Sunday 27 August 2017

First recurrence final decisions - KPS score improvement and DCVax trial?

Hi all,

My Dad completed his 6th round of TMZ (after completing the standard chemo-radiation) and unfortunately his most recent MRI (8/10/17) showed the first sign of recurrence. Substantial tumor growth for it only being two months from his last image. He is MGMT methylated but TMZ seems to no longer be effective.

We were not surprised to see tumor growth on his recent scan, as his condition had declined. This was in part due to us weaning off decadron. We got down to 2mg/day from 4mg/day.

At this point he is very weak, back to 6-8mg/day decadron and has a KPS score of 50 (due to the daily care necessary).

Our NO at UCSF, who we do trust, feels it is time to bump the decadron up and live out life with quality. He feels trying other chemos could be too toxic for his current condition and he wouldn't have a chance at getting into various clinical trials due to his decadron usage and KPS score. I understand this point of view.

One thought that our family is discussing is getting another Avastin Infusion. This would be his 3rd infusion, last one being in April. We know this is not a cure, but we think it may be able to lower his decadron use (to the <2mg/day as required by trials) and hopefully bump his KPS score back up to 70 (for trial entry). We had good results with his first two infusions.

Our NO understands this plan, but has stated that an Avastin infusion near the end of life may extend life a few weeks to months, but often times a very poor quality for the patient.

This is obviously a tough decision as we would only use the Avastin if we thought it could give us a chance to get into a worthy clinical trial. The DCVax trial at UCLA is our top pick currently. I meet with Dr. Timothy Cloughesy (UCLA NO director) tomorrow and will ask his opinion. We have also heard rumors that some trials will not allow you to take Avastin infusions right before treatments that involve resections, such as this one.

I know it's not an easy post to respond too. Any advice would be appreciated. I will update after my meeting with Dr. Cloughesy.

-Ari


UCLA - https://clinicaltrials.gov/ct2/show/NCT03014804?term=NCT03014804&rank=1

Duke trial below was our second favorite trial, but we would not be able to get my Dad to the East Coast - https://clinicaltrials.gov/show/NCT02986178




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7 comments:

  1. David27 August 2017 at 15:23

    Those are two of the best clinical trials available.

    One problem is that the DCVax trial requires surgically accessible disease to help produce they vaccine. They need fresh tissue.

    The viral therapies also require access. A company called ZIOPHARMA has a viral therapy study at Cedars, it might be at UCSF soon, the virus is called - Ad-RTS-IL-12. Nancy Ann Oberheim Bush MD, PhD at UCSF might be a good contact.
    https://clinicaltrials.gov/ct2/show/NCT02026271

    Also there is a good T-cell trial at City of Hope.
    https://clinicaltrials.gov/ct2/show/NCT02208362

    The Avastin could might be needed to get him well enough for a trial. The functional status may be a problem. Dr. Cloughesy is one of, if not the best in the world to consult on this.

    There is also a Dr. Kesari in Santa Monica, he might be worth consulting.

    Another thing is, has the tumor been evaluated through molecular profiling?
    Has EGFR been interogated as a possible target? ABT-414 etc.,

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  2. Sheena27 August 2017 at 15:54

    I am just echoing what David said. Try to contact T Cell trial asap. Getting to start the trial takes months, so they allow you to do other treatments in the mean time. In this case, Avastin would work. Paige is the one to contact there (phone number on clinical trials webpage). We just got back from seeing all the brain tumor centers in LA ourselves. UCLA tries their best to help. There is a trial at UC Irvine which their doctor, Dr. Bota, says is good (https://clinicaltrials.gov/ct2/show/NCT01903330), but would require probably moving there. Also it is randomized and double blinded. However, if you do not get treatment, and progress, then they switch you to treatment arm. Non-treatment arm is Avastin only. Dr. Kesari is excellent! If you are in the area, it would be good to consult with him. He is innovative and fights for his patients. Let me know if you need contact info for any of these. We also went to Cedar Sanai but they don't have too many trials at the moment, and the one they do have, requires surgery.

