Are you currently (or have you been) in a Clinical Trial?
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Hi KarPC
Congrats for moving forward in a trial! I would have loved to try the trial you mentioned. I have the ESR1 mutation and am most likely resistant to AI and Fulvestrant. FYI- I progressed the least while on envirolimus and found it to be tolerable.
https://cancerres.aacrjournals.org/content/80/16_Supplement/5674“In several patient-derived and cell line xenograft models, including models with clinically relevant ESR1 mutations, AZD9833 completely suppresses tumor growth and gives equivalent pharmacodynamic activity to supra-clinical levels of fulvestrant.“
The way I understand it is, because fulvestrant is an intra-muscular injection, The med is not absorbed as well as an oral. So the new drug being tested sounds like it is stronger.
2 questions I would consider. Do you have the ESR1 mutation and what percentage are you ER positive?
I am 100% ER positive and have the ESR1 mutation. The clinic wanted to put me in a serd trial for those reasons but one was closed, another said no to my IVIG drug and for a couple I already had too many treatments.
That is another thing to consider to enter trials - number of lines of treatment are low for many of them.
Sounds like you have an important decision. I hope your next line stops progression whatever you choose
Dee
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CDK 2/4/6 trial report
I found out Tuesday afternoon that I got final approval. Biopsy Wednesday afternoon and first med Thursday with all day blood draws (pk’s)
After a very rough couple of sickly days ( I listed my saga over on the liver mets thread)
my day 2 symptoms are: slightly light headed and having sweaty hot flashes along with some pins and needles. I am also weak but could be still recovering from the events of the last 2 days.
SCRI portal is great so far. I got an immediate response from the team about reporting my dizziness.I am hopeful to proceed ahead. It is nice to have weekly visits to check on my stats and give Pk’s. Tumor marker at week 4, scans at week 8. If there is any progression such as new tumors then I am off the study, but if there is only very slight progression of current tumors then I can stay on longer. So unless I cannot tolerate the side effects, then I have 8 weeks to go.
Dee
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Dee, Do you take the CDK2,4,6 pill continuously? What dose are they giving you? On Ibrance, I had much stronger fatigue at the start but that leveled out after 1-2 months, so whatever side effects do appear might lessen as you continue along
Also, did you say that they had seen stable responses but not tumors shrinking thus far? Do you know if that was from trials that did not include an estrogen inhibitor?
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Cure-ious
I take CDK 2/4/6 twice a day continuously- no break like ibrance. I am on 25 mg /pill. The highest trial dose was 50mg/pill twice a day and there was a death. they had too many adverse reactions at 35mg/pill twice a day. So my dose is now the highest dose and I will stay on it the whole time unless they recommend a dose reduction to combat side effects.
The hormone blocking arms have not started butare about to open if anyone is interested. There is also going to be an arm where someone will get time released ( not sure about how that one will work)
It is hard to get info out of the team, but piecing it all together, there is only stable disease substantiated for those who have stayed on the trial. I think there were 2 cases of partial response but it was unconfirmed. I get the idea that out of the 50+ patients on the study there have been many drop out. MDACC said 40% of their patients get alopecia. 😢
Dee
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So I remember Frisky had also twice a day, which must have been the 50mg pills, and she had to fast before due to nausea/vomiting, also extreme fatigue and mental clarity issues. Clearly the drugs are much stronger than Ibrance because you are only getting 50mg per day (whereas Ibrance is 75-125mg per day, without a CDK2 component). So you will be determining if the amount is still too high, and this is all without an anti-estrogen component added in.
Surely its going to town on the cancer, am hoping SEs are tolerable. Alopecia is disappointing, is that hair thinning or complete hair loss. Many have gotten thinning hair from the I-F, wonder if this is the same deal or more significant..
