The Toca 5 randomized phase 3 trial has re-opened

The Toca 5 Trial: Toca 511 & Toca FC Versus Standard of Care in Patients With Recurrent High Grade Glioma (Toca5)

This trial is now open again, although only at 2 centers according to the clinicaltrials.gov listing (Edmonton Canada, and New Jersey).

NCT02414165

SNO 2017 Highlights: Intravenous administration of Toca 511

Intravenous delivery of Toca 511 in patients with high grade glioma results in quantifiable expression of cytosine deaminase in tumor tissue

Tobias Walbert of Henry Ford Hospital presented results of this phase 1 trial, which tested administration of the Toca 511 virus by intravenous injection.  Toca 511 is a retroviral replicating vector that transmits a gene to infected tumor cells.  This gene, cytosine deaminase (CD) causes the cell to convert orally administered Toca FC (an extended release version of 5-fluorocytosine) into the active chemotherapy agent 5-fluorouracil.  Following intravenous injection for 1, 3, or 5 days, tumors were resected and additional Toca 511 was injected into the tumor cavity walls.  This pre-resection intravenous administration allowed investigators to analyze tumor tissue for detection of cytosine deaminase (CD) within tumors.

17 patients were included in this trial.  14 of these patients (82%) had diagnoses of GBM and the remaining three had grade 3 gliomas.   47% were at first recurrence while 53% were at second or more recurrence.  

11 of 17 (65%) resected tumors were positive for cytosine deaminase, showing that intravenously administered Toca 511 successfully entered into tumors in the majority of cases. Analysis of resected tumor tissue following intravenous Toca 511 injection found that tumors with high T-cell infiltrate did not limit the ability of Toca 511 to enter tumor cells.  Conversely, the presence of immunosuppressive regulatory T-cells (Tregs) were also not required to allow entry of Toca 511 into tumor cells.  

The maximum tolerated dose of Toca 511 was not defined and grade 3 or higher adverse events were rare, occurring in only 3 patients (17.6%). 

Stable disease was achieved in 3 of 17 patients (17.6%) and late onset (>12 months after treatment) radiologic responses were seen in two of 17 patients (11.8%), consistent with an immunologic mechanism of action.  The responding patients were an IDH wild-type anaplastic astrocytoma patient at 3rd recurrence, whose response was noted on MRI 9 months after discontinuing Toca FC and was on no other anti-cancer therapy;  and an IDH1-mutant GBM patient at first recurrence who had onset of response 13 months after initiating Toca FC.  Complete response was eventually achieved in this patient, and response has lasted for 16 months and counting. This patient remains on Toca FC and no other anti-cancer therapy.  Median overall survival from trial entry for this group of 17 patients, 53% of whom were at second or more recurrence, is 13.6 months.

This trial is one of three phase 1 trials of Toca 511/ Toca FC for recurrent malignant glioma, which are all now closed to recruitment.  Currently recruiting patients is the Toca 6 trial for recurrent solid tumors, and the randomized phase 2/3 Toca 5 trial for recurrent malignant glioma, which has just reopened as of November 2017.  A phase 1 trial of Toca 511/ Toca FC for newly diagnosed malignant glioma (Toca 7) is scheduled to open in 2018.

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SNO 2017 Highlights, episode 3: Marizomib +/- bevacizumab for recurrent GBM

Full enrollment results from the phase 1/2, multicenter, open-label study of marizomib (MRZ) +/- bevacizumab (BEV) in recurrent WHO grade IV malignant glioma

Daniela Bota of UC Irvine presented these results.  The trial was divided into three parts: Part 1 was a dose escalation and dose expansion trial of the brain penetrant proteasome inhibitor marizomib added to bevacizumab and consisted of 36 patients.  Part 2 was a trial of single-agent marizomib consisting of 30 patients.  Part 3 was an intra-patient dose escalation of marizomib combined with bevacizumab consisting of 35 patients.

