TG6002 oncolytic and vectorized virus, clinical trial for recurrent GBM in France

This upcoming trial in France is comparable to the Toca511/TocaFC trials in the US, in that it uses a viral vector to transmit a "suicide gene" to tumor cells that cause them to convert 5-fluorocytosine into the chemotherapy drug 5-fluorouracil.  The virus used in this trial, TG6002, is also oncolytic, meaning that it can kill tumor cells, even without the suicide gene + prodrug component.

https://clinicaltrials.gov/ct2/show/NCT03294486

More information on the lab studies with this therapy can be found here.

CCNU+TMZ - impressive outcomes for MGMT-methylated GBM

A reader of this blog kindly directed my attention to this breaking news, the first results of the phase III NOA-9 trial in Germany testing the combination of TMZ with CCNU (lomustine) for newly diagnosed MGMT-methylated glioblastoma.

"The mean median survival time in patients receiving CCNU was 46.9 months compared to 30.4 months in the control group with monochemotherapy."

The "mean" in the Google translation of the German language news report actually refers to the median (mittlere), as confirmed at the SNO 2017 presentation.

Although this was small for a phase 3 trial (only ~140 patients), a gain in median survival of over 16 months is unprecendented.

This will undoubtedly become the new standard of care for MGMT-methylated GBM.

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

https://forum.hirntumorhilfe.de/neuroonkologie/breaking-news-fortschritte-in-der-glioblastombehandlung-12606.html   (news article in German)

Psilocybin and end of life care

I'm aware that (like cannabis) psilocybin is illegal in most countries.  Psilocybin being the active ingredient in hallucinogenic magic mushrooms.  However, I've just became aware of an increasing body of literature (this research has really exploded since 2016) on the investigation of psilocybin for depression and anxiety, including studies on its use in terminal cancer patients.

There seems to have been an entire issue of the Journal of  Psychopharmacology (December 2016) devoted to this with original research papers:

"Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial."

"Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial."

and commentaries:

"Psilocybin-assisted psychotherapy for dying cancer patients - aiding the final trip."

"The role of psychedelics in palliative care reconsidered: A case for psilocybin"

"Psilocybin for depression and anxiety associated with life-threatening illnesses."

"Psilocybin and palliative end-of-life care."

"Psilocybin in end of life care: Implications for further research."

"Psilocybin for anxiety and depression in cancer care? Lessons from the past and prospects for the future."

This should be of considerable interest to the cancer care-giving community.  I plan on thoroughly reviewing this literature and writing more about it in the future.

Update: methadone

Hi,
my dad has just had his fourth MRI since being on methadone and it was very positive again. This time the tumor is stable but as the three MRIs before this one showed shrinkage, his tumor is now smaller than it was in the beginning. The latest MRI also showed that the edeme is decreasing in size. So we're happy :)
My dad was diagnosed in December 2015 with an inoperable glioblastoma (corpus callosum) and all doctors (neurosurgeon, oncologist, GP) are very pleased with the results. He's not using methadone alone but we've notived an improvement since he started taking it. He also takes Temodar, some other supplements and uses Optune TTF. So it might be the combination that helps him. I'll keep you updated on our experiences with methadone!

Trivalent CAR T-cells

This study, called Trivalent CAR T-cells Overcome Interpatient Antigenic Variability in Glioblastoma, just appeared as an accepted manuscript in Neuro-Oncology.  See abstract here.

This was a preclinical study tested in mice, but is an exciting development, as this CAR T-cell cocktail approach is more likely to be effective than CAR T-cells targeted to a single antigen.

I'll upload the full study to the Library (Immunology and Immunotherapy folder, in a new CAR T-cell subfolder).

New study from the Costello lab (UCSF) on IDH1 mutant low grade glioma

The study is called Clonal expansion and epigenetic reprogramming following deletion or amplification of mutant IDH1.  View abstract here.  I've also uploaded this to the Brain Tumor Library, Pathology folder, IDH-mutant glioma subfolder.  This data was presented at the SNO conference in Phoenix last year.  I'll be following up with comments, and perhaps an Astrocytoma Options update on this.

