LDK378

Yesterday I met with a doctor at Fox Chase Cancer Center to learn about the clinical trial for LDK378, a second-generation ALK inhibitor developed by Novartis.

The trial is currently in the second part of phase 1.  At this point, any newly enrolled participants will take 750mg of the drug once daily in pill format.  This was deemed to be the highest safe dose as found in the first part of phase 1.

There are currently 90 or so people taking LDK378 worldwide.  To date approximately 80% of those patients have responded to the drug (tumor shrinkage or stability).  That’s a great success rate.  When I asked the doctor about duration – how long the response lasts – she said it was too early to determine.  (When I was on Xalkori, I had a positive response but only for a short period of time.)

SIDE EFFECTS
The most common side effects have been nausea, vomiting, and diarrhea. There are others too, such as elevated liver enzymes, that occur less frequently.

My concern, of course, is that I will have nasty side effects like I did with Xalkori.  Part of my frustration was because what I experienced was extremely rare.  It sucks when you have something going on in your body, you tell the doctor, and they can’t say, “yes, that is attributable to the drug.”   Instead you feel like maybe you’re losing your mind and becoming a hypochondriac.  You wonder if that’s what the doctor thinks too.  Now you don’t feel good, AND you’re worried that people think you’re some kind of drama queen.  I had crippling back pain and treatment-ending abdominal issues with Xalkori; many people have very mild or no side effects.  With Gemzar – a drug that has a reputation for being very gentle – I had hair loss, fevers, aches, chills, and sweats.  If there is a freak side effect, I will find it!

There is protocol built into the trial to allow for very specific dose reductions if necessary.  Although it didn’t help when I tried it with Xalkori, it’s good to know that the doctor has that option should a serious side effect develop.

ELIGIBILITY
There is a screening process where data is collected and sent to Novartis to determine participant eligibility.  The screening consists of a CT scan of the chest, an MRI of the brain, various bloodwork, a complete review of medical history and specimens available, and more.

Although I’m not 100% sure I’m going to participate, I’m leaning that way and want to know if I’m eligible.  Therefore, I signed the consent forms today to move forward with the process.  I can say “stop” at any time.

Finally, I asked if Novartis was providing the drug in cases of ineligibility.  This is called “compassionate care,” and they are not doing so at this time.

TREATMENT CYCLE
Treatment runs in 21-day cycles.  Cycle 1 is the most intense with 5-6 visits during the 21 days.  The first day is a long one (10 hours) where they take blood as various intervals throughout the day.

Cycle 2 begins with another long day followed by a visit each week.  Cycle 3, 4, etc. require visits only on the first day of the cycle.  There may be weekly blood draws needed, but the doctor said they can write a script so i could have them done locally.

There is no end date to the trial.  If it’s working and there are no other extenuating issues, you can continue to take the drug.  As I mentioned before, a participant can withdraw from the trial at any time, for any reason.  Novartis and the doctor also have the right to end a patient’s participation based on certain criteria.

NEXT STEPS
I’m going to call my oncologist and discuss everything with him later today.  I expect to make my decision at that time.

My screening for the trial will probably take place the week of November 19.  If I’m accepted and decide to move forward, my first cycle would begin November 29.

I have a lot of mixed feelings right now.  About the trial, about the idea of losing my hair if I go through with another chemotherapy, about how much time I have left.  We (my doctor and the others I’ve consulted with) have always referred to a clinical trial as something you do when the commercially available treatments have failed.  And while I knew this day would come, I wasn’t expecting it so soon.

I think that’s what is bothering me most about doing a trial.  This might be the beginning of the end.  On the optimistic side, this drug could help me for a year before I develop a resistance.  At the other end of the spectrum, I could discover it is also toxic to me, which would suggest all ALK inhibitors may be.  Whenever it stops working (because eventually it will), I will look for another trial or return to chemotherapy and keep searching for one that might help.

I have a dozen other things swimming around in my head right now, but they aren’t yet fit to share.  I’ll let you know in the next few days what I’ve decided.  If you have any questions or think of something I should ask the trial doctor, please feel free to leave a comment.

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3 responses to “LDK378

  • Craig

    It sounds to me like all up-side and no down-side since you can always quit the trial and there’s the option of reducing the dose of this more-potent-than-Xalkori drug and still getting a benefit.

    Not all ALK drugs are exactly alike. Maybe the main side effects that people commonly get might be stronger since the selectivity of the drug lets them use a stronger dose and the potency is stronger, but other side effects might be milder because the collateral effects on different expressed genes can be different for different drugs. For example, besides ALK (and ROS1) Xalkori also inhibits cMET; AP26113 doesn’t also inhibit cMET but inhibits IGF-1R. (I don’t know about LDK378’s differences.)

    The big question seems to be whether you’ll be in that 80% that responds. Keep in mind that “response” usually means 30% or better shrinkage and with inhibitor drugs there’s usually even more patients who see mere stability, so the odds of benefit seem very high *if* your cancer is driven by a variant of ALK that the particular drug is potent against.

    So I’m going to be not just hopeful but optimistic for this helping you this time (assuming you can tolerate some level of it), but the only way to know will be to try it since it’ll depend what variant of ALK you’ve got and whether there’s any other driving mutation in there. Given your age means you probably haven’t had a lot of accumulated carcinogen exposures prior to your diagnosis and treatments, I’m hopeful for you and optimistic. (In my personal unprofessional opinion.)

    Best hopes,

    Craig

  • Monica

    Hi Jessica, I just found your blog the other day and it seems as though we have a lot in common, I am 35, also Stage IV NSCLC (dx Sept 2009) and am in the process of switching from Xalkori to LDK378. In fact, I just visited Fox Chase this week myself. If you are able to send me an e-mail (not sure if this blog allows you to see my contact info) I’d be happy to share my story.

    Monica

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