Michael Mosier Defeat DIPG Foundation and The ChadTough Foundation, with their chapters and partner families, have granted over $600,000 for the Diffuse Midline Glioma – Adaptive Clinical Trial (DMG-ACT), a new collaboration through the Pacific Pediatric Neuro-Oncology Consortium (PNOC) and the DIPG Centre of Expertise in Zurich.
This innovative project will support preclinical and clinical work across multiple institutions to move combination therapies for DIPG into the clinic as quickly as possible. Scientists across the world will share their latest preclinical data, greatly enhancing opportunities for research impact and improved patient outcomes.
The DMG-ACT is an international, adaptive clinical trial for diffuse midline gliomas. DMGs are fast-growing, cancerous tumors found in the midline of the brain, and they include diffuse intrinsic pontine glioma (DIPG) tumors.
“We’ve developed a clinical trial protocol, with multiple arms, where we will use evidence from multiple labs to bring the best combination therapies forward,” says Dr. Sabine Mueller, pediatric neuro-oncologist of University of California, San Francisco and Clinical Program Head at DIPG Centre of Expertise in Zurich. “Initially, our main concern is if drugs are really getting into the tumor of these devastating diffuse midline gliomas. If we do not see any early signs of survival impact, we will also look at drug penetration to decide if an arm should be adjusted or closed.”
The other key focus of this program will be to offer combination therapies at each stage of the disease (newly diagnosed, post-radiation, and upon recurrence). In addition to new promising combinations, many critical studies will be performed (biopsies, blood draws, and lumbar punctures) for real-time analysis at labs around the world to learn which treatments are working and why. This trial setup is unprecedented for pediatric diffuse midline glioma.
“PNOC has a very well organized and motivated clinical trial infrastructure in San Francisco and Zurich that allows trials to open quickly, complete quickly, and share data quickly. This allows us to speed up translating discoveries in the lab to the bedside and share our data with colleagues around the world in real time,” said Michigan Medicine pediatric oncologist Dr. Carl Koschmann, who serves as a PNOC site co-principal investigator. PNOC is an international consortium with study sites within the United States, Canada, Europe and Australia.
Like many PNOC trials, DMG-ACT will require or offer sequencing along with the therapy, depending on the diagnosis. This data will be deposited into a central PNOC database that allows researchers within and outside of PNOC to access de-identified data. Researchers will then be able to work together to design the future generation of trials while also re-evaluating current trials.
The protocol for DMG-ACT is different from typical clinical trials in that it studies smaller groups of patients (15 to 20). Patients are then added or transitioned to other treatments based on initial findings. This design allows the trial to proceed much quicker than typical early-phase clinical trials.
As part of this trial, a consortium of more than 10 international labs (the DMG-ACT Pre-Clinical Team) has been studying single and combinatorial treatments on models of DMG. This data is then shared with the DMG-ACT Clinical Team. The drugs that are the most promising pre-clinically are then selected for use in combination in an arm of DMG-ACT. Once selected, the Pre-Clinical Team works to develop markers of treatment response to look for in the tissue and liquid samples that clinicians will collect from patients.
Researchers at PNOC are currently finalizing the protocol and agreement with sponsors of the initial combinations. The first arm of the trial should be open for enrollment early fall 2020 and includes the combination of ONC201 and panobinostat.
“Simply put,” said Dr. Koschmann, “the trial would not be opening this year without the current and future support of Michael Mosier Defeat DIPG Foundation and The ChadTough Foundation. Their early and generous support of DMG-ACT allowed us to remove all brakes to get all aspects of the infrastructure created and get the trial open, with the international scale of pre-clinical and clinical aspects we felt our patients needed. For those of us involved with this trial, we feel this is the trial that will finally provide the jumps in improved survival for DMG that was seen in leukemia 40 to 50 years ago. It is fitting that Michael Mosier Defeat DIPG Foundation and The ChadTough Foundation are part of our team for this.”
Frequently Asked Questions
Q: When will the trial open for enrolling patients?
We are currently estimating that the trial will be finalized in Fall 2020. The earliest site openings are expected in late 2020, with broader openings in 2021.
Q: How can I find out if my child qualifies for this trial?
Q: What can I do to be ready to enroll when the trial opens?
When the trial opens, patients (or their parents) may contact their nearest PNOC site, and let them know you would like to be considered for the DMG-ACT trial PNOC sites are listed at www.pnoc.us, or email PNOC at PNOC_Regulatory@ucsf.edu for further details.
Q: My child is currently enrolled in a different trial. Can I switch to DMG-ACT so my child can get a combination therapy?
There are three cohorts to the trial in its current form: (1) newly diagnosed (before radiation), (2) post-radiation (before progression), and (3) at progression/relapse. It is less likely that a patient would be eligible for one of these cohorts if currently on a clinical trial without progression.
Q: Is it possible for my child to be involved in the trial, yet receive treatments at our own cancer center?
Treatment/enrollment will only be through PNOC sites. It is possible that some of the care can be performed locally.
Q: Will there be a required washout period before starting the trial?
Yes, washout periods will be similar to other clinical trials and will depend on which arm you enroll.