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Susan, Cure-ious, and Dee - thank you so much for the helpful points to consider. It sounds valid to wonder why an oral SERD would be effective after progressing on Faslodex. My recent guardant360 blood test showed no mutations. I have not been able to get a biopsy since my diagnosis 32 months ago. I was initially 90% Er positive, PR and Her2 negative. At diagnosis, I had my only liver tumor ablated and my liver is currently tumor free. I have many small lung nodules all under 1cm except for one. The largest has grown from 4mm to 1.3cm. It is the only tumor large enough to biopsy but no one will touch it. My second opinion onc and the trial onc also agreed with my regular onc that it would not be safe to biopsy. It may be due to the location in my lung or the size. I was told my guardant blood test may not have showed any mutations because of low volume disease and low levels of ctDNA. Thus, without a recent biopsy or a good sample for the guardant test, I am lacking the info needed to make the best decision.
Dee, I've been following your trial searches. I am hopeful you found a good trial. It's a scary step tho.
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I'm looking for data about taking an oral SERD after Faslodex. With the AZD9833 (oral SERD) study I am considering, as of January of 2020, 60 heavily pretreated populations (53% had received prior treatment with faslodex and 50% had received prior treatment with CDK4/6 inhibitors) saw an overall response rate of 16% and a clinical benefit rate of 42% from taking AZD9833 alone. I am not good at deciphering studies and results, so I don't know if this sounds good.
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Hi everyone,
I have been following along and learning most of this year. It's Thanksgiving weekend here in Canada, so a good time to chime in and thank you all.
The weekly Taxol worked for me for 9ish months after I crashed out of my last clinical trial. A timely dose reduction earlier this year helped minimize the side effects. But August's scan wasn't so good - progression in the pericardium, which I admit spooks me a lot.
Fortunately, clinical trials have opened back up in Canada, and my local oncologist had a couple of suggestions. So I started a Phase 1 trial for a TTK inhibitor, single agent, 2 weeks ago. So far so good. Some pain, but really that's probably referred pain from the mets.
I've thought the CDK2/4/6 trial seemed really interesting, but with the border closed and general travel restrictions, right now I'm grateful that I don't have to travel to a clinical trial like I have previously.
Thanks again to everyone for sharing your experiences. It helps alot.
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Hi, NewGardener. Do you have ILC?
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KarPC- I think that overall response rate (ORR) refers to the proportion of patients who have a partial or complete response to therapy (meaning that tumor shrunk or disappeared) but does not include those who had stable disease. Clinical benefit rate might be the same as the disease control rate?, which indicates everybody who had either shrinking or stable disease. Tumor shrinking is due to cancer cells being killed, and I don't think you would expect that to be high in this trial because anti-estrogens mostly just arrest tumor cell growth rather than kill them off (tho some arrested cells will also die off, of course ). Therefore you would expect the clinical benefit rate to be the higher number, and 42% seems pretty good? when you consider that this is testing the SERD as monotherapy and on patients who had already been on anti-estrogen treatments. But the question is how durable was the response, ie, what was the PFS or duration of response (DOR), how long did it last?
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New Gardener, I think this may be the trial that Weareonthecusp took, you might want to send her a PM.. Here were some links posted from that time:
Review paper on TTK inhibitors: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC53733...
Aggressive cancers with active beta-catenin (Wnt signaling) are five times more sensitive to this drug https://mct.aacrjournals.org/content/molcanther/16...
Weareonthecusp has TNBC but TTK inhibitos are obviously also indicated to work on ER-positive cancers that have become resistant to CDK4,6 inhibitors: https://www.pharmacytimes.com/conferences/san-anto...0 -
Weareonthe cusp: How is it going?! We didn't hear from you for awhile- I hope you are doing well on your current treatment (Xeloda?) and are planning to try one of the ADCs (Enhertu, Trodelvy)...
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Hi Curious, thanks for asking about me. I have actually had a few rough months. I started the xeloda but was continuing to have worse shortness of breath. I went to local hospital a couple times.to get checked but no plueral effusion. Last time I went they did find I had a infection and progression so I stayed 10 days had Antibiotics and 5 doses of radiation to try and calm symptoms. Both so far have helped.. I am not sure what next steps are as of yet. They like to wait a couple weeks after rads to start treatment back up. It will most likely be an iv Chemo.
