Tuesday 6 March 2018

What a crusher. It’s been almost 2 years to the day since this journey started and today we were told that this beast has returned. Waiting until Thursday for the tumor board to meet and provide their take. Meanwhile our NO threw out all the options...so we’ve got some though decisions to make. I hate this rolling the dice crap - at least that’s what if feels like.

Noteworthy regarding my wife's tumor testing -- was Methylated, IDH1 negative, there's EGFR amplification, positive for EGFRvIII, P53 positive, ATRX positive, and some PTEN imbalance. She's had a great 18 months since the end of SOC treatment -- as a matter of fact she's at the gym right now -- we've been lucky. 

My questions to the group are:

- do you have a success story since having a 2nd resection?
- who's having success in a trial and what is that trial?
- what's hot in world of trials?

FYI - we're located in Boston. Thank you all!

16 comments:

  1. One interesting trial recruiting in Boston is this one, though it is only phase 1 and I haven't seen any preliminary results yet:
    https://clinicaltrials.gov/ct2/show/NCT03152318
    A Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2
    https://www.cancer.gov/publications/dictionaries/cancer-drug/def/oncolytic-hsv-1-rqnestin345v2



    Elsewhere in the country there is

    https://clinicaltrials.gov/ct2/show/NCT02986178
    PVSRIPO With/Without Lomustine

    https://clinicaltrials.gov/ct2/show/NCT02798406
    Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects (CAPTIVE)

    https://clinicaltrials.gov/show/NCT02208362
    Genetically Modified T-cells in Treating Patients With Recurrent or Refractory Malignant Glioma

    https://clinicaltrials.gov/ct2/show/NCT02858895
    Convection-Enhanced Delivery (CED) of MDNA55 in Adults With Recurrent or Progressive Glioblastoma

    https://clinicaltrials.gov/ct2/show/NCT02414165
    The Toca 5 Trial (but this has an arm randomized to standard treatments only)

    There are also a couple trials for EGFRvIII specific CAR-T cells, and a couple trials for EGFR specific antibody-drug conjugates.

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  2. Thank you Stephen! To put you on the spot ...what in your estimation are the top 2 or 3 that worth looking seriously at?

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    1. Out of those trials my picks would be PVSRIPO (poliovirus), DNX-2401 (adenovirus) + pembrolizumab, and MDNA55 (because of the high rates of complete response [5/25] reported by the company, although this has yet to be formally published). Toca5 would also be on my short list, except it's randomized and half the patients get standard treatment only.

      If I recall correctly none of those first 3 trials include a tumor resection. If going for a second resection, SVG's advice below to allow for vaccine creation (probably in Germany) would be ideal if possible.

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  3. I remembered this "positive story" after 2nd resection:
    https://virtualtrials.com/survivematt.cfm

    Keep strong, I wish you all the best!

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  4. https://virtualtrials.com/survivetoms.cfm - Tom had a recurrence.

    So did Greg (this is Tocagen which Stephen mentioned) - https://virtualtrials.com/surviveGreg2.cfm

    And Cheryl Clark who is on Facebook also had a recurrence.

    Of course, there’s Cheryl Broyle’s too and probably more that I’m not thinking of right now.

    Maria

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  5. I am very sorry to hear about your wife's re occurrence.
    My daughter had a re occurrence this past September after 12 months free.
    This time it has come back in both sides of the ventricles and is considered in operable. Since December we have followed the the stories and medication practices of the likes of Ben Williams and others from this web site.
    My daughter has now had monthly MRI's since the beginning of December and although the tumour is very much still there, they have all come back as stable with no further disease progression. Ben Williams, Stephen W and the others on this site that have dealt with or dealing with this dreaded situation are a wealth of knowledge and provide at least some hope that you will not receive from the general medical institution. Don't give up our prayers are with you both

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  6. There are several long-term surviving patients in spite of relapsed GBM reported in the literature by several groups who receive active specific immunotherapy consisting of dendritic cell vaccination. If the tumor is still to be resected, then I propose to keep as much as possible of the tissue STERILE / DRY / FROZEN AT -80°C. Then this tissue can be used in the vaccine preparation. Some groups are indeed now combining oncolytic virus therapy with immunotherapy. As only a few groups are able to produce clinical grade dendritic cells, most use only checkpoint blockers and call that immunotherapy (although checkpoint blockers will not work if there is no antitumoral immune response present in the body - which can be induced with dendritic cell vaccination).

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  7. Hello, Do not have a final answer yet but I have been on the DNX-2401 trial since Nov2017. The MRI's have stopped showing growth but no shrinkage yet.

