84 Participants Needed

ONC201 for Brain Tumor

Recruiting at 4 trial locations
SR
EM
DA
RP
Overseen ByRamage, PhD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that you cannot use certain drugs that affect liver enzymes (CYP3A4/5 inhibitors and inducers) during the study and shortly before starting it. It's best to discuss your current medications with the study team to see if any adjustments are needed.

What makes the drug ONC201 unique for treating brain tumors?

ONC201 is unique because it targets a specific pathway in cancer cells, potentially offering a new approach for treating brain tumors that are resistant to standard therapies. Unlike other treatments, it may work by inducing stress in tumor cells, leading to their death, and is being explored for its effectiveness in various types of brain tumors.12345

What is the purpose of this trial?

This trial tests ONC201, a new type of treatment that has shown promise in fighting various cancers, including a specific type of brain cancer, in patients who have this cancer returning.

Eligibility Criteria

Inclusion Criteria

Unequivocal evidence of progressive disease on contrast-enhanced brain computerized tomography (CT) or magnetic resonance imaging (MRI) as defined by Response Assessment in Neuro-Oncology Criteria (RANO), or have documented recurrent glioblastoma on diagnostic biopsy.
Previous first line therapy with at least radiotherapy and temozolomide. For Arms D, E, and F, previous first line therapy with at least radiotherapy
Male or Female age ≥16 years.
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Exclusion Criteria

Pregnant women because ONC201 is novel agent with unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ONC201, breastfeeding should be discontinued if the mother is treated with ONC201.
Known HIV-positive test on combination antiretroviral therapy.
Known history of cardiac arrhythmias including atrial fibrillation, tachyarrhythmias or bradycardia. Receiving therapeutic agents known to prolong QT interval will be excluded. History of CHF, or MI or stroke in the last 3 months will be excluded.
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Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 625 mg oral dordaviprone (ONC201) every 1 or 3 weeks depending on the arm, with clinical evaluations after each cycle

6 months
Every 1 or 3 weeks (in-person)

Neuroimaging

Neuroimaging studies are performed at baseline, 8 weeks from treatment initiation, and then every 8 weeks thereafter

8 weeks
Baseline, 8 weeks, then every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • ONC201
Participant Groups
6Treatment groups
Experimental Treatment
Group I: Arm FExperimental Treatment1 Intervention
Patients had diffuse midline glioma involving the brainstem, thalamus, or spinal cord, without the H3 K27M mutation or with unknown H3 mutation status. Patients received 625 mg dordaviprone (ONC201) weekly (Days 1, 8, and 15 of each cycle).
Group II: Arm EExperimental Treatment1 Intervention
Patients had clinical and/or radiographic evidence of midline glioma (recurrent disease was not required) and were eligible for salvage surgical resection. Patients received 625 mg dordaviprone (ONC201) weekly (Days 1, 8, and 15 of each cycle). Surgical resection was performed approximately 24 hours after at least the second dose of dordaviprone (ONC201).
Group III: Arm DExperimental Treatment1 Intervention
Patients had confirmed World Health Organization Grade IV glioma with H3 K27M mutation (any number of recurrences were allowed). Patients received 625 mg dordaviprone (ONC201) weekly (Days 1, 8, and 15 of each cycle).
Group IV: Arm CExperimental Treatment1 Intervention
Patients had clinical and/or radiographic evidence of first recurrence of histologically confirmed World Health Organization Grade IV glioblastoma and were eligible for salvage surgical resection. Patients received 625 mg dordaviprone (ONC201) weekly (Days 1, 8, and 15 of each cycle). Surgical resection was performed approximately 24 hours after at least the second dose of ONC201.
Group V: Arm BExperimental Treatment1 Intervention
Patients had first recurrence histologically confirmed World Health Organization Grade IV glioma. Patients received 625 mg dordaviprone (ONC201) weekly (Days 1, 8, and 15 of each cycle).
Group VI: Arm AExperimental Treatment1 Intervention
Patients had histologically confirmed World Health Organization Grade IV glioblastoma with any number of recurrences. Patients received 625 mg dordaviprone (ONC201) once every 3 weeks.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Chimerix

Lead Sponsor

Trials
42
Recruited
4,100+

Oncoceutics, Inc.

Industry Sponsor

Trials
10
Recruited
500+

Findings from Research

A study of 159 patients with grade II/III gliomas revealed significant over-expression of specific tumor-associated antigens (BCAN, CSPG4, IGF2BP3, PTPRZ1, and TNC) at both mRNA and protein levels, indicating their potential as targets for immunotherapy.
In a smaller group of 27 patients, spontaneous T cell responses to the IMA950 antigens were detected in all grade II patients and 71% of grade III patients, suggesting that these antigens are relevant for effective tumor targeting and could enhance the efficacy of immunotherapy when combined with other peptides.
Antigenic expression and spontaneous immune responses support the use of a selected peptide set from the IMA950 glioblastoma vaccine for immunotherapy of grade II and III glioma.Dutoit, V., Migliorini, D., Ranzanici, G., et al.[2021]
In a case series of 4 patients with BRAF V600E primary brain tumors, dual therapy with dabrafenib and trametinib led to near-complete or complete clinical responses in three patients after 8 weeks, demonstrating significant efficacy.
The combination therapy not only showed greater effectiveness than dabrafenib alone but also helped reduce skin-related side effects, such as keratosis, highlighting its potential to improve patient tolerability during treatment.
Dual BRAF/MEK therapy in BRAF V600E-mutated primary brain tumors: a case series showing dramatic clinical and radiographic responses and a reduction in cutaneous toxicity.Bernstein, A., Mrowczynski, OD., Greene, A., et al.[2023]
The phase I trial involving 33 patients with IDH1(R132H)+ astrocytomas demonstrated that the IDH1-specific peptide vaccine was safe, with only grade 1 adverse events reported, and induced immune responses in 93.3% of participants.
Patients who developed immune responses to the vaccine had significantly better outcomes, with a two-year progression-free rate of 0.82, compared to those without immune responses, highlighting the vaccine's potential efficacy in treating this specific type of glioma.
A vaccine targeting mutant IDH1 in newly diagnosed glioma.Platten, M., Bunse, L., Wick, A., et al.[2022]

References

Antigenic expression and spontaneous immune responses support the use of a selected peptide set from the IMA950 glioblastoma vaccine for immunotherapy of grade II and III glioma. [2021]
Dual BRAF/MEK therapy in BRAF V600E-mutated primary brain tumors: a case series showing dramatic clinical and radiographic responses and a reduction in cutaneous toxicity. [2023]
A vaccine targeting mutant IDH1 in newly diagnosed glioma. [2022]
Dabrafenib Treatment in a Patient with an Epithelioid Glioblastoma and BRAF V600E Mutation. [2022]
INTERCEPT H3: a multicenter phase I peptide vaccine trial for the treatment of H3-mutated diffuse midline gliomas. [2023]
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