Advice for a 8 year-old boy with diffuse midline glioma, BRAFV600E and H3K27M mutation

Dear Stephen, dear all,

Anatole, my 8 year-old son has been diagnosed in May 2018 with a diffuse midline glioma on the right thalamus. We are French and based in Stockholm, Sweden. We followed the proposed protocol with the local medical team who works in partnership with Gustave Roussy institute in France but we want to go further now, and we need your advice. The local medical team is not very aware of alternative medication but is willing to help.

Molecular status of the tumour:

BRAFV600E and H3K27M mutation

NF1 and MLH1 mutation

We have little chance to find new targetable alterations by a deeper sequencing. It is possible now that the V600E BRAF mutation is lost in the resistant cells but anyway we do not think it is wise to treat with a V600E BRAF inhibitor which in our experience could speed up tumor growth.  

History:

18/05/09 Diagnosis: MRI tumour size 3.3x3.7x3.7cm, unusual calcification

18/05/16 Biopsy, leading to light hemiparesis

Proton-therapy 18/07/02-18/08/13, 1.8Gy x 30 = 54Gy. Almost fully recovered from hemiparesis

18/09/07 Headaches

18/09/07 MRI tumour size about 4cm

18/09/12 Ventriculostomy

18/09/19 Beginning og Dasatinib (100+70mg/day), after 18/11/06 alternating with Everolimus (5mg/day) every 2 weeks (Biomede protocol)

18/09/22 Beginning of hemiparesis

18/10/03 Wheelchair for walks more than 20m

18/10/12 MRI tumour size 5 to 6cm unsure if pseudoprogession

18/10/22 Beginning of Bevacizumab then once every 2 weeks

18/11/06 Beginning of Everolimus  

18/12/03 MRI tumour size 4 to 5cm unsure if pseudoprogession

18/12/17 Crook for walks less than 20m

19/01/14 MRI tumour size 5x6x5cm

19/01/22 Stop all current chemo (Dasatinib and Everolimus, last Bevacizumab 19/01/02)

24/01/24 PET scan (methyonine)

New plan established by Gustave Roussy Institute: Mebendazol, investigation for debulking of calcification before re-irradiation, eventually ONC201
Any comment on this plan?

Supplements:

Anatole is 30kg 132cm  

D3 vitamin since 18/12/24: escalading from 40µg/d to 100µg/d now

Fish oil since 18/12/24: 1g

Melatonin since 19/01/10: escalading from 2mg/d to 5mg/d now

Turkey tail since 19/01/25: 500mg/d

We plan to add soon:

Longvida Curcumin: 800mg/d

Milk thistle: which dose would you recommend? 

Green tea extract: which dose would you recommend? 

Broccoli sprouts: which dose would you recommend? 

Metformin: Is it worth considering for a child?

Anything else you would find suitable considering his condition (celebrex, chloroquine, clomipramine, berberine, selenium, probiotics, etc?

Diet:

We follow a light low carb diet now (no refined sugar or flour, very limited sugar, no processed food, only bio food). We are planning to begin a ketogenic diet soon, we are ready to change all our habits. We will contact a dietetician specialist in this diet. Anybody else with an experience of ketogenic diet with children?

Thanks to all of you for your precious help, any contribution could help.

Fabrice

ONC201 expanded access for H3 K27M mutant gliomas

This is rather big news for H3 K27M mutant gliomas (including a high percentage of DIPG).

Expanded Access Program for ONC201 to Treat Recurrent Histone H3 Mutant Glioma (click here)

In a phase two trial of ONC201 for recurrent GBM, a 22 year old female with secondary H3 K27M mutant GBM achieved a partial response to ONC201, which has been sustained for over 6 months. One of her two tumors regressed by 85% and the other tumor regressed by 75% after 8 and 11 months of therapy.

A phase 2 study of the first imipridone ONC201, a selective DRD2 antagonist for oncology, administered every three weeks in recurrent glioblastoma  (click here)

Note that the H3 K27M mutation (also known as H3F3A K27M) is most common in brainstem gliomas of young children and young adults, including diffuse intrinsic pontine glioma (DIPG).  This treatment could turn out to be a breakthrough, as there is currently no known effective treatment for this tumor type.

Considering treatment options for high grade diffuse midline glioma H3k27m for my 8 year old daughter

Hi all,

Thanks so much to Stephen for your in depth reply to my questions about my 8 year old daughter and invitation to this blog. We moved to Norway in July and my daughter was diagnosed in early September with high grade diffuse midline glioma with H3K27m mutation after an extended biopsy, where it was determined that the tumor was not resectable. She underwent 3 further operations to have a double valve shunt put in to relieve hydrocephalus symptoms. She finished 6 weeks of radiation and Temodal about 10 days ago. The doctors want to start her on Temodal/Lomostine 4 weeks after radiation finished. If we follow this path, we could also have a full molecular analysis done and, upon recurrence, may possibly be able to access a trial using afatinib for BI1200.120, if applicable, or another targeted agent. I would also push for using repurposed drugs in the cocktail approach if possible and our conservative doctors could be convinced. 

We are trying to explore other options, and thanks to Stephen, learned about a new phase I peptide vaccine trial opening for paediatric glioma patients with mutation H3.3K27m based in San Fransisco. It is for patients who have completed 6 weeks of radiation and have not yet started chemo again, which is exactly where we are now. https://clinicaltrials.gov/ct2/show/NCT02960230

I am finding it so difficult to determine what would be the most promising, preferably least toxic option for my daughter. Any input on how promising a peptide vaccine targeted to this kind of mutation could be? Compared with temodar/lomostine/cocktail approach?

Many thanks in advance for your input.

Jeni