In Part 1, 27 out of 36 patients (75%) were treated with 0.8 mg/m2, while 9 patients (25%) were treated at lower doses in the dose escalation phase.  Patients in Part 1 also received standard dose bevacizumab.  The overall response rate for the 36 patients receiving marizomib and bevacizumab was 16/36 or 44.4%.  11/36 or 31% had stable disease.  Response plus stable disease rate is 27/36 or 75%.  Median progression-free survival was 3.9 months and median overall survival was 9.4 months.

In Part 2, 30 patients were treated with marizomib alone.  In this cohort there was only 1 partial response (1/30 or 3%) and 6 with stable disease (6/30 or 20%), for a response plus stable disease rate of 23%.

Patients in Part 1 experiencing central nervous system related adverse events (including ataxia, balance disorder, dizziness, fall, gait disturbance, hallucination) had increased PFS and OS compared to those who did not suffer from these side-effects, and this observation provided a justification for Part 3 of the study, an intra-patient dose escalation of marizomib combined with bevacizumab. In Part 3, 10 out of 35 patients were escalated to 1 mg/m2 of marizomib, but only 1 patient was able to tolerate this dose.  No patient reached 1.2 mg/m2.   The intra-patient dose escalation can therefore be said to have not succeeded, as the next higher dose of 1 mg/m2 was largely not tolerated.

It appears that single agent marizomib has some activity, but only for a minority of patients, while adding bevacizumab to marizomib leads to much higher response rates and increased survival at 12 months, but still leads to an average median overall survival statistic for recurrent glioblastoma.

SNO summary, episode 2: AG-120 phase 1 trial for IDH1-mutant glioma

AG-120, a first-in-class mutant IDH1 inhibitor in patients with recurrent or progressive IDH1 mutant glioma: updated results from the phase 1 non-enhancing glioma population.

Summary by SW who attended the presentation and took photos of the slides.

Ingo Mellinghoff of Memorial Sloan Kettering Cancer Center presented results of a phase 1 trial of AG-120 (ivosidenib), a mutant IDH1 inhibitor, for IDH1-mutant cancers.  The presentation specifically focused on a subset of patients in the phase 1 trial: those with non-enhancing (no contrast enhancement on MRI images) IDH1-mutant gliomas.  This analysis included 11 patients in the dose escalation phase, and an additional 24 patients from the dose expansion phase, a total of 35 patients.  The primary study objective was to evaluate safety and tolerability of AG-120, and determine the maximum-tolerated dose and/or the recommended phase 2 dose.

28 out of 35 patients (80%) of patients in this analysis were treated with 500 mg of AG-120 daily.  The majority (24/35, or 69%) of patients in this non-enhancing glioma cohort were WHO grade 2 gliomas.  An additional 23% were WHO grade 3.  Only one grade IV glioma (3%) was included.

Most patients in this analysis had been previously treated with either radiation (57%) or chemotherapy (69%) and the median number of prior systemic therapies was 2.

AG-120 was well tolerated, and the maximum tolerated dose was not reached. The majority of adverse events were low grade, and only 20% of patients experienced a grade 3 or higher adverse event. 

Pharmacodynamic analysis of tumor tissue in two patients revealed that AG-120 treatment strongly suppressed 2-hydroxyglutarate levels in the tumors.  2-hydroxyglutarate is the oncometabolite produced by the mutant IDH1 enzyme.

By far the most common response to AG-120 treatment in this cohort was stable disease, which was achieved in 83% of patients. Only two patients (5.7%) achieved a minor response, including one grade 2 and one grade 3 glioma. Only four out of the 35 patients (11%) had progressive disease with neither stabilization or response.  

More important is the duration of stable disease without progression.  Median duration of AG-120 treatment for all 35 patients is 16 months. For the grade 2 gliomas, representing nearly 70% of the population of this study, median progression-free survival has not yet been reached, and looks to be at least 19 months at the time of the analysis (data cutoff May 12 2017).

When volumetric growth rates pre- and post AG-120 treatment were calculated by imaging studies for the 24 patients in the dose expansion group, the mean percentage change in tumor volume per six months was found to be 24% prior to treatment, and 11% after AG-120 treatment.  In the 1p/19q intact (that is, the astrocytoma) subgroup of 15 patients, before and after AG-120 growth rates per six months were 38% and 14%.  This confirms that the primary effect of AG-120 in this group of non-enhancing (mostly) lower grade gliomas is to significantly slow tumor progression, which was deemed to be a disease stabilization in the majority of cases.

