Has anybody else had the experience of travelling to the US to access clinical trials? I understand that it will be extremely expensive, and a logistical challenge to organise. We are willing to take on the expense if it is a trial that is worth it. Really wanted to hear from anybody else who have gone down this path.
We are also only starting to look through trial options, primarily in the US. If anybody has any recommendation as to the most promising trials that are happening at this point, we would really appreciate any guidance and advice.
As we touched on by email, I think first you should find out if her Australian medical coverage would apply to surgery outside Australia, if it was in order to join a clinical trial not available in Australia.
ReplyDeleteBrain surgery is incredibly expensive as an out-of-pocket expense. For IDH1-mutant tumors there is very good (albeit preliminary) data for Toca511/TocaFC.
http://meetinglibrary.asco.org/record/152108/abstract
So first question for this or any other surgery based trial: would the Australian medical coverage cover the cost of surgery within a US clinical trial?
Keep in mind the case of Ben Williams - who also had an IDH1 mutant grade 4 astrocytoma (still officially termed a glioblastoma, but the terminology is likely to change over the next few years, with IDH1 mutant grade IV astrocytomas coming to be called "grade IV astrocytoma", rather than "secondary glioblastoma"). While his cocktail was initiated during the radiation phase of treatment (unlike your case where radiation and some cycles of TMZ are already completed), it's still worthwhile to review what he did. CCNU + verapamil could be a start. I would also consider PARP inhibitor (olaparib) based on more current data.
This is not to discourage you from clinical trials, just a reminder that there are options beyond clinical trials if that doesn't work out.
Hi Stephen,
ReplyDeleteThanks for following up here as well. Really appreciate it.
What is the significance of the difference between the classification of the progression as Grade IV astrocytoma, rather than secondary GBM? Does the difference make a practical implication to the treatment method and options available?
Our NO is on the path of recommending Avastin to us, and hasn't mentioned verapamil or olaparib to us as options. It might take quite a bit of convincing to be able to get support to try anything outside of Avastin at this stage.
The distinction between a grade IV astrocytoma (IDH1 mutant) and glioblastoma (IDH1 wild type), would not have a practical implication under current conventional oncology practice, as treatment is currently no different for these two types of tumors. However it's important to recognize the biological differences between these two types of tumors, which is now reflected in the official classification of central nervous system tumors as of 2016. Because of this, clinical trials are now paying attention to the IDH status of grade 4 gliomas, and will probably start providing separate outcome analysis. I would hope that in the future this would lead to different standards of care for these different types, as treatments are identified which are more/less effective for these types dependent on IDH status. We are not there yet, and currently there is no difference in treatment as far as the "standard of care".
DeleteVerapamil is not a cancer drug, and there is no oncologist I'm aware of who would recommend it. The only reason I mentioned it is because it was part of Ben Williams cocktail back in 1995, when he used it on the days surrounding his use of CCNU during his PCV regimen. We don't know that adding it to chemotherapy made any difference, but we do know that *something* worked for him.
Olaparib is in clinical trials for glioma, but almost no oncologist would mention it to a glioma patient outside the context of clinical trials. It is an ovarian cancer drug and its use for glioma would be very much off-label. This drug would be tricky to add to a glioma cocktail, first in terms of getting a prescription, and then in terms of the expense (insurance not likely to pay, because it is non-standard for glioma).
From what I've observed, it's usually easier to get prescriptions for non-cancer drugs from a primary care provider/family doctor/GP than from the oncologist.
What is this oncologists opinion on the use of CCNU for your wife? Is he discouraging it? What are his/her reasons? This is an example of where I think it could be important to treat IDH1 mutant versus non-mutant GBM differently, because VEGF-A (the target of Avastin) may be more involved in the pathology of IDH non-mutant GBM versus IDH-mutant GBM. This appears to be true on the mRNA level, but I can't say it is necessarily true on a protein level, and someone really should study this. We already know from the TAVAREC trial (for grade 2 and 3 glioma, 1p/19q intact) that first-line Avastin gave no benefit in terms of either progression-free survival or overall survival, unlike in GBM where we usually see an improvement at least in progression-free survival. Whether or not this is also true of grade IV IDH-mutant gliomas remains to be seen. Another thing to consider is that in the BELOB trial (randomized phase 2), combining CCNU + Avastin led to better outcomes than either drug alone, for recurrent GBM.
Hi Raymond, have you looked at the MoSt trial at The Garvan Institute in Sydney?
ReplyDeleteHi can you tell me the Bem cocktail my wife has a grade iii astrocytoma stephen please i saw many diferents and it has no clear time to take that.
ReplyDeleteMy best guess is that you're asking about Ben Williams' cocktail. There's a timeline and summary of what Ben did back in 1995 here, with details mostly compiled from his book. (two-thirds of the way down this page ->)
Deletehttp://astrocytomaoptions.com/exploring-strategies-for-idh1-mutated-gliomas/
Was your wife's tumor tested for the IDH1 mutation?
Is your wife newly diagnosed? Post surgery? With recurrent tumor? Also which country are you in?
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