Are you currently (or have you been) in a Clinical Trial?
Comments
-
Draft guidance usually means it is going out for consultation to industry/academia/etc for comment and for concerns to be raised and analysis challenged before a final decision/proposal/policy is made. This one has a consultation period of 60 days (pretty quick actually, that is impressive), and then the agency will need to page through the responses and amend the guidance into final either on its own or part of a broader policy change. Maybe 6-9 months to final guidance? Totally guessing but based on my experience and the fact that the FDA has accelerated policy pathways already established, it could go that fast.
0 -
This sounds encouraging. It seems like clinical trials want us to be identical mice when they exclude people who have had other treatments. A lot of people get left out. Do other clinical trials practice this?
0 -
This is exciting, Sondra, thanks for all your insight! I guess since we can ask for compassionate use anyway, this is just streamlining the opening up of the process. The pharmas probably won't be thrilled because they like to cherry-pick their cohort, but perhaps they won't have to report on the results of patients who took their drug but did not fit their eligibility criteria?
BlueGirl- NCI has pretty much all the clinical trials, they are the only game in town
0 -
So it seems that I am having an allergic reaction to tomivosertib. I complained to the trial RN about an itchy horrible rash last week & she told me it's not a SE of the trial drug so it must be something else. I told her the rash intensifies within an hour of the 2x daily dosage. After 5 excruciating nights of relentless itching I stopped taking the drug, rash was completely gone within 24 hours. I guess if they say it's not a SE then it must be an allergy?
They want me to restart the drug tomorrow on ½ dosage. We are in the midst of an unprecedented heat wave where few have air conditioning because most summer days are 24c (75F) it will be 40C (105F) for the next few days. I can't imagine trying to live with an intense rash & itching while living under this intense heat. Sometimes I wonder if I'm crazy to be doing these trials with their crazy rules.
0 -
GG27- You are dealing with so much- sleep deprivation, anxiety, pain, and a trial nurse who does not seem to care about your condition. Can they give you benedryl and/or a steroid to premed? That rash sounds horrible.
I had a rough time with stomach issues on my first trial. My team was responsive with meds to help treat it. I hope you can talk to your team again and get help.
Dee
0 -
KarPC, thanks for posting about the FDA draft guidance - that is very encouraging, and if implemented, I think it would be a welcome change to the clinical trial world.
GG27, I'm frustrated for you! Why are they not acknowledging that your rash as probably from the trial drug? It just seems like in a clinical trial setting, they should really not be so dismissive of a reaction like this. Can you talk directly to the trial doctor? I hope things get better for you. I hope the heatwave breaks soon too.
0 -
Thanks Dee (from the other Dee) and Buttonsmachine.
I see the trial RN & MO tomorrow. It's not so much that the trial RN doesn't believe me but that the trial is telling her that it's not a SE. I have clearly proven that it is caused by the trial drug, I don't really know what they would call it. I ended up on the last night I took the trial drug. taking 4 Benedryl through the night with it having almost zero effect on the rash or itchiness without the SE of sleepiness. I have found this is one of the problems of being one of the first participants of being on a new trial. I had the same problem on Alpelisib, having SE's which the trial wouldn't allow to be mitigated and I had to leave the trial due to grade 3 SE's
I do get intravenous benedryl and steroids prior to chemo which hasn't helped as I've had an anaphylatic reaction both times, so I'm a little on edge restarting the trial drug tomorrow and then chemo on Tuesday.
My MO is great so I hope she has a new plan for me. I am running out of options I'm afraid, I've been at this for 7+ years and have had a few things not work for me.
I just checked the latest weather forecast, they've upped it to 44C / 111F supposedly to feel like 50C / 122F, oh dear gawd, I don't know how we will survive this.
I will post how I get on later in the week. cheers, dee
0 -
Hi Dee!! Hopefully the half dose fixes that rash problem! As for other drugs, have you tried Verzenio on its own, or a PARP inhibitor, or Enhertu/Trodelvy?
0 -
KarPC - Thanks for posting that FDA draft! This would open so many more trials! Does anyone know if this document is open for public comment also? If so, we should be writing in support of how it would benefit us.
0 -
GG27 is it the case that the trial people would rather have you leave the trial than acknowledge the rash SE and help you with it so you can stay on?
0 -
Cure-ious, I just checked and none of them are funded by BC Cancer, but I will ask my MO as she is really good about nagging drug co's to fund drugs to patients.
ShetlandPony, I'm not sure what the problem is with the trial people, I will find out the whole story tomorrow when I get together with the trial RN & my MO, but that seems to be part of the problem, they allow absolutely no wiggle room. For example, I have to travel 5 hours each way to the trial centre, now that's fine for trial stuff but they will not allow me to have the paclitaxel part of the trial at my hospital even though there is nothing special or different in the way it's administered. They have just decided that it's their way or the highway. My MO has said "in this day & age of online everything, if the chemo RN takes a picture of Dee having the infusion shouldn't that be ok?" No they replied it must be done in Vancouver.
