No TDM1 trial for me - DQ'd for Metformin use

[jml]

As this week marks 8 years since my diagnosis, I find myself still fighting, riding this rollercoaster of treatment and searching for NED.
After 8 weeks on Ixempra+Herceptin and a mixed response, but with liver mets progressing, I traveled from Atlanta to Indianapolis to screen for a TDM1 trial + additional study drug @Simon Cancer Center. Because of the very strict enrollment criteria, I thought I would only be screened, then wait-listed indefinitely.
Low and behold, when I arrived and met the doc, I was told that it looked like I would qualify and the did have a spot for me.
I was ELATED.
I had to complete additional screening tests-CT, Brain MRI, Cardiac studies, labs.The study would have required weekly travel for the first 6-8 weeks, but then settle into once/3weeks for the TDM1 infusion. They said the combo is really well tolerated and their patients have a great quality of life. This was so encouraging, in spite of the travel, because Ixempra has been a real challenge.
Yesterday would have been Day 1 of the study and my 1st infusion of TDM1.
Unfortunately, last Thursday the Research Coordinator called to tell me that the Sponsor (Genentech) had determined that I would NOT be able to do the study because I have been using Metformin for the past 7 years. (I was originally dx'd with Insulin Resistance from prolonged steroid/chemo exposure, but more recently have stayed on the drug because of the positive benefits with MBC).
Ironically, when I was being examined by the study doc and we were talking about my Metformin, she said she was aware of the research & would not ask me to stop taking the drug. But even though the docs believe in the benefits of Metformin, the potential toxicity when combined with the study drug is too uncertain, and they disqualified me from the study.
I was in shock and heartbroken and (still)scared as my options are few.
Their recommendation was to dc the Metformin asap x 2mos, then return to them to re-screen and repeat all the tests.But even if I did re-qualify, they didn't know if they'd have a spot for me in 2mos. So it looks like that study is completely off the table now for me.
Another irony is the Research Coordinator mentioned that there are some studies coming down the pipeline investigating the use/benefits of Metformin and breast cancer.
Oh, and the Brain MRI shows a 4mm spot on the frontal lobe. That's just too much for me to deal with right now, so my doc's suggesting we repeat the MRI in 4-6 weeks.
I'm feeling very confused and pretty dejected by all of this. We've shifted gears again and am pursuing SIR Spheres (radioactive pellets) for the liver mets and resuming Ixempra. This is a really good option for me, but still have to consult with the Interventional Radiologist, have some preliminary studies done on my liver before they green light the procedure. I'm so afraid they're going to determine that I'm NOT a candidate. I'm trying not to think about that and will keep my head and heart focused on having the procedure done on May 25th.
It's been a tough 18 mos, with multiple combos not working for me and then Ixempra working beautifully in some areas, but not in my liver.
I just want to get going with a plan and for life to resume some sort of balance.
This is a very weird time for me, reflecting on the 8 years of this bumpy journey, and feeling very melancholy and probably pretty depressed too.

So there you have it. Wish I were feeling more positive and optmistic, but I'm just not right now.
Waiting for Hope to find me~

Jessica

[schoonder]

Couldn't you qualify for the recently opened "expanded" access to T-DM1 trial? Does it have less restrictive exclusion criteria?
http://www.clinicaltrials.gov/ct2/sh...xpanded&rank=1

[Rich66]

Must be the DM1 component in question since it doesn't seem like diabetics using metformin are prevented from using Herceptin.

[jml]

Schoonder -We're currently looking into how to apply for the compassionate use program. But since we're uncertain how long it will take to get that lined up, we're moving forward with the SIR-Spheres procedure. We do know that the SIR Spheres will not exclude me from the program, so that's good news.
Rich-it's actually the PI3Kinase (targeted drug to reduce herceptin resistance) that they're being cautious about combining with Metformin. apparently both are pretty tough on the liver and effect platelet counts. the combined effect is unknown so better safe than sorry. though I'm still sorry I don't get to do the study.

thanks for your feedback.

[Rich66]

You mean the DM1 part, right?
Do they figure the insulin resistance from the premeds is permanent? Was it the standard Decadron type?
For what it's worth, cancer benefits of metformin seem to be present in less than diabetic dose. So if liver enzymes become an issue, might be possible to try cutting back before discontinuing altogether.
Are you taking Herceptin now?

[jml]

Actually, the study that I screened for in Indiana is a TDM1 + PI3Kinase (targeted drug to reduce resistance to Herceptin)combo. The TDM1 is an infusion q3weeks & the PI3Kinase is a drug taken orally x 14days.
I believe it's the PI3Kinase that they are most concerned about with regard to the Metformin.
Oh and here's a little history on how I began using Metformin...
After my 1st 49weeks of treatment, and finally NED, I started gaining weight, was constantly tired & lethargic, had a lot of blood sugar swings, etc. I went to an endocrinologist to be evaluated, assumed I was hypothyroid, but instead, they did a glucose challenge and determined I was insulin resistant - not diabetic, not pre-diabetic, simply insulin resistant, likely due to prolonged steroid exposure in the chemo pre-meds.
He explained that now that we are seeing more long term survivors, with longer treatment regimens they're discovering a new crop of secondary side effects, like mine.
I've never been re-evaluated, and honestly don't think I'm insulin resistant anymore, but have continued on the Metformin because of the research that supports its use with MBC. And while all my docs support continuing on the Metformin, I was ironically dq'd from the trial for it.

Are there many other folks out there using Metformin off label?