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Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms

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ClinicalTrials.gov Identifier: NCT04541082
Recruitment Status : Recruiting
First Posted : September 9, 2020
Last Update Posted : March 2, 2022
National Institutes of Health (NIH)
Information provided by (Responsible Party):

Brief Summary:
The primary objective of this phase 1 trial is to determine the maximum tolerated dose (MTD), food effect, safety and tolerability of oral ONC206 in patients with recurrent, primary CNS neoplasms.

Condition or disease Intervention/treatment Phase
Central Nervous System Neoplasms Glioblastoma Gliosarcoma, Adult Anaplastic Oligodendroglioma Anaplastic Astrocytoma Pilocytic Astrocytoma Oligodendroglioma Gliomatosis Cerebri Pleomorphic Xanthoastrocytoma Anaplastic Pleomorphic Xanthoastrocytoma Diffuse Midline Glioma, H3 K27M-Mutant Ependymoma Ependymoma, Anaplastic Medulloblastoma Teratoid Rhabdoid Tumor Neuroectodermal Tumors, Primitive Neuroectodermal Tumors Anaplastic Meningioma Atypical Meningioma Choroid Plexus Neoplasms Pineal Tumor Diffuse Astrocytoma Glial Tumor Drug: ONC206 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A First-in-human Phase I Single-agent Dose-escalation, Food Effect and Dose Expansion Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms
Actual Study Start Date : October 26, 2020
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : February 2025

Arm Intervention/treatment
Experimental: ONC206 Drug: ONC206
ONC206 is a member of the imipridone class of anti-cancer small molecules that share a unique tri-heterocyclic core chemical structure and target G protein-coupled receptors

Primary Outcome Measures :
  1. Maximum Tolerated Dose [ Time Frame: 28 Days ]
    To determine the MTD of single agent oral ONC206

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age ≥ 18 years with a recurrent, primary CNS neoplasm. Primary CNS neoplasms included in this study: glioblastoma and glioblastoma histologic subtypes, gliosarcoma, primary CNS sarcomas, anaplastic glial neoplasms including anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed neuronal-glial tumors, and pilocytic astrocytoma with anaplastic features, diffuse astrocytoma, oligodendroglioma, gliomatosis cerebri, pleomorphic xanthoastrocytoma, anaplastic pleomorphic xanthoastrocytoma, diffuse midline gliomas and histone mutated gliomas, ependymoma, anaplastic ependymoma, and all ependymoma subtypes, medulloblastoma and all medulloblastoma subtypes, atypical teratoid/rhabdoid tumor, primary CNS embryonal/primitive neuroectodermal tumors, atypical and anaplastic meningiomas, choroid plexus tumors, and pineal region tumors.
  • Patients must have recurrent and measurable disease as defined by RANO criteria, using either the HGG and/or low-grade glioma (LGG) RANO criteria based on tumor type, after having received established standard of care treatment for their disease and have no standard treatment options available as determined by the investigators.
  • There is no limit on the number of total recurrences or prior therapies. However, prior therapies with known clinical benefit (including radiation) for specific tumor types are required. Karnofsky Performance Score (KPS) of greater than or equal to 70.
  • Washout for prior investigational or approved cytotoxic chemotherapy is 28 days prior to the first dose of ONC206; 42 days in the case of nitrosoureas; 28 days or 5 half-lives (whichever is less; but not less than 14 days) in case of investigational or approved molecularly targeted agent; 14 days in the case of radiotherapy.
  • Patients will be required to enroll on the NCI Neuro-Oncology Branch natural history study (16-C-0151).
  • No major surgery in the prior 4 weeks
  • Patients must have normal organ and marrow function
  • An available tumor specimen (paraffin-embedded block and/or frozen tissue) from prior resection or biopsy, ≥15 unstained slides for IHC analysis.
  • Ability to swallow oral capsules.
  • Ability to tolerate an MRI study with intravenous gadolinium contrast.
  • Patients must be fully vaccinated for coronavirus disease 2019 (COVID-19), as defined by the Center for Disease Control guidance for patients who are immunocompromised. Patients must have received required vaccination(s) by the time of signing consent and be considered fully immunized (typically 2 weeks after final vaccination) by the first dose of study drug (Cycle 1, Day 1).
  • Patients must have a negative COVID-19 test within 72 hours of the first dose of study drug (Cycle 1, Day 1).
  • Patients must agree to follow study site requirements to limit transmission of COVID-19, such as wearing masks, social distancing, and maintaining good hand hygiene even after vaccination.

Exclusion Criteria:

  • Known HIV-positive test on combination antiretroviral therapy
  • Active cardiac disease
  • Ischemic or hemorrhagic stroke in last 3 months
  • Refractory epilepsy and patients with primary or secondarily generalized seizures in the 28 days before enrollment are excluded. Peri-operative seizures occurring within 7 days of surgery with resolution by day 8 after surgery are allowable. Patients must be on stable doses of one or two seizure medications for 14 days prior to study enrollment.
  • Impairment of gastrointestinal (GI) function
  • Patients who have been treated with any hematopoietic colony-stimulating growth factors (CSFs) (e.g., granulocyte-CSF, granulocyte-macrophage-CSF) ≤2 weeks prior to starting study drug.
  • Concurrent use of warfarin sodium or other Coumadin-derivative anti-coagulants.
  • Concurrent use of strong inhibitors or inducers of CYP3A4, 2D6, 1A2, 2C9 and 2C19 are excluded at least 14 days prior to and throughout the study.
  • Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, or men who do not agree to use highly-effective contraception during treatment and for 16 additional weeks after the final dose of study drug.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04541082

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Contact: Chappell, PharmD 919-806-1074 clinicaltrials@chimerix.com
Contact: Tarapore, PhD 919-806-1074 clinicaltrials@chimerix.com

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United States, Maryland
National Institutes of Health Recruiting
Bethesda, Maryland, United States, 20892
Contact: Referrals    240-760-6010    NCINOBReferrals@mail.nih.gov   
Contact: Kelly Mentges, RN    240-760-7126    kelly.mentges@nih.gov   
Sponsors and Collaborators
National Institutes of Health (NIH)
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Principal Investigator: Mark Gilbert, MD National Institutes of Health (NIH)
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Chimerix
ClinicalTrials.gov Identifier: NCT04541082    
Other Study ID Numbers: ONC206-001
NIH 20C0069 ( Other Identifier: National Institutes of Health )
First Posted: September 9, 2020    Key Record Dates
Last Update Posted: March 2, 2022
Last Verified: February 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Chimerix:
Anaplastic Astrocytoma
Anaplastic Oligodendroglioma
Diffuse Astrocytoma
Additional relevant MeSH terms:
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Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Rhabdoid Tumor
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Choroid Plexus Neoplasms
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Vascular Tissue
Meningeal Neoplasms
Neoplasms by Site
Nervous System Diseases
Neoplasms, Complex and Mixed
Brain Neoplasms
Brain Diseases
Central Nervous System Diseases
Cerebral Ventricle Neoplasms