Immunotheraphy combo

Do you have any experience or thoughts about this study?
http://www.practiceupdate.com/c/57122/67/12/?elsca1=emc_enews_weekinreview&elsca2=email&elsca3=practiceupdate_braincancer&elsca4=braincancer&elsca5=newsletter&rid=MjMxMDE2NzMzNjcyS0&lid=10332481

Has anyone tried this combo?
Best wishes to all
Brainbutton

FIG-ROS1 Chromosomal Fusion Significance? Actionable?

My husband's genetic testing came back with a .51 Tumor Mutational Burden. He has a 66.40% TP53 Allelic Fraction and 45.76% PTEN. His NO said these are common in many cancers and said neither are very actionable.

He was intrigued by the FIG-ROS1 as it usually shows up in small cell lung cancer and with recurrence might be eligible for a bucket trial with entrectinib.

He also has CDKN2A and CDKN2B Copy Loss.

I am just starting to look into what all this means. I have not looked into clinical trials much but am pursuing possibly getting a PD1 Inhibitor although once again I am told he needs recurrence.

He is 7 months out, stopped adjuvant TMZ after 2 rounds, unmethylated, IDH Wildtype, doing Optune, supplements and cannabis oil and overall doing very very well. Thanks.

Suggestions for a Cocktail that does not include TMZ

Hello, my husband has stopped taking TMZ after 2 adjuvant rounds after having debilitating fatigue, dizziness and nausea. He is doing much much better. He is unmethylated and IDH Wildtype. When he was taking the TMZ he did take disulfiram and copper. He is also taking metformin and celecoxib. I know some of these drugs are meant to help the TMZ do what they are supposed to do. Does anyone have suggestions on what off-label drugs he should take if not taking TMZ?

He is taking the standard supplements as well as cannabis oil and wearing the Optune. Thanks.

Treatment Options for Glioblastoma and Other Gliomas - 2017 edition

This is the in-depth summary of treatment options that Ben Williams began years ago, and which I have taken over lately.  Download the 2017 update over at virtualtrials.com  , or click here for PDF download.   This can be discussed on Al Musella's BrainTumorTreatments yahoo group .  (Of course comments welcome here as well).

Partner due to have first vaccine as part of Duke Elevate trial on Wednesday.  He went through SOC and had 1st five day Temodar.  Duke said MRI two weeks after final radiation showed pseudo progression with swelling.  My question is does swelling eventually go down without steroids?  Symptoms have gotten worse in last week.  Concerned steroids might not fit with immunotherapy.  Haven't talked to doctor yet.

The Blood-brain barrier (BBB) and glioblastoma, a review

Another review appearing online as an accepted manuscript for Neuro-Oncology, on a tremendously important topic.  It's called "Is the blood-brain barrier really disrupted in all glioblastomas? – A critical assessment of existing clinical data" and shares my view:

"This review provides an overview of the clinical literature to support a central hypothesis: that all GBM patients have tumor regions with an intact BBB, and cure for GBM will only be possible if these regions of tumor are adequately treated"

Abstract here, and again I can email the full study if anyone would like a copy.

Key quotes below:

Combined with the surgical experience, these data support our central contention that all GBM have a clinically significant tumor burden ‘protected’ by an intact BBB.

Accepting the importance of drug distribution across an intact BBB into brain is a critical first step in developing effective therapies for GBM and must be a key consideration in any clinical trial design for newly diagnosed or recurrent GBM.

The impact of complete resection most important for IDH-mut astrocytoma

There is an important new study, just published as an early preliminary manuscript online in Neuro-Oncology, called "The impact of surgery in molecularly defined low-grade glioma: an
integrated clinical, radiological and molecular analysis".  This was a large retrospective study including 228 adult low-grade glioma patients undergoing resection since 2003.  The tumors were classed as A) IDH-mutant oligodendroglioma (with complete 1p/19q codeletion),  B) IDH-mutant astrocytoma (no 1p/19q codeletion) and C) IDH wild-type (GBM-like).

The most important finding of this study was that complete resection (0 residual tumor), was most critical in the IDH-mutant astrocytoma group, as seen in the following figures.  In the first figure shown below, even a small amount of residual tumor post-resection negatively affected survival for IDH-mutant low grade astrocytoma.

The next figure also shows outcomes for IDH-mutant low grade astrocytoma, by various amounts of residual tumor post-resection.  (My snip only shows the first 3 images in the series). 

The next figure shows that complete resection also improves survival in low grade IDH-mutant oligodendroglioma, but the difference in survival between 0 residual tumor and small amounts of residual tumor is not a large as for the astrocytoma group as we saw in the first figure.

