Search Results for 'AG-120'

Hi Deadlift,
I’m so sorry that you are going thru this. My dad was diagnosed in July after about 6 months of tests,etc. My dad has one large tumor and 5 small ones, all in the bile ducts. You mentioned your wife is in the AG-120 trial. Has she been diagnosed with IDH-1 mutation. My dad has that. He has done two chemo treatments of Gem/Cis, so far.

Anyway, I will be thinking of you and your family. I’m glad that you found this forum. It’s been a huge help to me.

Vallerina

Michelle, thank you for another thoughtful post.

She retired from work a few months after the diagnosis and is essentially homebound due to the nausea. She is physically able to do all her ADLs, but her nausea gets much worse whenever she exerts herself so she ends up not wanting to move. She is fatigued most of the time, but that might also be due to the fact that the only meds she is taking currently are Ativan, and now Marinol.

I absolutely think that her emotional state is contributing, but probably 50%+ of her symptoms are not linked with emotion. Sometimes she is in a decent mood but feels very unwell. When she starts to feel sad there is no question that the symptoms get worse. I think the olanzapine was undoubtedly helping even more due to the antidepressant effect, which is another reason it was too bad we had to stop it. I have tried to get her to start an antidepressant, but she is very insistent that she is not depressed, just nauseated, and it’s hard for me to push too hard.

I certainly agree. We’ve had a few different people think about the nausea, but at the end of the day nobody can come up with a great solution. She had an EGD not that long ago and it was entirely normal, so it seems likely that the nausea is entirely related just to the tumor, possibly from liver distention.

Thanks for the link. I hadn’t seen that group. There are a handful of people on AG-120 doing quite well at DFCI. There have been people on it for more than 20 months with stable disease. There are others who progressed significantly on their first scans. It seems like IDH-1 targeted therapy has huge potential, but they haven’t quite figured out who will respond and who won’t.

I think you’re probably right. The pure THC of Marinol doesn’t seem to be ideal. I’m planning to get her a 50/50 mix of THC/CBD oil from the dispensary. Hopefully it will work.

Mvpratt wrote:

Lastly congratulations on your new baby. That will certainly make your mother feel better…..

Thank you! I am extremely excited to see my mother playing with her granddaughter.

I’m glad you were able to find something that works. I’ve written for Benadryl for patients that receive high doses of narcotics, particularly those with sickle cell disease, to prevent narcotic side-effects, but I’ve never used it for patients with cancer-related nausea. It is certainly an easy thing to try. Thanks for the suggestion.

I also would like to add…. I was unaware that you were a physician so please forgive repetitive information.

I also reviewed your entire thread here and had a few thoughts….bostonguy…..

1) how is here fatigue? for me when I am tired and overwhelmed emotionally or physically it seems my nausea is off the charts? Is she able to go throughout her day or has her activities been affected by the cancer?

2) I can’t say enough that my physical state is really affected by my emotional wellbeing. Could your mother be thinking more about the severity of our diagnosis ( not well cured cancer) in relation to a new grand baby being born? The ebb and flow of emotions is really unbelievable. This could really be a new happy but stressful event for her that may be contributing to the nausea.

3) Is there something maybe in her history/ros that might be getting overlooked. I know that it is so tremendously hard for me to remain in the patient corner when things get more difficult for me… I try very hard not to try and lead my team. Lucky for me I have a great doc who knows me better than myself …lol. Maybe go back to how she is describing the nausea…. or keep a journal to identify if there are any common factors associated with it throughout the day. This could be really helpful.

4) TD is so uncommon…. I know it is a worry with the reglan but you were using olanzapine which causes tons of TD and she never suffered with that side effect. GEM/CIS are great for causing terrible side effects. I am sure you have thought about an emptying study and upper endoscopy.

5) Glad to hear she is not in pain especially in her abdomen. I had to have some pain management due to the cancer returning in L5. really did a number on my leg. I have kept a low dose of narcotic at night .. I do not know her disease burden but sounds like she has been so lucky in that respect

6) WOW are those markers high but acceptable… I am fascinated at the range… there are so many folks like me that their markers never got above 150 and then there are others that have them in the thousands. Clearly though she has some inflammation somewhere… and yes I am glad for the gold standard of imaging…

7) Have you joined the FACEBOOK GROUP for patients on the AG-120 . There is a ton of first hand info on that page. I had considered applying to the trial but keeping up with the postings I have since reconsidered. Here is the site https://www.facebook.com/groups/753847751426566/

The first job I had as an NP was for a neurology practice and marinol was used frequently for severe MS patients. I would think remembering those patients that the CBD oil would work better than the synthetic… Would get your mother maybe to try both and let you know … she might like getting a choice for once… lol This cancer doesn’t allow for tons of choices.

9) I wish I had some great suggestion to help you and your mother. I am sure you will find something…… Also good luck on the rest of the trial. I am very interested to hear how it goes.