A different drug by Agios Pharmaceuticals, called AG-881, is a dual inhibitor of mutant IDH1 and IDH2, is more brain penetrant than AG-120, and is also being studied in clinical trials for IDH mutant gliomas.

SNO summary, episode 1: CeTeG trial (CCNU + TMZ versus TMZ alone)

Phase III trial of CCNU/temozolomide (TMZ) combination therapy vs. standard TMZ therapy for newly diagnosed MGMT-methylated glioblastoma patients: the CeTeG/NOA-09 trial presented by Ulrich Herrlinger for the Neurooncology Working Group (NOA) of the German Cancer Society.

The summary below written by SW, who was in attendance at the presentation by Ulrich Herrlinger and took photos of the slides presented.

The CeTeG trial (also known as NOA-09) is a randomized phase 3 trial for newly diagnosed glioblastoma with methylated MGMT promoter, testing CCNU (lomustine) combined with temozolomide (TMZ) versus TMZ alone. This trial was conducted at 17 centers in Germany and was a follow-up to a non-randomized phase 2 trial which had results published in 2006 and 2009. The CeTeG trial was relatively small for a phase 3 trial, with a sample size calculation of 128 patients total, and this sample size was based on expectations of a significant increase in survival rate at 2 years as seen in the phase 2 trial compared to historical controls. 

Patients in this trial had relatively good prognosis, with high rates of complete resection and high average KPS.  Overall the arms were well balanced, with the only significant imbalance between the two arms being gender, which was not prognostically relevant.

In the combination arm receiving CCNU + TMZ, cycles were 6 weeks in length, with 100 mg/m2 oral CCNU given on day 1 of each cycle and TMZ on days 2-6 of each cycle, with a starting TMZ dose of 100 mg/m2 and possible escalation up to 200 mg/m2 in later cycles. Cycle 1 starts at the same time as radiation.

In the control arm of TMZ alone, cycles were 4 weeks in length, and used the standard TMZ schedule (daily at a dose of 75 mg/m2 during radiation, and 150 mg/m2 on days 1-5 of the first adjuvant cycle and possible escalation up to 200 mg/m2 in later cycles.

Importantly, this trial achieved its primary endpoint of increased overall survival. Survival in the CCNU + TMZ arm was statistically superior to TMZ alone, with a p value of 0.049.  Hazard ratio for death from any cause was 0.6 in the CCNU + TMZ arm.

Median reported survival was 46.9 months for CCNU + TMZ versus 30.4 months for TMZ alone, a difference of 16.5 months.  As seen in the Kaplan-Meier survival estimates, the curves did not separate until after the 2 year mark.  1, 2, 3, 4, and 5 year survival rate was 88.8, 71.4, 57.4, 48.8 and 34% in the CCNU + TMZ arm versus 84.4, 65.4, 42.3, 31.4 and 27.7% in the TMZ arm.  Differences in the survival rate between the two arms were greatest at the 3 and 4 year mark, with 15% more patients surviving to 3 years and 17.4% more patients surviving to 4 years in the combination arm versus the TMZ alone arm.

Given the significant overall survival differences, it's surprising to note that progression-free survival was not significantly different between the two arms (p=0.41), although the progression-free survival curves separated somewhat at about 2 years (a phenomenon also seen in the overall survival curves), after which time CCNU + TMZ shows a slight superiority over TMZ alone. Some potential explanations given by the authors for the lack of a strong PFS signal included: "problems with PFS assessment according to RANO?" including potential undetected pseudoprogressions; and "long-term effects of CCNU?", noting that in studies of low grade gliomas treated with CCNU, responses were sometimes seen months or years after the end of therapy.

