily pretreated; all had received prior CDK4/6 inhibitors, and 81% had previously received Faslodex.
Among 18 evaluable patients with HR-positive, HER2-negative breast cancer there were five partial responses. They got a 28% ORR, and side effects were 30% neutropenia.
I didn't see anything about visual disturbances, is that something they said happens with the Beigene drug? Because that drug has only been in patients for a few months…
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Dear all, practice changing results were announced in SABCS for ER+/HER2+ MBC 1st line maintenance with HP/palbocyclib, data from Patina trial: PFS of… 44 months! Wow… We slowly are… GETTING THERE! Great news, as I think last year's SABCS was a bit more boring…
Saulius
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@cure-ious I think I read somewhere that because it was more targeted, the side effects were reduced from other CDK2s, and from the information I received it's Fulvestrant. But I will pay more attention to those two factors and for future research and confirm.
I also recently read somewhere that the TTX-MC138 trial I am so eager to be on isn't giving therapeutic doses which makes no sense. If it's not therapeutic, then what are they testing for? The delivery system only and not the conjugate? I need to clarify with the medical staff before I sign up for it should it become available. And this time bring the actual article with me to the appointment (which means I need to find it again because I forgot to bookmark it. :/)
CBL
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BSandra, This trial is with ER-positive, Her2-positive right? Wow, wow, wow!!! We know that Her2-positive cancers will be the first to see "cures" and, as seen with other cancers, before that happens there will be treatments that give very long remissions, clearly we are already there!
I wonder if some of the newer CDK2/4 inhibitors could be combined with Enhertu for ER-positive, Her2-low and do even better than they already do?
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CBL, Sometimes trials start low but move to higher doses after just a few patients, but even so, in the preclinical work, the effect of TTX-MC138 was strongest when it was combined with chemo, so we don't know yet what kind of monotherapy activity it would have in humans, clearly its still in early stages. This is a very small phase one trial, right? So maybe they are being cautious, giving low dose to make sure it is safe and see what kinds of SEs they are going to be dealing with? It is first-in-class kind of drug, they may not know what to expect or look for- in general though, an RNA antagomir you would think is quite specific.. But I agree, I wouldn't want to try a drug they are not yet testing at what they predict would be an effective dose.
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Yup, very small phase one…like 20 patients. They haven't announced that they've dosed the second cohort yet—last I heard, the no one had dropped out of the first cohort. I didn't recall it being paired with chemo, so that's another thing…
Jumping on too early might not be a good idea if I can get on the CDK12/13 or Aurora A trials first, but waiting for phase 1b or 2 might not be a good idea either. I'll have to freak out about it when the opportunity comes up.
CBL
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this group is quite careful, they did a phase 0 last year to label and track where TTX-MC138 goes in the body, and confirmed it gets into the liver and everywhere it would need to go- this is the kind of thing they have to do when this type of therapy has never been tested by anyone before. Maybe by now they have started expansion and increased the dose. For sure find out the experience of people who did get it
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