Lastly congratulations on your new baby. That will certainly make your mother feel better…..

Warmly,
Michelle

Michelle, thank you for sharing your experience. As a physician, I too know that there is nothing quite like personal experience with disease. Even with all the years of training I had to go through to become a physician, I find myself a much better physician when dealing with illnesses I have direct experience with either with myself or family members.

We tried dronabinol (Marinol – synthetic THC) this evening and it seems to have worked moderately well. It didn’t quite take away the nausea, but she did have a much stronger desire to eat and said she actually enjoyed her meal. Her oncologist wants her to start taking it twice daily for now. If it doesn’t work as well as the CBD we will go back to the medical marijuana (from a dispensary) rather than the Marinol.

I agree that metoclopramide (Reglan) can be a good agent for situations such as this, however I would be worried about the side effects of QT prolongation (as you mentioned) and also tardive dyskinesia. I use it all the time with my own patients, so it’s a bit of a double standard. My mother tends to be very sensitive to side effects, and gets nervous about them, but it’s definitely on the list of drugs to try if nothing else works.

She is currently NOT taking any narcotics. She has not taken a single narcotic since this journey began. Her symptoms are primarily nausea and fatigue. She is only taking the AG-120, which is a tablet, and does not have the same issues that would lead to gastroparesis, but I think that is a very good thought and is always something people in this situation should consider.

We gave acupuncture a try, but unfortunately it wasn’t much help to her. We might give it another try if she is up for it.

Unfortunately, this nausea has been present since day one, prior to any treatment, so I don’t have any expectation for it to be perfectly treated. However, it would be great to get my mom to feel a bit better for a little while, especially with a new granddaughter due in a couple weeks that I’d like her to be able to enjoy.

Michelle, thanks again for your very thoughtful post.

While we are very pleased that AG-120 appears to be keeping the tumors stable, unfortunately her symptoms of primarily nausea are not improving. AG-120 does not shrink tumors much, so we don’t anticipate any improvement in the nausea.

She had been taking olanzapine, started for chemo nausea, which was actually helping a bit. Unfortunately she has some new conduction issues on her EKG, which can be due to olanzapine (and basically all antiemetics), so we had to stop it. The findings were QT prolongation and a new RBBB (right bundle branch block). She had an echo that was normal the same day (though that doesn’t always tell you anything about conduction issues, particularly a RBBB). The EKG issues resolved with cessation of olanzapine. AG-120 may cause QT prolongation according to the consent form, but I think it is more likely due to the olanzapine (or possibly the combination of both).

She gets some relief from lorazepam (Ativan), but it makes her drowsy and I think she is building a tolerance. Things that haven’t worked for the nausea: ondansetron (Zofran) and prochlorperazine (Compazine). She is resistant to trying new things.

Now we need to find something that actually helps her nausea. Against all odds I convinced her to try medical marijuana (a strain that was primarily CBD) and it provided some relief. We’re planning to continue with that if she’ll allow it.

Has anybody here been involved with this trial? I think dasatinib will be the next thing we try for my mother if AG-120 stops working, so I am interested to hear from people who have experience being in this trial. My mother has the IDH-1 mutation, but also has an ABL1 rearrangement (not BCR/ABL, but at the same location), so this gives even more reason to believe dasatinib would be effective.

Just got the CT and PET/CT results. Amazingly, there has been interval decrease or stability in all of the lesions in the liver. There are no new lesions in the liver and there continues to be no metastatic disease anywhere throughout the torso. The PET shows decreased size of several lesions but with similar FDG avidity.

We are obviously very happy with these results. This is the first time that my mother’s CT or PET has shown stable or decreased disease. Every prior scan showed steady progression through gem/cis and FOLFOX.

I’m not sure what to make of the very elevated CA 19-9, but perhaps it is just a sign that the AG-120 is working. It’s a bigger bump than I would expect, but the CT and PET are still the gold standard.

We have not yet met with her oncologist to discuss the results at length. The appointment is tomorrow. I’ll continue to provide updates as they come up.

Marion,

Thank you for your warm wishes. I consider myself very lucky right now to be doing so well.

I am enrolled in the phase II trial of Agios AG-120. Here is a link to the trial:

https://clinicaltrials.gov/ct2/show/NCT02073994

Regarding the transportation discount, I had heard about it through friends.

Thank you very much Marion and Bostonguy — also terrific to hear that initial lab results are looking good. The AG-120 was certainly a positive experience for my mother and wish she could have stayed on it longer. Thanks again and all the best!

Sincerely,
Steven

Steven, so sorry to hear that things have been rough for your mother. If you are unable to get approval for other clinical trials it might be reasonable to ask your mother’s oncologist about off-label dasatinib given the positive preliminary data out of MGH regarding it’s use in IDH-1 mutations. It is an oral medication with minimal side effects. Keytruda generally has less efficacy in patient’s without mismatch mutations, so it might be reasonable to ask about dasatinib first. Since the MGH dasatinib trial may already be closed it seems reasonable to at least ask about using it off-label.