  

The percentage of patients receiving further lines of therapy after progression was similar in both arms (59.1% in the CCNU + TMZ arm, 63.5% in the TMZ arm).  More patients underwent re-resection in the CCNU + TMZ arm (31.8% versus 22.2%), and more patients received re-irradiation in the TMZ alone arm (23.8% versus 18.2%). More patients in the TMZ alone arm received further chemo or targeted agent therapy (60.3% versus 48.5%).  The percentage of patients receiving bevacizumab after progression was similar in both arms (27% in the TMZ alone arm, 30.3 % in the TMZ + CCNU arm).  The authors concluded that differences in treatment after progression are not an explanation for the superior survival in the TMZ + CCNU arm.

Combination therapy with TMZ + CCNU approximately doubled the rate of low-grade (but not high-grade) hematoxicity (including neutropenia and thrombocytopenia) and nausea.  However no deaths due to treatment toxicity were observed, and no severe infections, liver failure, or lung fibrosis. More brain edema was observed in the combination arm, and more low-grade alopecia (patchy hair loss).

The authors concluded by noting that acute toxicity of the combination treatment was rare, and importantly, "the primary aim of CeTeG/NOA-09 was achieved: the OS superiority of CCNU/TMZ for MGMT promoter methylated newly diagnosed GBM could be demonstrated".

This may well be the most significant trial outcome reported at the 2017 SNO conference. Since TMZ was approved for newly diagnosed glioblastoma in 2005, it has been exceedingly rare for a phase 3 trial in the newly diagnosed GBM setting to achieve statistically significant prolongation of survival with a novel regimen.  More work needs to be done to explain why progression-free survival benefit was more modest than overall survival benefit in this trial. A potential hypothesis for the improved survival results for the combination therapy is a possible synergistic interaction between TMZ and CCNU, whereby cells escaping sensitivity to TMZ through mismatch repair defects are thereby rendered more sensitive to the CCNU treatment (Stritzelberger et al. 2017). Now that the results of CeTeG have been reported to the international neuro-oncology community, the mechanisms behind the improved outcomes with the combination chemotherapy will likely become the subject of more intense investigation.

SNO conference, San Francisco and Optune compliance

Myself and a friend who also frequents this blog are at this year's SNO conference in San Francisco. I will be reporting on the conference very soon.

To get us started, here is a report from Novocure showing increased survival in the EF-14 trial for patients who achieved 90% or more compliance with Optune (that is to say, wore the Optune device for an average of 90% of the time each day).

Median survival (from randomization, which was 3.8 months after diagnosis), was 21.7 months with 70-80% compliance and 24.9 months with 90% or more compliance.  5-year survival rate in the 90% compliance group was 29.3%.

This dose-response effect is a powerful argument against those who would argue that the positive results in favor of Optune seen in this trial could be a result of a lack of a placebo control, or the result of increased supportive care in the Optune arm.

https://www.novocure.com/patients-who-used-optune-more-than-90-percent-of-the-time-had-the-greatest-chance-of-survival-in-novocures-ef-14-trial-a-median-survival-of-24-9-months-from-randomization-and-a-five-ye/

Disulfiram + copper + radiation + TMZ case report

While not providing definite evidence of disulfiram activity, this case study on the use of disulfiram + copper for an IDH1-mutant, MGMT-unmethylated glioblastoma does show that disulfiram therapy can be initiated at the time of radiation.  The disulfiram dose was 250 mg daily, and the dose of copper gluconate was 3 mg twice daily.

Evidence for the efficacy of disulfiram and copper combinationin glioblastoma multiforme - A propos of a case

First Recurrence, Clinical Trials? No more treatments?

Hello, I have posted before trying to find out more about Val-83 but have not been able to find much information. My husband-unmethylated, IDH Wildtype, no actionable mutations except FIG-ROS1, .51 mutational burden-has had a recurrence and I would appreciate any insights into possible options. 

Quality of life over quantity is our guiding force and I would also appreciate any advice towards not doing any more treatments if you feel that way. My husband keeps saying he has had a great life and he is grateful and if now is his time he is at peace. I, however, am a fixer but I don't want to pressure him into doing things he is not comfortable with and have no proven outcome.

