Thank you Stephen for setting me up on this site.
We are evaluating clinical trials to select one for my mother's GBM treatment. She has not yet started on radiation and Tamodar after the surgery.
Does anyone on this forum have experience with ICT-107 vaccine (randomized with 50% placebo) or DC Vaccine (phase 1) or stem cell based protocol (personalized by UCSF)? We have to choose one of these three this week itself as it's bee 4 week since her surgery and we are running out of time. Any insights or pointers to help select one would be highly appreciated.
1)
Phase 3 Randomized, Double-blind, Controlled Study of ICT-107 in Glioblastoma
2)
Phase I Study of a Dendritic Cell Vaccine for Patients With Either Newly Diagnosed or Recurrent Glioblastoma
3)
An ex USCF doctor has offered to work with us on developing cell based high throughput cancer stem cell protocol.
I would go with ICT-107. The phase I of this vaccine trial had promising results even though phase II had disappointing results. It is a Phase III for a reason and it allows her as newly diagnosed to still get standard of care: temodar and radiation. I once spoke with a lady whose mother stayed clear and was one of the initial patients in phase I of this trial. Can't remember how many years but if I am not mistaken 4/5 years. The cedar Sinai vaccine is phase I so there is less data around it.
ReplyDeleteI am not see I understand option 3.
Best of luck with your choice. May we all be guided to make the right decisions for our loved ones.
The third option (above) would be this trial:
ReplyDeletehttps://clinicaltrials.gov/ct2/show/NCT02654964
Cancer Stem Cell High-Throughput Drug Screening Study
I'd agree with Noha that ICT-107 has the best current supporting evidence out of those 3 options. Although the phase 2 results were not as impressive as the phase 1 results, they were still quite impressive for the subgroup of patients that were HLA-A2 positive and MGMT methylated. Because of this phase 2 finding, only HLA-A2 positive patients are being recruited for phase 3.
Results from phase 2 have been especially impressive in the HLA-A2 positive, MGMT-methylated subgroup: median progression-free survival nearly tripled from 8.5 months in the placebo group to 24.1 months in the ICT-107 group (measured from randomization post-radiation). Median overall survival was not reached in this ICT-107 group in the last report that I've seen.
For the HLA-A2 positive, MGMT-unmethylated group, results were not as dramatic but there was still improvement versus the placebo group: an approximately 4 month improvement in both median progression-free and median overall survival, which were both higher than expected for this subpopulation.
The main drawback of this trial is possible randomization to the standard-of-care + placebo arm, and only patients whose blood tests positive for the HLA-A2 subtype are eligible.
The other two trials mentioned are still early stage, and have not yet published results that I know of.
I would try find out if your mother is positive or negative for HLA-A2, and if negative there would be no reason for further consideration of ICT-107. This testing would be done during eligibility screening for the ICT-107 trial.
There are a whole series of DC trials where people use tumor-derived proteins instead of peptides like in the ICT-107. Advantage is that one is not restricted to HLA phenotype. Proteins also cover more antigens (known antigens but even also unknown antigens particular for that tumor) than a fixed panel of peptides. A further advantage, which is not broadly known yet, is that you can make these tumor-derived proteins very potent tumor antigens, like has been published very recently in Onco-immunology and in Science Translational Medicine. Because of its induction of Immunogenic Cell Death (known in the literature as ICD), one can add to this intervention also ICD-inducing virusses like Newcastle Disease Virus, in order to make a highly immunogenic antigenic status. With such multimodal approach, one stimulates the immune system against the tumor within the body using an in vivo route (Virla therapy) combined with an ex vivo route (injection of ex vivo produced active specific tumor vaccines).
ReplyDeleteHi all -- We missed out on timing for ICT-107 as they had strict criteria. And we also decided against randomized placebo issue (which is unfair for such a disease). Is there a way to get off-the-label vaccines? For example, Rintega for patients with EGFR positive. I am going to enquire with German clinics that Stephen has posted on this site. There seems to be one in Tijuana as well in Mexico.
ReplyDeleteFor anyone with newly diagnosed GBM, I recommend checking pre-surgery trials registration such as DCVax-L or Stem-cell based protocol as they need fresh live tumor extract. We missed out on those as we were not made aware of pre-registration/etc.
Hi Jinesh, did you miss on it because of the HLA positive requirement? If your mother hasn't started treatment, check the NIH clinical trials. They have radiation +temodar+ nivolumab clinical trial. You won't pay anything and they would cover your travel. I am not sure where your mother resides or if she will be able to travel. The trial is also multi site so you might find it in other places. Best of luck with your choices.
ReplyDeleteHi Noha,
ReplyDeleteShe lost movement in her left leg and hand after surgery. So we went there with her in wheelchair. They asked her to walk, which she could not ofcourse. So they did not accept the application. We just started her radiation 2 days ago after tiring out of inquiries into trials available in West coast. Two of them said they wanted fresh live tumor; another one said that spots were filled up; and the one above said no as she could not walk.
Should I have insisted or pushed more?