And the irony is that they are having a hard time finding participants because of the rigorous preliminary stuff such as 2 liver biopsies 2 weeks apart, PK's done every 2 hours over 36 hours. I hate to give up a line of treatment but I'm starting to have my doubts. thanks all, I'll keep you posted. cheers, dee
0 -
Hmm. I had a difficult start on my trial, with so much diarrhea and vomiting that I became bedridden and had to go to the ER for fluids and electrolytes. I found out quite a while later that the trial people (pharmaceutical company) wanted to kick me off but my onc fought for me. Were they afraid I would make their drug look bad? Now (after two more starts with more SE meds and a dose reduction) I am making their drug look good, as the patient with the longest pfs on this trial so far at my cancer center (16 months).
I really hope they will work with you. Do they want trial participants or don't they? Sheesh.
0 -
GG, trodelvy isn't approved in Canada yet. I keep hearing it will be any day - rumors are sometime this summer. And then after approval will be the separate issue of whether bc cancer will fund it.
0 -
ShetlandPony-that's fantastic 16 months! And you have had to persevere through so much
GG27- it's fun we share the same name. I hope you get through this rough patch. Your MO sounds like he/ shewill be a good advocate.
I just had my trial checkup and Dr Hamilton said we are hoping for large double digits I am half way through cycle 7
Dee
0 -
Dee, What does large double digits refer to?
GG-Dee, Precisely, the trial system needs to be amended- they are always whining only 6% of patients take a trial, but then they put in all these restrictions. I'm hoping these new guidelines from FDA open up all trials, because faster accrual will give us not only better and easier access but also faster results. We are reasonable patients, and they are not going to get better results out there in the "real world" if they want to ignore something as common as therapy-induced rash
SP- Congratulations- 16 months!!!! That's so great
0 -
Cureious - I’m on cycle 7 so hoping for cycle 37 and beyond 🚀
😉
Dee
0 -
I'm being screened for the PACT Pharma trial. They took blood and tumor samples months ago. I was just informed that the researchers will be "able to make a 3 TCR product, that is 3 distinct T cell clones targeting 3 distinct tumor neoantigens." This is a very personalized trial with high risk and high potential reward. Does anyone else have any information on this trial?
GG27 - I hope that you will get answers today. An oncology dermatologist told me that zyrtec can sometimes work best with rashes caused by cancer treatments (like piqray). Can you ask your trial doctor about trying something in addition to Benadryl?
AlabamaDee - Glad that your checkup went well at that Dr Hamilton is optimistic that you will get a long run on the trial!!
0 -
Theresa...what is the NCI number?? I can't even find anything with the words PACT or TCR3
0 -
teresa45 - is this that Phase 1a/b trial? Just reading some of the background info on this - sounds like next gen level gene editing stuff! What do they say some of the risks are?
Each person's cancer emerges with a private signature of mutations. PACT Pharma identifies these cancer mutation targets (neoantigens) for each person, biochemically verifies and captures T cells from their blood and uses its proprietary, cutting edge (non-viral) precision genome engineering technologies to manufacture a personalized immune cell therapy product for each person with cancer
Nicole - here is an older article but may give you some leads:
https://medcitynews.com/2019/07/pact-pharma-enroll...
Edit: think this is the study info:
https://clinicaltrials.gov/ct2/show/NCT03970382
0 -
Thank you Sondra...
0 -
Theresa45 - that sounds like a great trial. I hope you get in and that it kicks the cancer! It appears to be similar to car-t therapy but targets the protein and it’s personalized!
FYI- my drug is a different technology but also targets the protein (PROTAC technology)
Keep us informed!
Dee
0 -
GG27 ~ So sorry to hear about what you are going through. My Oncologist tells me that many of my side effects are not side effects of the drug I happen to be on. We have a long history of this game and it drives me crazy. I go on this amazing forum and read how others have the same side effects that I have. I usually get nasty rashes at the start of each new drug. I found that Triamcinolone Acetonide Cream SUP .1% works most of the time - I asked for a big jar of it.
Shetland Pony ~ What a wonderful success you've had on your trial. So glad you are able to handle the initial side effects.
Theresa ~ The personalized aspect of the trial sounds promising.
0 -
Ooh, ooh, ooh, Teresa, the PACT trial!! I sent them an email about a month but got no reply- not urgent since I do not know if I am responding to current treatment, but I wondered if they were at a point where they would target more than one neoantigen, because at the start of the trial they only were going for a single antigen. This is pretty much what Judy Perkins did, right?! I am so excited to hear they are moving forward, please keep us informed. So, you would get the TCR infusion, and then what, do you just get it and move forward with whatever the next step is, or do they keep you in the trial to see if it works and just take it as monotherapy?
