Thursday 22 November 2018

Hello Stephen, and all

My aunt's tumour was discovered about a week ago, and she underwent surgery shortly after. The doctor said he was able to remove about 60% of the tumour, which is in her right frontal lobe. She is 65 yrs of age.

Pathology Report:


·         Grade IV Glioblastoma
  • Tumour shows marked cellular pleomorphism, scattered mitosis, and microvascular proliferation.
  • There is no definite tumour necrosis
  • idh(-) wildtype, ATRX(+), GFAP(+), p53(+)
  • The ki67 proliferation status is estimated at 10%
  • Result of MGMT Gene methylation status to follow as an addendum….. still do not have it, but hoping to get this information at the first appt with the oncologist tomorrow morning*
I am trying to get as familiar as I can with GBM and I am doing some research on currently recruiting clinical trials so I can bring them along to the appt with her oncologist tomorrow.

I have discovered 2 trials that she seems to be eligible for (I hope), but I would like to make sure we are strategic in which we decide to choose (does trial phase matter?). I am very new to this topic and was hoping to get some of your thoughts on which might be more beneficial for my aunt based on previous studies etc. I did not see any info in the library about Avelumab (I think it is an immune checkpoint inhibitor) or Marizomib.
Also, in some trials there is the risk of being put in a control group, while it seems in the first trial below, all participants receive the new drug.

1. Avelumab in Patients With Newly Diagnosed Glioblastoma Multiforme (SEJ)
http://www.neuro-outaouais.com/glioblastoma-multiforme-clinical-trial/
https://clinicaltrials.gov/ct2/show/study/NCT03047473?show_desc=Y

2. A Phase III Trial of With Marizomib in Patients With Newly Diagnosed Glioblastoma
https://www.uhn.ca/PrincessMargaret/Research/cancer_clinical_research/Pages/clinical_trial.aspx?clinicalTrialID=8447#tab1

Any other trials or treatment options in Canada that may be worth looking at?

Any input is greatly appreciated,
Thank you,
Palma

3 comments:

  1. Checkpoint inhibitors (pembrolizumab, nivolumab, avelumab etc.) as a single agent are probably only effective in a minority of GBM cases. They can only work in cases where there are already T-cells infiltrating the tumor which are being suppressed by tumor-induced immune checkpoint mechanisms. In cases where there's not already a baseline immune response, checkpoint inhibitors won't do very much. This is why they work well in more immunogenic tumors such as melanoma. In GBM they will probably be much more effective in combination with vaccines that can induce an immune response where one doesn't already exist.

    If you are in the Toronto area, you might want to save the checkpoint inhibitor option for later, where you could get an oncolytic adenvirus (DNX-2401) in combination with pembrolizumab. If she does avelumab now she would be excluded from the DNX-2401 + pembrolizumab trial.
    https://clinicaltrials.gov/ct2/show/NCT02798406

    Some people following the blog have been participating in this trial.

    I'm not entirely sold on marizomib. Response rates have been good when combined with bevacizumab (Avastin), but not necessarily more than you would expect with Avastin alone. The marizomib trial is also randomized, so only 50-50 chance she would get it. I would still consider this trial though, because there are very few clinical trial options in Canada, and there's a chance it could work.

    I would normally say the same for avelumab as well (might as well try, there's a chance it could work), but I would hesitate as joining that trial would exclude her from DNX-2401 + pembro trial at recurrence and I feel there is more of a chance for checkpoint inhibitors to work in combination immunotherapy, rather than single agent immunotherapy. There were a few exceptional and long lasting reponses in the phase 1 trial of DNX-2401 by itself.

    See the Brain Tumor Library, folder 1, DNX-2401 subfolder for a copy of the study published this year.

    Let us know when she gets MGMT results back, and also I would ask about testing for EGFR amplification. She may be able to access ABT-414 if positive for EGFR amplification.

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  2. Thank you Stephen. This is very helpful. Sure, and I will ask about EGFR.
    So if she were to participate in the Marizomib trial, would she still be eligible for the DNX-2401 at recurrence? I think I am leaning towards that one at the moment.

    Also, in terms of the "drug/supplement cocktails" would being on one of these affect your eligibility for clinical trials? I do have a cocktail that I plan to show to the doctor. I know there is a very small chance she would be on board with it anyways, but I need to try.

    I just want to say that this past week has been a living nightmare for my family and I, and this resource provides a little bit of light in all the darkness. So thank you.
    Palma

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    Replies
    1. Prior treatment with marizomib should not exclude her from DNX-2401 trial. Avelumab would exclude her because it's in the same class of drug as pembrolizumab (anti PD-1/PD-L1).

      Off-label repurposed drugs and supplements are kind of in a no-mans land. They aren't usually specifically mentioned in trial protocols. If they aren't officially cancer drugs they wouldn't necessarily be part of the formal exclusion criteria of a clinical trial, as they are thought not to be effective against cancer (at least in popular opinion of oncologists).

      Keep us posted on any news or additional info.

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