November 11, 2018 at 7:23 am #97750
High dose vitamin C injection has given very good results against Kras mutation. most pancreatic cancer has KRAS mutation. there is a trial going on vit C-pancreatic cancer (KRAS) theraphy. pls check out.
”There is a trial going on at Weil Cornell using vitamin C. I think it is for people with certain KRAS mutations and maybe also for people with BRAF mutations. Unfortunately, it is for pancreatic cancer only.”October 19, 2018 at 11:03 am #97678
We are patients and caregivers in this community, so regretfully are not in a position to offer medical advice or interpret medical information.
Regarding your questions, here is what I have observed among folks reporting on this board. Most, but not all, of the targeted trials right now for cholangiocarcinoma relate to the FGFR and IDH mutations. We also have patients who participate in solid tumor trials or who are prescribed off-label treatments relating to genomic defects that are rare for cholangiocarcinoma but common for other cancers. An example of this is the HER-2 mutation common for breast cancer but rare for cholangiocarcinoma. And as you note, cholangiocarcinoma patients with MSI/MMR/Lynch syndrome defects (this is a very small percentage of our patients) are candidates for immunotherapy treatments such as Keytruda that have shown some effectiveness for this group.
So what should a patient do if the genomic profiling report does not show mutations in the categories above? Looking at what our patients and caregivers have reported, I would summarize as follows:
1. There are many trials to look at for treatments that do not require specific genomic defects. Some trials are about chemo drugs, while others may involve liver-directed treatments such as hepatic pumps, ablation or TACE. Some involve radiation. Some trials combine two or more categories of treatment. There is a welter of information on clinical trials.gov. It takes careful searching through this database to find information relevant to a specific patient on what treatments are being developed and tested.
2. In a search, start with “cholangiocarcinoma,” “liver,” and “biliary.” A larger category that can also be searched is “solid tumor.” You can focus on trials that are geographically accessible.
3. Also search any mutations that have come up in testing.
4. If you find promising trials for which the patient seems to meet the inclusion criteria, a next step would be to bring them to your doctors’ attention. You could also call or write to the indicated point of contact to explore if the trial is a viable option.
One challenge with a rare illness is caregivers and patients end up doing a lot of their own research. The resources on this website should be helpful in identifying potential treatments. Searching on the discussion board will help you locate patient experiences with the different treatments.
I hope this is helpful.
Regards, MaryOctober 19, 2018 at 3:54 am #97676
Thank you Mary
What I ve understood from foundation one results and immuno drugs , in principle
they are checking seperately 3 main things:
1- gene mutations and its quantitty so that to understand if the reason/main cause of the cancer is gene mutations?
2- capability of repairements of DNA (MS)
3- if tumor tissue has PLD1 protein (which stops immune system to recognize if it is a tumor)
in my understanding researchers mostly have developed drugs for patients whose tumor has PLD protein. Thats why pld1 negative people (like my mom) are not a good candidate for approved drugs. So I have to search for drugs/trials working on MS stabled and gene mutated patients ? am I correct?
October 19, 2018 at 2:33 am #97675
- This reply was modified 1 year, 9 months ago by Bgulmus.
my mom is 68.
PD-L1 Tumor proportion score TPS % 0
KRAS amplification-equivocal, G12R
KMT2C (MLL3) deletion exons 4-40
TMB-Low; 3 muts/MB
I attached other gene mutations.October 19, 2018 at 2:26 am #97674
Lili, No stop! it was a trial! keep looking for another trial. as long as your father is emotionallly and physically eligible, you have to keep searching. We all know still there is no certain cure for the illness. the goal here is to make them live in good shape with the illness with medicines and treatments! please please have a little break and keep searching.October 18, 2018 at 6:16 pm #97673
As you indicate, for cholangiocarcinoma, using targeted treatments based on genomic profiles is relatively new. Add that to the rarity of our cancer, and we end up having to search around for sound medical advice.
There is a good article this month at nature.com about precision medicine for biliary cancers. You may find some information on the mutations that you listed.
As regards immunotherapy drugs such as Keytruda, my understanding is that for cholangiocarcinoma, when they are administered as single agents, they work best in patients with the relevant genetic defects, e.g. MSI. This is likely why doctors were discouraging on this point after seeing the list of mutations. But, there are also a few interesting trials afoot both for cholangiocarcinoma and for solid tumors that combine immunotherapy with other treatments, under hypotheses that immunotherapy enhances the effectiveness of traditional treatments. I have seen descriptions of trials for immunotherapy combined with chemo, with radiation, with ablation (e.g., the trial Lili’s father participated in) and with TACE. This set of trials may not require patients to have any specific mutations.
I hope your search for treatment options is fruitful.
Regards, MaryOctober 18, 2018 at 9:10 am #97664lilitmParticipant
I wish I knew for sure how to help you ~ I think the reason they are saying it is unlikely immunotherapy will work is because there is low Tumor Mutational Burden and Microsatellite Stability. Did they check for PD-1 or PD-L1 expression? Or any DNA mismatch repair genes? Those are also potential indicators that immunotherapy might work…
What kind of K-ras is it? Ours is K-ras (Q61H) but the NIH has a trial for K-ras G12V I believe… contact Ellen (Dr. Steve Rosenberg’s nurse) at email@example.com and show her your K-ras result and ask if the trial might be a possibility? (I know you would have to travel but maybe she can advise you further?)