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  3. Anne Marie28 August 2017 at 08:32

    Ari
    I'm sorry you are going through this, it's horrible trying to decide what to do for the best. My husband had a second recurrence in May, substantial growth in just one month. He managed one round of PCV but was too unwell to take more - it seemed to affect him much more than TMZ which he tolerated well first and second time around. I can't advise you on trials but wanted to say don't give up hope, even if you can't get on a trial. Medics had started the conversation with us about end of life wishes etc. Then latest scan done last week showed a slight reduction in the tumour, which was clearly a surprise to everyone. The only medication/supplements he has had in the last 3 months are Keppra, Dex, Curcumin, Vit D3 and Sativex. The latter just introduced in May. I have no relevant qualifications but I don't believe this to be a coincidence.
    best of luck

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  4. Unknown28 August 2017 at 11:03

    David, Sheena, Anne this all helps. thank you for your advice.

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  5. Stephen W29 August 2017 at 03:22

    Have you consdered the DNX-2401 trail, also recruiting at UCLA (PI Tim Cloughesy)? You would still have to get steroids down, but this trial is for tumors where no surgery is planned and doesn't seem to exclude prior Avastin use.
    https://clinicaltrials.gov/ct2/show/NCT02798406

    Given the MGMT methylated status, this increases the risk of hypermutated recurrence (in which case anti PD-1/PD-L1 therapy could be more effective).

    Would insurance cover a second Foundation analysis? Also, were there any other alterations detected on the first Foundation report, besides CDKN2A/B deletion. MDM2 amplification is sometimes seen in GBM and is a risk factor for hyperprogression following anti PD-1 therapy.

    Given the good results you've had with Avastin in the past, another round seems reasonable to me, and could help reduce the steroid dose, and who knows, might even improve his KPS.

    What was Dr. Cloughesy's opinion?

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  6. Unknown29 August 2017 at 22:35

    Hi Stephen, Thank you for the response. It means a lot to me that you remembered my Dads foundation one report and previous post. I don't know that we have looked into the DNX-2401 trial although I'm consulting with a close friend who may have.

    Unfortunately I worry my dad would be excluded due to the fact that his recurrence is now showing on both sides of the brain. Originally left frontal lobe and moved towards right frontal. This is actually what Dr. Cloughesy mentioned about the other trials we were interested in as a major exclusion factor. Was difficult to hear this.

    Another reason for not being allowed into the DCVax was that they look for people who can have ~80% of their recurrent tumor resected during surgery. In our case the tumor was "large enough" for the various trials involving resections but Dr. Cloughesy did not think it would be safe to remove as much as 80% in this case.

    The only items Identified on the original Foundation One report were:
    PIK3CA C901F
    CDKN2A/B loss
    TERT promoter -146C>T

    The CDKN2A/B loss - seems to be the only interesting item to both Dr. Butowski and Dr. Cloughesy. They've mentioned the parp inhibitors (Abemiciclib) but neither has had great results with this.

    I'm assuming there is no way we could get his recurrent tumor tested without going in for another surgery? The discussion of getting his recurrent tumor tested to see whether it would have different genomic alterations never came up.

    With the potential of no trials in reach our next decision is whether to go with another avastin infusion or not. Dr. Butowski recommended against it saying it can extend life minimally but does not help with quality and sometimes does the opposite. Dr. Cloughesy said we should do it, as anything to lower decadron is good even in the end. Both had slightly different opinions here. I am leaning towards it if his health permits.

    We will keep up with the CBD oil and various supplements we find value in and keep looking for the next best option.

    Thank you again for all you do

    Ari

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    Replies
    1. jenna7 July 2018 at 05:12

      Hi Ari,

      I'm new to the community (my 34yo brother has stage 4 GBM) and was searching the forum for DCVax conversation.

      I called UCLA yesterday to get an update on the trial. The woman I spoke with seemed like she'd been entertaining lots of patient requests and was firm with me that she could not give me any information. She also mentioned she was sure they wouldn't get the trial approved this year.

      I was just curious if you received any other information from Dr. Cloughesy.

      Also, how is your dad doing?

      Have you guys considered looking into GcMAF? I also searched here for this and there seems to be a little info, but opinion on it seems to be iffy.

      Thank you for your time.

      Delete

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