TAK-788 Trial

Sigh…why can’t things be uncomplicated….

Trial has started today, all is good, and my wife has taken her first dose of the pills. All is good except…we got a report of the MRI and apparently there are three small suspicious spots on the brain. Since the spots are so small, and my wife is completely asymptomatic, she is still in the trial, and in the “non-CNS involvement” cohort. But, now we wait to see what the MRI looks like in 8 weeks. The good news is that some recent studies suggest TKIs do a fairly reasonable job of treating targeted brain metastases as well, so this drug may deal with those small metastases as well. But at this point we begin to worry what if the TAK 788 works on the lung and liver and not the brain – do we still get to stay in the study if we have to do some radiation on the side?

There is something about “brain” that just feels different – gives you a different kind of shock. But, in reality, it’s just one more bump on this ragged road we travel…..

My wife felt a bit better after talking to the trial PA. The PA said the amount of cancer in the brain is extremely low, the trial drug does cross the blood brain barrier, and the results of the drug so far have been extremely encouraging.

After talking to the PA we are staying on the trial. But I suspect I am going to be very nervous in 8 weeks when it comes time for the new CT and MRI.

Moments of joy indeed! The blueberry/berry cheesecake I made for our anniversary last weekend may not last for another 8 weeks, so I may have to make a couple more!

Well, we won’t know how the drug is doing for a while, but the side effects are certainly starting – all manageable so far, but certainly more than Gemzar and different than POSSIBLA.

So for anyone else considering/starting the trial – here is a side effect update for day 4 – more along the lines of the Carbo/Alimta (but without the general 2nd day ache/crash – so I assume it isn’t affecting blood cells so much). Off and on diarrhea (no constipation as with POSSIBLA), some lip/mouth sores, and some heartburn. But luckily, like all of the other chemos, my wife has had no nausea at all! And, if other TAK patients are any indication, my wife is likely to start seeing some of the Acne-rash in about a week. Definitely seems like the side-effects are indeed like what I have read for the other TKIs.

However, the previous chemos has prepared us with our arsenal – Imodium/Pepto for digestive issues, numbing cream for lip/mouth, and some TUMS and watching out for spicy foods for heartburn (alas no acid controllers for the trial, as they need to try and standardize uptake, and reduction of stomach acid can affect drug uptake).

One thing we forgot to ask the trial oncologist was why the dosage is set, and not based on body weight (as all the infusion medications were, and my wife is rather petite) and if the dosage can be reduced on a Phase 2 trial if the side effects seem to be limiting at some point. But we will be seeing the oncologist again within the next few weeks, and the PA each week, for those and more questions we may have.

My wife has also noticed that she has to be very careful to swallow the 8 capsules one at a time, each with a lot of water, as the capsule coatings apparently cause the capsules to stick to each other, and they can get caught in your throat if each one doesn’t make it all the way down.

But, it certainly reminds me every day how amazingly strong and courageous my wife is!

Thanks onthemark! I hadn’t seen that one yet!

I have been keeping my eye on T-DM1 ever since the European HER2 study review showed it to be much more effective than afatanib, with a response rate of about 50%. It basically works much like my wife’s first trial drug, although that one targeted PTK7 (an adenocarcinoma target) rather than HER2. The European HER2 study showed the regular EGFR TKIs really weren’t that effective against HER2, which is why we will be anxious to see if the trial TKI my wife is on, designed specifically for Exon20 mutations, is (we hope!) a lot better. Since the antibody of T-DM1 targets the normal portion of HER2, it is thought (but not really known) that it might work better against amplified HER2 cancers (where there are a very large number of HER2 receptors on the cancer cells).

I have also mentioned T-DM1 as a future possibility for a friend of ours who has persistent HER2 breast cancer – it a rare form that shows up as a rash rather than any tumors, so the only way to treat it is to remove the affected area of skin and then treat with Herceptin or other anti HER2 drugs, and then just wait until it shows up again. There is a trial using T-DM1 for just that type of cancer, but it is overseas.

Glad you like the cheesecake! My wife loves cheesecake, so I often make one for our anniversary. Here is a lemon one from a couple of years ago.

Thanks again! scohn

Janine, Jim, and onthemark.