I don’t have experience with the other mutations but I would search each of them on clinicaltrials.org. Maybe there is a targeted treatment…
Just found out our immunotherapy trial did not work : ( I am devastated and hoping somehow it will be ok. No idea what is next.
my best wishes to you and your loved familyOctober 18, 2018 at 8:50 am #97662
Hello again Lili, I need help please. we ve received Foundation one results a few days ago. gene based treatment is very new in here and cant make sure if our oncologists can make up-to date comments! I ve talked to 2 oncologists and both of them are saying, “nothing to do with immunotheraphy with your results”. We ve got :
Tumor prop score: % 0
Tumor Mutational burden- Low, 3muts/ Mb
MS – stable
can you comment based on your experience? can you direct me? what to search in clinicaltrials.org?
all the best.
October 16, 2018 at 7:49 pm #97654
- This reply was modified 1 year, 9 months ago by Bgulmus.
Hi Priscilla and Elodie,
Thank you for your note. I am happy to hear that you are finding the Cholangiocarcinoma Foundation’s website resources helpful. I hope your father is doing well with his treatment. Please stay in touch.
Regards, MaryOctober 16, 2018 at 3:16 pm #97653
Thank you Mary for this information. Cholangiocarcinoma Foundation website has been really helpful for us so far. Thank you so much for your time.
Regards, Priscilla & ÉlodieOctober 16, 2018 at 3:14 pm #97652
thank you so much for your message. It gave us a lot of good information and it means a lot to us. We really hope all the best for your father.
Priscilla & ÉlodieOctober 11, 2018 at 6:43 pm #97639lilitmParticipant
dear Priscilla, I’m so sorry for what your father is going through, and you and your sister with him. My dad also has metastases (peritoneal carcinomatosis and perihepatic nodes, and a tumor around the portal vein/bile ducts, which required him to get a plastic stent.)
He does not have any genomic markers for immunotherapy either, but we are on an immunotherapy plus ablation trial at the NIH. It uses anti PD-L1 (durvalumab) and anti CTLA4 (tremelimumab) with one ablation procedure to one tumor (we did it to a perihepatic lesion, in the beginning of August, after 2 months/infusions of the immunotherapy.) The first scan at the end of Aug was stable. I hope that’s a good sign. Our next scan is next week – scared but hoping for good.
The idea behind using ablation with immunotherapy is that the ablation (radiofrequency ablation in our case) releases neoantigens, and the primed immune system would hopefully then recognize the cancer and create an abscopal effect (go after metastases all over.)
Apparently combination immunotherapy (like nivolumab and ipilimumab, or our combo) showed some efficacy for lung or liver cancer patients who did not express PD-1/PD-L1… as far as I know, they don’t have the data yet for biliary cancer.
Sending my hopes and wishes with love, LiliOctober 11, 2018 at 4:11 pm #97637
Welcome to our community. I am sorry to hear about your father’s diagnosis, but thankfully he has the support of you and your sister as he navigates treatment.
My impression of the evidence to date for cholangiocarcinoma is that immunotherapy treatments being tested as single drugs have had better results for patients with the indicated genomic defects (e.g., microsatellite instability, Lynch syndrome), than for patients without them. But this is a question best asked of your oncologist.
There are other trials that pair immunotherapies such as pembrolizumab (Keytruda) with more traditional cancer treatments – these trials may not require patients to have specific genomic defects. I have been trying to read up on the science behind these trials, as a layperson, and in some cases they are testing hypotheses that immunotherapies may boost the effectiveness of traditional treatments such as chemo and radiation. My personal and very much layperson observation is that these combined treatment trials may have an advantage that the new immunotherapies are being provided together with traditional treatments already known to offer possible benefit. A downside might be the more treatments involved in a trial, the greater number of possible side effects that might crop up.
Immunotherapy is a new frontier in cancer treatment, so treatments are not yet mainstream. They are mostly in a testing process through clinical trials, and published studies on their effectiveness are generally for smaller numbers of patients. There is much promise and hope in immunotherapy for cancer patients.
I hope this is helpful. As you find potentially interesting clinical trials for your father to consider, please note that the announcements for trials usually give contact information. It is worthwhile to call or email the trial staff with any questions you may have.
There are great resources for patients and caregivers on the Cholangiocarcinoma Foundation website to help your family on this journey. I hope you will take a look if you have not already done so.
Regards, MaryOctober 9, 2018 at 8:21 pm #97632
Hi everyone. My father has intrahepatic Cholangiocarcinoma with metastases. He is now under chemotherapy. My sister and I are trying to find a trial that could be interesting. My father is MMS and not microsatellite unstable. We read an article saying that some stable patients can also have benefits from anti PD1. Does anyone here receive anti PD1 treatment? Thank you for your help.
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