TAK-788 Trial - 1295011

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

Today's update - we went on a nice weekend in Wisconsin, but my wife was not feeling great most of the time. But she did perk up enough Sat. afternoon that we went kayaking!

Friday aft and Sat morning she had a couple of bouts of feeling really dizzy and nauseous, which we realized was due to the Minocycline she was taking - happened both times soon after she took it (they had prescribed it for the mucositis in her mouth). So, she stopped taking the antibiotic and felt much better, but the diarrhea was still taking its toll, and they told her today that she should stop taking the trial drug for a couple days. She has her regular appt on Weds. and I suspect, based on what they said before, that they will be reducing her dosage.

I'll keep you all posted!

My wife just got back from meeting with the doctor. Her mouth sores are definitely getting better, her blood tests were fine, but had really low blood pressure due to dehydration from all the diarrhea (which is just now starting to get a little better). So, they would like her to take a couple more days off from the TAK until she is feeling better, and then resume the trial drug at a concentration of 120 mg (down from 160). She was also prescribed a heavier duty medicine for the diarrhea in case she needs it. Between the harsh side effects of the TAK and the bad reaction to the Minocyclin, this last week was really tough for her. So some deep breaths, some relaxation, and onward once more....

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!