My oncologist did inquire about Leronlimab and the compassionate use was on hold due to dosage amounts, but was most definitely being given to Canadians. I am very excited about this drug. We will have to keep inquiring about that.
I am really hoping trials start to open up fully soon here. They have not at my cancer center.
The drugs you mention are not available in Canada at this time. Hopefully soon.
I do recall doing a trial with a ttk inhibitor but unfortunately it did not have any effect on me. I dont recall any side effects of any kind if that helps.
Kathy xox
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Curious - thank you for the link to the articles. The trial I'm in did just add a ER+ cohort specifically for the ttk inhibitor and fulvestrant, but because I've had fulvestrant 2x, I'm still in the "all comers" cohort.
ShetlandPony - the original breast tumours were plain old vanilla invasive ductal. My mets have mostly been to the usual places - pleura, mediastinal nodes, liver, but the pericardium is a bit unusual.
weareonthecusp - thank you for the update. I looked back at your last trial description - very interesting to have shots directly to the tumour. I am sorry the response wasn't more durable. I went to Princess Margaret for a pik3ca inhibitor trial back in 2018-2019 and also a short lived (for me) CDK7 inhibitor trial. Good luck with your next treatment. And hopefully some sort of access to Enhertu, Trodelvy will be possible sooner rather than later in Canada for those who need it. The gap between the U.S. and Canada is so frustrating (understatement) - I had to travel to the U.S. in 2015 for a clinical trial to get access to Ibrance because it wasn't in Canada yet.
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Kathy- I'm sorry you are having a tough time! I had to look that drug up again, but I agree it looks really exciting! Leronlimab is a CCR5 monoclonal antibody that both works against metastatic cancer and also boosts immune system killing- interestingly, the company filed in January for FDA Breakthrough designation owing to the results they got with their very first phase 1 TNBC patient (treated Sept 2019) who saw 25% shrinkage plus a Her2 patient who also got a strong response. They also think this drug is going to have great effects on people with autoimmune diseases, so there's an added benefit for those folks!
https://www.targetedonc.com/view/leronlimab-moving...
Would you be getting the drug alone or with chemo?
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PS Here is data from their third patient, just as exciting as the first.
https://d1io3yog0oux5.cloudfront.net/_813c4c1a8684...
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PPS The phase 3 Trodelvy trial for TNBC is wrapping things up and no longer recruiting, and they had several trials sites in Canada, so presumably this drug will be on the market there very shortly. They reported a 35% response rate, some of which were complete responses (shrinking of all tumors) and 45% clinical benefit response (including stable responses) compared to chemo alone, with 5% and 9% response in those categories.
The Enhertu is for any cancer that has some level of detectable Her2 protein expression, even though not Her2-positive these cancers can be targeted by the drug. For cancers with high Her2 expression the drug had a robust 60% response rate and 97% clinical benefit rate (including stable responses). A phase 3 trial (Destiny-04) is underway to see how strong the response is for Her2-low cancers, and there are sites in Ontario and Quebec.
https://clinicaltrials.gov/ct2/show/NCT03734029
Apparently you have choose between these two, they carry a similar chemo payload so resistance to one would give you resistance to the other one. But they are both great options!! The Trodelvy is for sure an option for you, and the Enhertu would depend on whether or not there is some Her2 in the cancer cells.
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Super interesting about the Leronlimab. There is a trial recruiting in Chicago and San Fran but you have to be chemo naive in the metastatic setting so newbies only https://clinicaltrials.gov/ct2/show/NCT03838367
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Hey, but also check out this trial for Leronlimab that started in March for compassionate use- you have to be TNBC, and have had at least three chemos plus a checkpoint inhibitor. The trial will combine the CCR5 antibody with any "physician choice" of chemo. I've never seen this kind of trial, they don't show locations so presumably they just send the monoclonal to your doctor's office. They say they will test 30 patients but do not give an 'end date' for the trial, so maybe its first come, first served?