    Marc

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    Replies
    1. I think immunotherapy sometimes takes some time to show shrinkage - if I'm not mistaken I read about this in Toca 511 trial

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  8. UPDATE -- so the tumor board stated that there is another small area possibly of concern in addition to the recurrence seen in her original location. Their top recommendation was no to surgery but instead do CCNU and TMZ. They want to treat is "systemically". To me that sounds like a lame option - but I really don't know. So we went across town to Dana Farber and were given these 3 trials to consider that fit the bill for rGBM and availability. Two of them involve surgery. They are:

    1. The one you mentioned Stephen -- the herpes virus Phase 1 for safety and dosage http://bit.ly/2FxaWyU
    2. A Phase 1 surgical trial for EGFR amplified rGMB with Lapatinib. 2 arms - one with the drug before resection and the 2nd will get the drug after surgery http://bit.ly/2FvydBd
    3. Is a immumontherapy Phase I Trial of Anti-LAG-3 or Anti-CD137 Alone and in Combination With Anti-PD-1 http://bit.ly/2Fr9vSj

    I'd appreciate it if anyone can provide info or first hand experience of any of these, and if so, hows it going with tolerance/success etc.

    I was a little disappointed when I mentioned the MDNA55 and the Dr. was unaware and also mentioned it would be a big hassle to go elsewhere in the country. He didn't really recommend any other trials that are beyond Boston.

    Also, I'm a bit concerned with the small 2nd area of interest. Anyone out there dealing with a multifocal recurrence?

    Thank you all for your input and help!

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    Replies
    1. Interesting, I've never seen TMZ + CCNU combination used for recurrent GBM, but it will probably be tried more frequently now following the results of the CeTeG trial for newly diagnosed. CCNU alone for first recurrent, MGMT methylated GBM produces mediocre results in the phase 3 EORTC26101 trial:
      http://www.nejm.org/doi/full/10.1056/NEJMoa1707358 (I'll add the full PDF to the Library if it isn't there already)

      I'm intrigued by the modified Herpes Simplex Virus + cyclophosphamide trial, though it is a gamble as this seems to be a first-in-human trial with not much data to go on.

      I have a personal distaste for single agent kinase inhibitor trials (lapatinib, etc, etc, etc). These sorts of trials have failed over and over, although this particular trial isn't really an efficacy trial, it's a pharmacodynamic/pharmacokinetic trial to see what concentration of the drug can be achieved in the tumor and the pharmcodynamic effect on EGFR in the tumor. I wouldn't argue that kinase inhibitors have a use in GBM therapy, I just feel the patient would be much better off if they were integrated into a combination therapy. Single agent kinase inhibitor trials may be good for science, but not great for patients.

      The third trial, the checkpoint inhibitor trial, is also a bit of gamble: two groups get one of two experimental immunological drugs, and two groups get either of these drugs combined with nivolumab. The trial would be more appealing if you would be guaranteed to be in one of the groups getting nivolumab, which at least has some clinical data of activity for GBM.

      Has there been any discussion of radiosurgery (Gamma knife) for the small area of concern? This is just a one-time procedure that takes about an hour or less, as an outpatient. There is no conflict in treating the tumor both locally as well as systemically.

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    2. I've uploaded the EORTC26101 trial publication to the Brain Tumor Library: folder 1. Therapies - human studies -> 1. Randomized clinical trials

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    3. Thanks again Stephen. We actually already have a meeting at a Gamma Knife location on Tuesday to get their take! What is considered to be the largest tumor size that GK works on? I was hoping we could do both and then maybe do some chemo or trial.

      I misspoke regarding the CCNU and TMZ -- it would be one or the other -- sorry!

      Also, is it true that being IDH1 negative that procarbazine , Iomustine and vincristine would be ineffective and off the table for rGBM? Have you hear that?

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    4. I think the general guideline is that Gamma knife is used for tumors under 4 centimeters in diameter.

      I don't see why PCV would be off the table for MGMT-methylated GBM.
      https://www.ncbi.nlm.nih.gov/pubmed/16505319

      Procarbazine is a methylating/alkylating agent not unlike TMZ, and of course lomustine is used frequently for recurrent GBM. There is still uncertainty as to whether vincristine adds anything value to this regimen or only makes it more toxic in terms of side-effects. Some retrospective studies have showed procarbazine + lomustine (without vincristine) as being comparable in efficacy to PCV.

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  9. ▶ I thought I'd let the group know that our NO has agreed to start a TMZ along with CCNU regime for my wife's 1st recurrence. We'll be meeting today or tomorrow to get the details and it will be interesting to see what dosages etc will be. What were dosages for the CeTeG trial for newly diagnosed, and what have your regimes been if you've been doing TMZ or CCNU for your recurrence. Thank you.

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    1. The dosing schedule and protocol for the CeTeG trial can be found on clinicaltrials.gov

      https://clinicaltrials.gov/ct2/show/NCT01149109

      Day 1: CCNU at 100 mg/m2
      Days 2-6: TMZ at 100 mg/m2

      Dose of TMZ can be increased stepwise up to 200 mg/m2 if well tolerated.

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