Just another quick thank you for, well, just being there. It’s a frightening and draining experience dealing with these wretched diseases, and it is so helpful to have others around to listen and help. So, thank you. I’m sure I will be saying that a lot more times…..

And you have all been so nice, I’ll give you a nice batch of homemade truffles. Perhaps that’s what I’ll do when I retire – sell some “Confections for Cancer – Help take a bite out of the disease!”.

All the best,
Scohn

Dear tarjones.

Thanks so much for the info! It is nice to know that there others out there on this same trial! My wife says making sure to take the capsules slowly one at a time has helped a lot for her. I'll let her know about the gelatin (where did you hear about that?). Even better to know that it has kept your Mother-in-law's tumors stable! Hopefully it will work as well for the HER2.

By the way, what were her other 4 prior lines of treatment? Where is your trial location?

The diarrhea has been bad off and on, but the worst has been the mouth sores and swollen/sore lips. The doctor told her they are actually not mouth sores but something else, I think it's more of like mouth acne sores. They prescribed minocycline for her and said if the side effects aren't better next week then they will reduce the dosage. They also gave her a mouth rinse she can use 4 times a day, and said she can rinse with a saline as often as she needs to. My wife is rather petite, and the doctor said that the dosage is initially the same for everyone, so she has the same dose as a 220 pound man, and reducing the dosage isn't a problem, and they have found very good effectiveness even at lower dosages. Now we just have to see if it has any effect on the brain lesions as well.

It hasn't kept her from normal activities, and we are going on a short trip this weekend, and are planning a longer trip to perhaps Vancouver later in the fall/winter.

In fact, she had some metastasis to the hip just before she went on Gemzar, which went away right with the Gemzar. Her hip pain seemed to be flaring up a bit again about 3 weeks after being off Gemzar, but seems have gone again about 2 days after she started on TAK 788.

All the best to you and your mother-in-law for a strong and sustained response!

And I have come up with perfect name for TAK 788: Eicossa (from the Greek for 20) or Excossa (if you want to get the Exon bit in there).

Best regards, scohn

OK - one more time! My wife just started at the lower dosage (120 mg) yesterday, and now we see how it goes! A little diarrhea so far, but it started much longer after taking the pills. There's some heartburn too. So, on we go, and we'll see what's what!

<p>My wife had her weekly check up yesterday and got permission to take famotidine (as long as, like food, it is not taken within 2 hours of taking&nbsp;the drug). &nbsp;They all thought that the &quot;stuck in the throat&quot; effect was due to acid reflux. &nbsp;So, my wife took the famotidine 2 hours before taking the pills and she said it went so much better! &nbsp;Pills went down, no &quot;I feel like I can&#39;t eat anything&quot; feeling for most of the day, and just much better general feeling overall. &nbsp;And she said that the diarrhea now seems to be localized to once or twice a day, at the same time, so a little pre-emptive lomotil or imodium and that seems to be mostly in check as well so far. &nbsp;Mouth seems to have dryness but no sores, and regular rinsing with salt water seems to keep that in check as well. &nbsp;Next week is the one month all day check up again, so we will see, but at least for the moment, it looks like the 120mg dosage will be tolerable, at least in the near term. &nbsp;The next few days will tell!</p>

My wife just had her one month full day test (they draw blood almost every hour for 8 hours to measure drug uptake into the blood, and take several ECGs). Luckily that's the last full day. She has one more blood draw today, then, if all goes well, just a check up every month.

Side effects are still pretty rough (but much better than higher dosage) but my wife says they are tolerable, at least for a month until we see the next CT/MRI results. Some diarrhea still 2-3 times a day, even with Imodium and lomatil, and more if she isn't careful not to eat anything with a lot of roughage or overly spicy. But she can at least eat things now, supplements if needed with pedialyte, and isn't dehydrated at all. The mouth is dry, but no mouth sores/infections, but the infections have gone from upper to lower, and she now has some infections in the toes of her feet (which have a lot of cracking). So, lots of salt soaking and antibiotic and anti fungal ointments for the feet. Some small skin rashes, but at the moment those seem to come and go very quickly, although she says when they go they leave patches of very dry skin.

So, hopefully the toe infections can be kept under control, and the rest of the side effects also manageable. Hopefully it is as my daughter says "If it's doing all that to your normal cells, just think of what it's doing to the cancer cells!".