Regarding an update on own mother, she has only been on AG-120 for about one week but surprisingly her LFTs have come down considerably, with her alk phos decreasing from ~600 to ~350, normalization of her bilirubin and transaminases (AST/ALT), and otherwise normal labs.

Hard to say what the lab results mean over such a short time, but it is nice to see the labs finally have some improvement. I’ll be sure to provide more updates as we go along.

Thank you for looking into it. I will contact the NCI MATCH team about her case. I think it certainly seems like dasatinib should be the next option if AG-120 were to not work (I hope it does work though). I also shot an email to the PI of the dasatinib trial at MGH to see if he has any thoughts (I’m not sure if that’s who you already reached out to…sorry if I’m repeating your work).

I have to say, I never would have thought that a discussion board would be a source of information for me as a physician myself, but this community has been incredibly informative and helpful. Thank you again for all that you have done.

Hi all,

This is my first post here. Thank you for all the incredible efforts of everybody here to keep the community informed of developments in the treatment of CCA.

I am a physician in Boston myself, but generally there is not a ton of exposure to CCA, and particularly not to any of the cutting edge treatments that occur mostly in trials. I mostly see patients that have the complications of CCA, such as cholangitis, etc. This forum has been helpful in my research.

My mother was diagnosed with intra-hepatic CCA in 12/2016 and has since progressed steadily through gem/cis and now FOLFOX. She does not have any extra-hepatic mets, but feels very unwell from the increasing tumor burden in her liver.

We are going to be starting the AG-120 trial on Wednesday after she has the repeat liver biopsy (ugh, I can’t believe she has to have three biopsies for this). I hope that it works. The dose will be 500mg per day, which I think is what was determined to be the maximum tolerable dose.

Also, her genetic panel came back showing mutations in IDH-1 and also ABL-1. I know that dasatinib has been shown to work on some IDH-1 mutant CCAs, but it is interesting because dasatinib is also used primarily for CML when there is a mutation in BCR-ABL.

I have been unable to find anything about the utility of dasatinib in patients with IDH-1 and ABL-1, or if dasatinib has any value when an ABL-1 mutation is present in a solid tumor.

Has anybody come across a situation like this? We are certainly going to try the AG-120 trial, but it would be good to know if there is evidence to suggest we should actually be moving forward with dasatinib as our next choice.

Thank you in advance!

– bostonguy

As a follow-up to the above thread, Sloan Kettering has a spot for my mother on the AG-881 trial I previously mentioned, which is a trial similar to the prior trial she was on that had some decent results (the AG-120). AG-881 is purported to be a next generation version of the AG-120 drug that, in the lab has been found to be a more potent inhibitor of the IDH 1-2 pathway. It is in Phase I stage so it is surely purely investigational and working towards determining appropriate dosage levels. It is a rather intensive trial and if she qualifies will require many batteries of testing and monitoring including biopsies, so it is no cake walk and, as with all trials, uncertain in efficacy. One positive with the biopsies is that Dr. Harding said they could test the tumors again for any other genetic driver mutations that might help with future treatment.

The other options are more standard line chemo, pursue other trials that might include pembro/Keytruda, or pursue obtaining pembro/Keytruda off label.

We also just recieved a call from Rutgers Cancer Institute of New Jersey letting us know they now have a spot open for Mom on the this immunotherapy trial (https://clinicaltrials.gov/ct2/show/NCT02586987?term=SELUMETINIB&state1=NA%3AUS%3ANJ&rank=2).

We basically need to make a go, no-go choice by the end of the long weekend so I am scrambling to try to understand what offers the best hope. If anyone has any thoughts, recommendations or experience with any of these options, I would really appreciate any information you could share.

On Tuesday, she had about 2.3 liters of fluid drained from her abdomen, which has offered her some relief, but I know we are surely at a critical juncture.

Thanks so much.

-Steven

Steven….we did the repeat PET/CT and the results are not good. After 2 months of Ag-120 there is significant new growth, so I am off the trial.

I am now looking at Keytruda off label as a possible albeit costly alternative. This would be something of a crapshoot given that in my case the predictive tests are either negative or unavailable. I had hoped that the tumor biopsy might reveal some new genetic alterations that could help when looking at new approaches, yet when asking repeatedly about the results of my biopsy I have only received evasive answers.
.
Looking carefully at the trial consent I signed, I now came across the following statement that I had not seen before:

“YOU WILL NOT HAVE RIGHTS FOR INFORMATION OBTAINED FROM YOUR TISSUE OR BLOOD SAMPLES.”

Could somebody please explain to me why anybody would wish to withhold from a trial patient information that could potentially save his life?
Best regards,
Paul