The abstract is available here.  I can email the full study if anyone wants it.

GBM possible recurrence help

Hi all, my brother diagnosed with gbm last year april 2016 and got his surgery, radiation and temodal immediately after that. This year around feb 2017 during his 3months mri checkup the doctor noted a 0.75cm mass suspected as gbm. Bc its too small the doctor decided to wait for next mri to see how it goes. At may 2017 my bro undergo another mri and found out it was clear! But at next mri aug 2017 they found the 'dissapeared' mass to have grown to 1.4cm. The doctor have decided that it must be gbm recurrence, and he said that the missing mass in between these mri must be the gbm 'hiding'. Is it really possible gbm to be 'missed' during mri?

And we also really confused to the best solution in handling this 'possible gbm recurrence'. We have asked diff doctors including neurosurgeons and oncologists. Doctor A said we should go with gamma knife, Doctor B said we should go with Surgery instead cause Gamma knife wont guaranteed as clear as Surgery. Doctor C said Surgery is dangerous cause the mass is in a critical location that can 'paralyzed', and Gamma knife not effective so we should go with Cyberknife instead. Anyone who have experienced gamma or cyber which one is actually more effective for gbm? And for gamma knife do the patient need to undergo chemotherapy after the gamma knife operation like using Avastin? Or they can only wait for the gamma to works? We really appreacite any recommendations or sharing of experience. Thank you!

Regards,
Milee

ONC 201 plus ?

Dear all,
My son is currently on ONC 201 compassionate use trial (H3 K27 tumor recurrence). While our NO will most likely insist on just doing one-agent trial, I feel we should push for at least a consideration of adding another chemo to it. I think a combo of Avastin and Irotican could be reasonable - I read
that in mice, Avastin added to ONC 201 showed trifold efficacy. On the other hand , I am concerned about the long-term effect of Avastin. Any other ideas? I am just afraid to only stick with one gent. We can certainly just try to continue with CUSP 9 or medendazol.  Thanks!

Results of the "failed" rindopepimut ACTIV trial published

Rindopepimut with temozolomide for patients with newlydiagnosed, EGFRvIII-expressing glioblastoma (ACT IV):a randomised, double-blind, international phase 3 trial

Preparing for surgery - tumor analysis & storing

Hello all,

My sister's tumor (AA3) has progressed and a surgery is scheduled.
Would you do tumor analysis and if so, which one:
-Caris Molecular Intelligence
-Foundation One
-OncoDna?

We already know her tumor is IDH1 and TP53 mutated and MGMT methylated. No other mutations we're found last time. Also CD8+, PD1 and PD-L1 were negative. I don't know if there's much to gain this time, because it seems that the number of suitable chemos is anyway quite limited and PD1-inhibitors have shown low efficacy on IDH1mutated tumors?

And do you see benefit to store tumor sample for later use (e.g. Vaccine)?

Br,
Juha

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

Information on DCA and methadone

Hello all,
I'm looking for information on DCA. My dad was diagnosed with an inoperable glioblastoma in December 2015. He's doing pretty well at the moment and we're happy with his treatment. But we want to be prepared for the worst case and that's why I'm interested in DCA.
We live in Germany and as many other cancer patients my dad is taking methadone as part of his cocktail. That's also my main concern because I couldn't find any information on whether methadone and DCA can be combined (I read that you need to be careful with cannabinoids which could be problematic as methadone uses the same receptors). My dad's tumor was stable for a year and then started shrinking in December 2016. As you can imagine we're extremely happy and don't want to omit any of the drugs he's taking at the moment:
- Temodar (still on 5/23)
- methadone
- Optune TTF
- dexamethasone  (tapering 0,5 mg)
- Omega 3
- Vitamin D
- Levetiracetam
- Coriolus versicolor (PSK)
- broccoli sprouts
- Eliqius (blood-thinner)
If you have any information on the combination of DCA with our cocktail, please let me know. I'd also like to know whether you really have to be careful with the dosage in brain tumor patients. I read some really scary stories online, they said that the combination of DCA and caffeine was dangerous.
Thanks a lot!!

Boron-Neuron Capture Therapy (BNCT) to start in 2018

BNCT will be launched next year in Finland. They will start with head and neck cancers and include brain cancers in future.

http://www.neutrontherapeutics.com/news/pr_091516/