Well, as before, the CT results are mixed. Main lung tumor, adrenal glands, lymph nodes all stable, but liver metastases are enlarging. She had an MRI on Friday, and we will get the results of that tomorrow when we meet with the trial doctor. I suspect with the liver metastases increasing she will be kicked off of the trial.

So.... my wife was not technically thrown out of the trial, as by the trial standards the average tumor increase was only 17% (20% gets you kicked off of the trial), but that is because it averages in the main lung tumor (which didn't increase at all) and the liver tumor (the two measured on CT increased in volume somewhere between 50-100%). Brain lesions also completely stable (big relief there). So.... we have a treatment with pretty severe side effects in which some tumors seem stable and others completely unhindered. The trial doctor suggested that given the pretty severe side effects, and the only partial effectiveness, it would be best to go off the trial now (since at the same growth rate we would be kicked off at the next CT anyway) and try for something else.The doctor suggested that my wife go on a new trial, which is one of the ones that is tryinf nivolumab woith other "mabs" to try and enhance the immune system's recognition of the cancer.  The idea is that they take a new biobsy, do histochmeistry to see which target proteins are on the cancer, and then based on the biopsy treat in one of the seven test arms of the trial. Real semi-personalized medicine.  They would also do sequencing on the new biopsy to see what other mutations might have accumulated in the liver.But the downside- definitely more experiemental - they really don't know how well any of these combinations are working - and the treatment does not cross the blood/brain barrier - so would have no effect on the brain lesions.So we need to decide - a more clasical chemotherapy (like Gemzar which had been working, plus possible liver radiation) or the new trial.So (lots of so's today) a lot of checking up on the new trial protocol, but if anyone has insights or information on any of these nivolumab "plus" trials, we would appreciate it.Thanks! 

Also talked to the good folks at the Exon20 Group today, and the head of the group was really pushing for my wife going into a Poziotinib trial, but it is in Houston. They indicated that several people who progressed on TAK788 have entered the trial and really showing good responses. Sheesh! So much to think about.

Thanks Dr. West and Janine - I really appreciate it! We are still in the midst of deciding what to do, but basically have looked over the ADVISE trial, and based on everyone inputs it just reinforced our own sense that it is really a very exploratory trial, particular with driver mutations, so we have mostly ruled that out and want to try something a bit more focused in the meantime. My wife's hip has started to act up (within 3 days of going off of TAK788) so we are pretty sure the tumor there is acting up again. So, at the moment we are looking at a docetaxel/ramucirumab combination either right away or after hip radiation, probably going for the former. My wife really likes how she feels after getting off of the TAK788 and is not anxious to start that up again with the poziotinib. At the same time, poziotinib is looking very promising, so we are hoping that it will still be available if needed after the taxel. But we should know what we are doing by the end of the week. Thanks again everyone!

Thanks everyone for your help!! Well, the decision has been made now, and my wife is going to go for the docetaxel/ramucirumab treatment, probably starting the week after next. She is going to go in for initial blood work and talking to the oncologist on Friday, but I don't think the actual treatment will start until a week or so later. Hopefully the hip pain will respond to treatment as quickly as it did with the Gemzar and TAK788. And we were happy to see a number of studies that showed the anti-angiogenesis drugs work in the brain. My wife is feeling much better now that she is off TAK788, and felt this approach would be more likely to give a good response with less side effects in the short-term. Jim - thanks so much for the info! Unfortunately, I think most of the main poziotinib trials are under a protocol that excludes people who progress on TAK788. The one in Houston is being done by one of the developers of poziotinib I think, and in any case he is under a researcher-driven protocol that gives them much more flexibility and allows those who were progressing on TAK788. So, once more into the breech - treatment line #6....

<p>Thanks for the good wishes Jim!</p><p>So, after talking with her oncologist, my wife decided to go with the taxol/ramucirumab combination. The oncologist said he is going to try to get approval with Abraxane, which seems to have a much better toxicity profile than the docetaxel. It would probably start next week or early the following week. Oncologist suggested there are lots of potential side effects to the ramucirumab.</p><p>But, he suggested that he would like to have her on the double immunotherapy trial treatment at some point.</p>