Dee- Hell, yeah, keep going!!!
0 -
Returning to the subject of enobosarm, it appears to be working on my wife. She reduced her verzenio dosage by 33% and started taking 9 mg enobosarm daily 2 months ago. Her scans show stability, and her tumor markers, CEA and CA-15 dropped 30 and 40 percent.
0 -
https://clinicaltrials.gov/ct2/show/NCT04505826
Has anyone been on this trial? It’s a new class of drug called “complete estrogen receptor antagonist” or CERAN. Not sure how different this is from a SERD, but my second opinion MO from a large cancer center highly recommended it and said they’ve seen good results so far. Does any one have any info about CERAN?
0 -
Thanks for the congratulations and words of encouragement in response to my trial success.
Husband11, I'm so glad to hear this good news about your wife's response to enobosarm. I've noted your post for future reference.
Figtree, I was watching the ILC Symposium earlier this week, and it was mentioned that tamoxifen is an estrogen antagonist and partial agonist, meaning that is can both block and promote estrogen. (The idea under discussion was that a partial agonist may not work well for ILC.) Faslodex is simply an estrogen antagonist. Is CERAN one of the new oral SERDs? Maybe they mean it is just antagonist. Someone said that the earlier generation of oral SERDS being worked on were both, but that the newer ones are only antagonist, so ILC patients would not need to worry about that. Someone please correct me if I am not making sense, but this is what I understood.
Edit: Oh, I see from a quick search that CERAN is an acronym for Complete Estrogen Receptor Antagonist.
0 -
This disconnect between trial folks and patients is so unfortunate. We need each other. They would be wise to solicit the patient perspective, and everyone would win.
0 -
I wonder if "Complete" means it blocks all estrogen receptors, in all places. No estrogenic properties whatsoever. As Shetland mentioned, some drugs like tamoxifen will act as an antagonist (blocker) in some sites, and act as an agonist (activator) in other sites.
0 -
Fig- I was wondering what CERANs are as well. Below I edited an explanation from the company, hope this is clear.
There are two different sites of the ER protein that can turn on genes, called AF1 and AF2. AF2 responds to estrogen, but AF1 can be activated by other signaling pathways, and the AF1 site allows ER to turn on genes independently of estrogen, which can cause endocrine resistance. Selective estrogen receptor modulators (SERMs) like tamoxifen efficiently shut off the AF2 site, which is turned on by estradiol, but they do not completely shut off the AF1 site. Fulvestrant and other Selective Estrogen Receptor Degrader (SERDs), including AZD9496 and GDC-0810 also do not block AF1 activity when the ER protein is regulating a gene. The signaling pathways that can use the ER AF1 domain are mediated by SRC family kinases, IGFs, and FGFs. Therefore, it is speculated that the SERM-type SERDs are not as good in treating resistance compared to CERAN-type SERDs.
The CERAN/SERD OP-1250 completely blocks both AF2 and AF1 activity in cell culture. OP-1250 is also active in a large variety of cell lines, including those in which some SERM-type SERDs have little activity. OP-1250 achieves high and stable drug exposure in multiple animal species, unlike fulvestrant and many SERMs. As might be expected for a compound with this spectrum of activities, OP-1250 shrinks tumors in xenograft models in which fulvestrant and SERM/SERDs fail to shrink the tumors. These results suggest that OP-1250 has potential to be a superior compound to treat ER+ MBC, especially in patients whose tumors allow high activity of AF1 and including those with activating mutations in ESR1.
PS I think the reason it has taken so long to get a SERD to clinic is because pharma did not realize at the beginning that they needed the drug to both inhibit the activity of both sites on the ER, AND degrade the free protein. They thought Faslodex just worked by degrading ER, later realized it also inhibits, and then also discovered two sites need to be inhibited. The reason you need to inhibit ER and also degrade it is that the ER never gets completely degraded (Faslodex brings it down to about half the normal level in six months) and the stuff that is already bound to the DNA turning on a gene is resistant to degradation, so to block that you need to inhibit its activity. So, technically, the CERAN-type SERDs ought to be the best.
ARV-471 says they may be the best in class because they degrade the ER by 90% (compared to 50% for Faslodex), but I don't know how well its ER inhibitory properties are relative to CERAN-SERDs. And maybe one will work even after resistance develops to the other...
0 -
Oh, I see. We are talking about more than just antagonist and agonist activity. It is about different sites on the estrogen receptor. So just as faslodex can work when a cancer is resistant to tamoxifen, a CERAN might work if Faslodex fails. Maybe it will extend the time endocrine therapy will work, and maybe it will work better for ILC in general. Taking more notes!
0