https://clinicaltrials.gov/ct2/show/NCT04313075
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Yep, Leronlimab. I follow it for a year now. Third patient account seems even too good to be true. They target CCR5 but in compassionate use study recruit mTNBC only, why? I don't get this, as CCR5 is found on many different BC cells, so why to narrow the set when prelim data shows good responses in HER2+ too? And they still are recruiting after 6 months when they need only 30 people - where are the people? My point is... seems like a breakthrough but things again move so slow:/ Just guessing... recently internet became full of articles about CytoDyn's drug Leronlimab and its good results with treating COVID-19. Guess where bigger money is at stake now? Some 50.000 (I just thought of this number myself) people with MBC+CCR5 worldwide a year, or 50.000.000 with COVID...? I just hope I am wrong:/
Saulius
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Saulius,
Yep, the CCR5 protein is needed for Covid and HIV-1 to infect cells, so its safety record is well-established from all the HIV-1 trials and now there is a strong push to get it through Covid trials for emergency use authorization approval from FDA. The anti-cancer studies are much newer, but look so promising. My guess is they limited the compassionate use trial to TNBC because there are more treatments already available for HER2-positive and ER-positive MBCs. It doesn't seem so slow really- many phase 1 trials only have 30 or so patients and they take 3-5 years. One perpetual problem is getting enough publicity to accrue eligible patients for the trial, plus this one has been going on during Covid. The trial only has been going on for a few months and we don't know how many people have already signed up, but the trial size is probably the minimum needed to get an indication of whether Leronlimab can be useful for heavily-treated patients. It would be great if they made a larger trial to include all MBC patients, CCR5 expression is common in cancer and it has this secondary effect on the immune system, so two ways it can treat cancer.
there is a video link here about the role of ccr5 in immunooncology
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Dear Cureious, I hope it is as you say, as we need effective treatments and we need them today, not in 10 years... Saulius
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Cure-ious,
Thanks for posting the video link. Although I didn't understand the whole thing (too many acronyms being tossed around that I can't keep straight) I found it very interesting to view.
If the safety profiles are already done with respect to HIV, can that somehow speed up the process for use with cancer? Or must the company do the same extensive testing on MBC again?
As Saulius said, we need this stuff sooner rather than later.
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Thanks Cure-ious for helping me understand the trial info.
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BevJen, I guess they are doing the compassionate use trial because the only other way to get the drug is through the trial Moth listed for firstline treatment (which shows how confident they are in the drug). As Saulius says why not do trials for all cancers that have CCR5 expression, which could be because this company cannot move that fast because they are not one of the big pharmas, and/or there could be other trials going on or planned, as the third patient report said they already had a lot of people who want it and were in talks with the FDA...
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I found another basket trial for all solid tumors expressing CCR5 with Leronlimab: https://clinicaltrials.gov/ct2/show/NCT04504942?term=leronlimab&draw=2&rank=1. Maybe this is what we want... Saulius
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Saulius,
Thanks for posting. Sadly, it's a single site trial in California. Perhaps they will expand at some point. I hope so.
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I am hoping for the KEYLINK 007 trial once I get my brain radiated. It’s to target Homologous Repair Deficiency (like my PALB2 cluster F) and add in Immunotherapy.
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CDK 2/4/6 week2
Bloodwork looks decent, only new thing was a slight dip in HGB. Painful swallowing resolved. No hair thinning yet.🤞🏻
The NP says my side effects of flank pain on the left is not associated with any known trial SE. We did trace back to me moving a couch and that could be the cause of it. She looked at that side on the ct from 2 weeks ago and did not see anything. she offered another CT scan but we settled on trying some muscle relaxers.
It stinks that I feel like crap due to the migraines and burning flank pain. I just want to feel like my old self. My husband is so wonderful but all this is wearing on him too. He is worried for me.
Dee
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Saulius, Thanks for posting that! Another odd duck trial. Only at one San Francisco site for now, however it just started like a month ago and might intend to add sites? Phase two, for any solid tumors with CCR5 expression, but limited to only 30 patients?- even odder still, they say it will only run through next year. They may be wanting to check something specific out, before moving to a larger trial?
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