The clinical trial that seems the best suited for Tim is the one for the chemo drug Val-83 at MD Anderson. It is the drug that Al Musella at virtualtrials.com said he would try if he were unmethylated. It is a small molecule drug that was used in the 70s I think. Unfortunately I can find out very little about side effects or benefits. It is Phase 2. We have an appointment with them.

I have also contacted Duke and Dana Farber to see if they have anything to offer. Tim's NO said he was not a good candidate for an immunotherapy, I think because his tumor mutational burden is not high. He is pre-approved for Nivolumab. He probably does not have enough tumor frozen to make a vaccine and his gut reaction is he does not want another surgery plus his NO thinks the new tumor may be too deep and inoperable.

Other choices are the old chemo drugs CCNU/Lomustine. I have also heard of people using it with Avastin concurrently.

A basket drug, entrectinib, I know little about and is not used for GBM but one that could be used because of his FIG-ROS-1 mutation.

Avastin, of course, I hear more good things than bad but am always worried about the worse case scenarios as Tim seems to be sensitive to drugs.

I have also read about 3BP as a miracle drug but don't know if it is even available or if it was just an anomaly or a great story or what?

Thanks, Dianne

Salinomycin

Hi everybody,
Has anyone tried salinomycin infusion for GBM? One clinic offers this protocol, but I only found this article
https://www.ncbi.nlm.nih.gov/pubmed/24351423
Nothing about it in humans, BB barrier, etc.
Hope for us all
Bb

Recurrent Glioma with leptomeningeal spread ?

Hi all,

Thank you for the kind reply on my previous post. Updating on my brother situation (diagnosed GBM March 2016, radiation, temodal, theracim), MRI show spot on February 2017.  He decided to undergo surgery just two weeks ago on 31 October 2017 with mass approx. 1.7cm . What confused us is the laboratory report just out and it stated, 'recurrent glioma, with leptomeningeal spread'. But they cannot decide what grade it is as the cell is too damaged by previous chemoradiation and it is 'too small'. Even the neurosurgeon itself not sure what the conclusion means. Do anyone familiar with this term or understand what it means? as I have searched over the internet but still confused if it is a bad things or just a normal explanation. The laboratory also collect another sample stated as 'Scar' and  'Surrounding Brain' which come out as benign tissue. Thank you for the time and attention.

considering other options

Dear all,
I again need your advice - currently my son (17 , approaching 18) has a recurrence of his H3K27 glioma, "very low methylation" ( a rather strange phrasing of pathology from UPenn. I would still consider it unmethylated like H3K27 gliomas are)  . It is multifocal now and because it involves cerebellum we cant do polio trial or City of Hope Car-T cells. We are currently on Temodar and CCNU and have just finished 10 whole head radiation sessions with Dr.Lederman . We managed to get him ONC 201 earlier, but in September he had bleeding in the brain, so they pulled back ONC201. It was, in my opinion, too early to tell if ONC 201 worked or not. We also had Avastin twice ( before starting ONC201), but our NO won't give Avastn again due to the risk of bleeding. We are also on Keppra and a few CUSP 9 drugs.
We are considering the following options:
1. Just continue with CCNU and Temodar
2. Try getting into adult trial of Val 083 - we had success getting ONC201 being under 18, so we are determined to try getting it now.
3. Try to get ONC 201 again to add to Temodar and CCNU
4. Any other ideas?
I really would appreciate suggestions as to what else we might try - any ideas of other trials? Over the last year we have been completely excluded from any adult trials, but now we are almost at the point where he is almost 18.
Thank you!

Where can we buy methadone without prescription ?

Does anybody know where we can buy methadone without prescription?

Immunotherapy at IOZK Cologne

Hello all,

My 38 year old brother has been diagnosed with a Glioblastoma six weeks ago. Since then he has had total surgical resection and is currently finishing his second week of temodar and radiation. He has also added quite an extensive amount of additional medication as a cocktail approach (I am sure that he will write a more detailed post about the drugs he is taking, when he finds the time). We have found the information in this blog to be extremely helpful. Thanks a lot to Stephen and all of you participating in this great resource.

