A Phase II, Open Label Study of ONC201 in Adults With EGFR-low Glioblastoma

NCT04629209 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: 2020LS093ONC026
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, two arm study. The trial will enroll a total of up to 36 patients. Arm A will enroll up to a total of 6 evaluable patients and Arm B will enroll up to a total of 30 evaluable patients. Arm A will explore the intra-tumoral ONC201 concentrations and pharmacodynamic activity in adult EGFR-low glioblastoma patients. Arm B will determine the radiographic efficacy of ONC201 in adult recurrent EGFR-low glioblastoma patients. All patients will be treated with oral ONC201 (625 mg) twice weekly, 2 consecutive days on and 5 days off per week schedule.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Intra-tumoral ONC201 concentrations

  intra-tumoral ONC201 concentrations in adult EGFR-low glioblastoma patients. The drug concentrations will be measured in micrograms per milliliters.

  11 Days

• Objective Response Rate

  Objective Response Rate of ONC201 in adult recurrent EGFR-low glioblastoma patients. Measured using the RANO criteria.

  6 months

Study Arms (2)

Arm A: ONC201 with Surgical Resection in Glioblastoma

EXPERIMENTAL

Patients must be eligible for salvage surgical resection as deemed by the site Investigator. ONC201 will be administered orally, twice a week (2 consecutive days on and 5 days off per week) schedule at a dose of 625mg.

Drug: ONC201

Arm B: ONC201 in Glioblastoma

EXPERIMENTAL

Unequivocal evidence of recurrence (progressive disease) on contrast-enhanced brain CT or MRI as defined by RANO criteria, or have documented recurrent glioma on diagnostic biopsy. ONC201 will be administered orally, twice a week (2 consecutive days on and 5 days off per week) schedule at a dose of 625mg.

Drug: ONC201

Interventions

ONC201 DRUG

ONC201 is a orally active, small molecule DRD2 antagonist that kills cancer cells but not normal cells.

Arm A: ONC201 with Surgical Resection in Glioblastoma; Arm B: ONC201 in Glioblastoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have histologically confirmed World Health Organization Grade IV glioblastoma.
• Patient must have all of the following in their most recently resected archival tumor tissue: (1) absence of EGFR gene amplification by FISH, (2) absence of EGFRvIII expression by RT-PCR, and (3) low EGFR expression by IHC.
• For Arm A: Patients must be eligible for salvage surgical resection as deemed by the site Investigator.
• For Arm B: Unequivocal evidence of recurrence (progressive disease) on contrast-enhanced brain CT or MRI as defined by RANO criteria, or have documented recurrent glioma on diagnostic biopsy.
• Patient must have measurable disease by RANO criteria.
• Patient must have had previous therapy with at least radiotherapy.
• Patient must have an interval of at least 90 days from the completion of radiotherapy prior to the first dose of ONC201. If patients are within 90 days of radiotherapy, they may still be eligible if they meet one or more of the following criteria.
• Progressive tumor is outside the original high-dose radiotherapy target volume as determined by the treating investigator, or
• Histologic confirmation of tumor through biopsy or resection, or Nuclear medicine imaging, MR spectroscopy, or MR perfusion imaging consistent with true progressive disease, rather than pseudoprogression or radiation necrosis, obtained within 28 days of registration.
• From the projected start of ONC201, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies.
• All adverse events Grade \> 1 related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must be resolved to grade 1 or baseline, except for alopecia and sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment, are acceptable.
• Patient must be ≥18 years of age.
• Patient must have a Karnofsky Performance Status (KPS) ≥ 60
• Patient must have adequate organ and marrow function as defined below, all screening labs should be performed within 14 days of treatment initiation:
• leukocytes ≥ 3,000/mcL

You may not qualify if:

• Patient has a midline glioma.
• Patient has a known histone H3 K27M mutation.
• Patient has a known IDH1 (isocitrate dehydrogenase 1) or IDH2 mutations or 1p/19q co-deletion.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201 or its excipients (See Section 8).
• Presence of diffuse leptomeningeal disease or evidence of CSF dissemination.
• Current or planned participation in a study of an investigational agent or using an investigational device.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
• Active infection requiring systemic therapy.
• Pregnant and/or breastfeeding women or unable to maintain use of contraception while on study and for 30 days after the last dose of study drug.
• Known HIV-positive test on combination antiretroviral therapy.
• Known history of cardiac arrhythmias including atrial fibrillation, tachyarrhythmias or bradycardia, unless arrhythmia is controlled and after Cardiology has cleared patient to receive ONC201.
• History of CHF, or MI or stroke in the last 3 months.
• Receiving therapeutic agents known to prolong QT interval.
• Active illicit drug use or diagnosis of alcoholism that would interfere with study compliance or the assessment of outcomes.
• Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ melanoma, or in situ cervical cancer that has undergone potentially curative therapy.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• University of Minnesota: collaborator

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

TIC10 compound

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: November 10, 2020
• First Posted: November 16, 2020
• Study Start: June 28, 2024
• Primary Completion: December 31, 2024
• Study Completion: June 30, 2025
• Last Updated: November 24, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)