Right now we are thinking about additional options for the time after his chemo/radiation phase. One thing that we are quite interested in is immunotherapy. Unfortunately my brother’s resected tumor tissue hasn’t been frozen but conserved in paraffin so that options are somewhat limited. We have contacted IOZK in cologne and they have said that they could produce a vaccine without the tumor tissue, using only a blood sample. Cologne is not too far from where we live.

I have read various comments, in this blog, about the IOZK clinic and I know that some of you have been, or have had family members being treated there. I would be very grateful if you could tell me about your experience with the clinic and whether you would recommend giving it a try.

Thanks!

Phil

Surgery, Avastin or Study Drug Abemaciclib ?

My husband (54yr.) is ~12 months post total surgical resection of GBM unmethylated (got standard treatment of radiation, temodar, and additional 1 mo. of  study drug -IV plerixafor-to enhance radiation effects) Over the past 4 months. MRI is showing increased changes that appear to be evolving treatment changes probably from Plerixafor enhancement of radiation  (+ more swelling) and it appears ther could be a small nodule of  GBM tumor recurrence. His symptoms have also increased (some speech stumbling, small focal seizures, plus a grand mal).  Thus he was put on dexamethasone (steriod 4 mg twice daily (now down to 6mg daily)  and increased Keppra from 2000mg daily to 3000mg daily) .  Next the NO wants to start Avastin (the NO is NOT for surgery).  We are trying to decide on a few options and will get one more MRI  and possibly PET CT to see if tumor recurrence is more definitive.

Choices:
1.  If MIR confirms additional growth, then Surgical removal of tumor first (surgeons recommendation)
2.  Avastin for swelling and to shrink tumor and perhaps add on Optune (NO's recommendation)
3.  2nd opinion of NO at UCSF site suggests Study drug Abemaciclib  due to gene testing of my husband's tumor pathology that shows CDKN2A, CDKN2B.  If we take this route then NO AVASTIN can be used.

Trying to figure out best option for highest functioning and quality of life.

Your Thoughts Appreciated.

Clinical Trials for Low KPS recurrent GBM patients

Hi all,

Is anyone aware of any Clinical trials taking place on the West Coast (USA) that consider low KPS recurrent GBM patients?

I've had my eye out for any reasonably non toxic options, but almost all trials have an entering criteria of >60-70kps score even for recurrent patients. My Father is closer to a 50.

I understand why 60/70 kps is standard, I'm just curious if others have heard of non toxic options for patients who cannot fully care for themselves.

We currently take various supplements and THC/CBD oil based on research from this forum, but are always open to more ideas.

My Dads original profile here, although he has since had a recurrence and is no longer taking TMZ:
http://btcocktails.blogspot.com/2017/02/tom-wangerin-cocktail-profile-and.html

Thank you to all

Ari

A few pathology questions and suggestions for course of action on newly diagnosed AA3

My wife(45), in all other aspects healthy and fit, was diagnosed with right temporal  lobe AA3 after >90% resection mid july 2017. Early june she suffered from an epileptic seizure which was the first ever symptom of a tumour  – actually they suspected a rare venous thrombosis for three weeks and treated her as such after first CT/MRI.

Second MRI the mass was constant and they suspected a low grade glioma. MRI Radiologist described it as non- enhancement and welldefined borders 5X3X2cm.
She was transferred to The National University Hospital where we met with the neurosurgeon, who felt sure it was low grade based on the characteristics of the tumour
During surgery frozen sample couldn´t determine grade 2 or 3. Final pathology report concluded grade 3 with the following characteristics (loosely translated from Danish)

Microscopic:

Braintissue with  diffuse infiltrating nature with small microcysts. In areas the tumour has more cell density, the nucleous are light pleomorphic and hyperchromatic – there are mitosis and apoptopsies(?). There is no microvascular carprofilation or necrosis. In the most cell dense areas a moderat high proliferative activity is observed determined by KI67 colouring and up to 6 mitosis per 10/HPF are identified I PHH3 colouring

The tumour tissue is positive in immunestaining for GFA, Maj 2, P53, IDH1 mutation and ATRX mutation

Analysis of  DNA methylation: the average methylation is 33% so methylated MGMT promotor  is found in the analyzed tissue.

The analysis is conducted with pyrosequencing of 4 CpG sites in the MGMT promotor with Therascreen. Cut of value in the analysis is 10%.

MLPA analysis: IDH1 mutation ( c.395>A,p.R123H) has been found in the analyzed tissue. There is no deletion of 1p/19q in the analyzed tissue.

Macroscopic:
Leptomengial sample tissue measuring 34,25,16 mm. Central cut to freeze+ imprint. Freezediagnosis Diffuse glioma grade 2-3. Freeze sample to biobank.

Diagnosis:
Diffuce Astrocytoma and based on proliferative activity classified as Anaplastic Astrocytoma WHO gr III.

1 month after surgery she did 6 weeks of daily TMZ (125mg) and proton treatment weekdays (~59gy). She is now at home with chemo pause until nov 8^th where she will start 6-12 rounds of 300>400mg TMZ by Stupps protocol (5/28). She has no icognitive nor neurologic ssues except for a little mild vertigo at times, which NO suspect to be her Keppra medication.

Question 1:

MRIs were not made within 72 hours post op. MRIs were made on aug 1^st and sept 15^th during proton treatments, but these were merely in regards to tracking the preciseness of the proton treatment. No further feedback except that there was no change between the two scans, but also that it would be impossible to differantiate post-op scartissue, radiation effects and actual tumour at this point. Next scan is scheduled at Jan 4^th. Is that also your experience?

Question 2:

After surgery and pathology neurosurgeons and oncologist all expressed that her tumour was in the greyzone between grade 2 and 3. But as there is limited actual data e.g. “moderate high” rather than percentage of KI67 staining, further genomic data and a relatively high(?) mitosis count is most dense areas it is hard to compare to data in online datasets. Do you have an idea of what they would base their statement on? Is it the IH,MGMT,ATRX combination, the resection degree and relatively welldefined borders or something else?

Question 3:

Based on the latest NOA-9 trial would it make sense to push for a CCNU/TMZ combination instead of Stupps or are the results yet to vague and even untrialed for AA3? What would be the prime candidate for a trial in case of recurrence for a tomour with the above characteristics – Tocagen (good results – 50% or 2/4 - on high dose IDH AAs), DCVAX, MDNA-55 or something else?

DNX-201 With Pembrolizumab (Keytruda)

Hello All,

I am looking for any comments, experience and suggestions with the DNX-2401 trial.

The Phase II just opened and I am enrolled for the procedure on Monday.

My GBM was resected in June 2015 and there has been some mass increases in the area between my cavity and skull.  Shows some signs of tumor and some signs as necrosis.


Of the couple of trial options offered to me, (southern California) these seems like the best, like the biopsy aspect of this trial.

When I asked a GBM research scientist friend of mine, I got the following comment:

Paraphased:

 - DNX-2401 is a one shot try.  If it comes back up the biopsy hole, then nothing is going to happen.

So this makes sense, that if no DNX-201 then nothing for the PD1 to work on.

But is this really a concern?

Any, why cannot you just re-inject if this happens?

Marc

Complete responses in Tocagen phase 1 trial

Tocagen just released data showing that in their phase 1 trial for injection of Toca511 into the resection cavity (NCT01470794), two of the partial responders became complete responders, bringing the total number of complete responses up to 6 out of 56 patients in the trial.  However, in a subanalysis of the higher dose cohorts, 5 out of 23 were complete responders (22% complete response rate).  These responses are also durable, with median duration of response being not yet reached at a median follow up of 35.7 months.

View press release here, and download the full PDF of the presentation here (Oct 27 2017 presentation).

new paper on IDH305, mutant IDH1 inhibitor

abstract on pubmed here

sci-hub download here

Temodar and CCNU

We finally convinced our NO to give our son Temodar and CCNU for his recurrence. Our NO wants to do it every 42 days. However, we are uncomfortable with such long gaps, especially considering his platelets are good. Do you know of any studies with shorter periods between administration that I can refer our doctor to? Thank you !