ONC201 and Radiation Therapy Before Surgery for the Treatment of Recurrent Glioblastoma

NCT04854044 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: 21-000054NCI-2021-02121P50CA211015
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the effects of ONC201 in combination with standard of care radiation therapy in treating patients with glioblastoma that has come back (recurrent). ONC201 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy photons to kill tumors cells and shrink tumors. Giving ONC201 in combination with radiation therapy may help treat patients with recurrent glioblastoma.

Conditions

Recurrent Glioblastoma; Recurrent Gliosarcoma; Recurrent Supratentorial Glioblastoma; Supratentorial Gliosarcoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

  Up to 90 days after the last study treatment

• Percentage of neurosphere formation

  A two-sample two-sided t-test will be performed to compare the percentage of neurosphere formation of treated brain tumor tissues and non-treated brain tumor tissues.

  At the tumor resection during surgery

Secondary Outcomes (2)

• Expression of glioma stem cells using ribonucleic acid-sequencing (RNA-Seq)

  At the tumor resection during surgery

• Pharmacodynamic (PD) markers

  At the tumor resection during surgery

Other Outcomes (5)

• Progression-free survival

  Up to 4 years

• Overall survival

  Up to 4 years

• Pharmacodynamic markers

  At the tumor resection during surgery

Study Arms (2)

Arm I (ONC201, radiation therapy, resection)

EXPERIMENTAL

Patients undergo radiation therapy for 10 fractions over 2 weeks, and receive ONC201 PO daily on days 1, 2, 8, and 9. Beginning 24 hours after completion of radiation therapy, patients undergo surgical resection. Beginning 7 days from last pre-surgery dose of ONC201, patients receive ONC201 PO daily on two consecutive days weekly (2 days on/5 days off) in the absence of disease progression or unacceptable toxicity.

Drug: Akt/ERK Inhibitor ONC201; Radiation: Radiation Therapy; Procedure: Resection

Arm II (ONC201, radiation therapy, resection)

EXPERIMENTAL

Patients undergo radiation therapy for 10 fractions over 2 weeks. Beginning 24 hours after completion of radiation therapy, patients undergo surgical resection. After recovery from surgery, patients receive ONC201 PO daily on two consecutive days weekly (2 days on/5 days off) in the absence of disease progression or unacceptable toxicity.

Drug: Akt/ERK Inhibitor ONC201; Radiation: Radiation Therapy; Procedure: Resection

Interventions

Akt/ERK Inhibitor ONC201 DRUG

Given orally

Also known as: ONC201, TIC10

Arm I (ONC201, radiation therapy, resection); Arm II (ONC201, radiation therapy, resection)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Arm I (ONC201, radiation therapy, resection); Arm II (ONC201, radiation therapy, resection)

Resection PROCEDURE

Undergo surgical resection

Also known as: Surgical Resection

Arm I (ONC201, radiation therapy, resection); Arm II (ONC201, radiation therapy, resection)

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically proven glioblastoma or gliosarcoma which is progressive or recurrent following radiation therapy +/- chemotherapy
• Participants must have evaluable, supratentorial contrast-enhancing progressive or recurrent glioblastoma or gliosarcoma by magnetic resonance imaging (MRI) imaging within 14 days of study treatment initiation. Participants must be able to tolerate MRIs
• Participants can have any number of prior relapses
• Participants must have recovered from severe toxicity of prior therapy. The following intervals from previous treatments are required to be eligible:
• weeks from the completion of radiation
• weeks from a nitrosourea chemotherapy or mitomycin C
• days from temozolomide chemotherapy
• weeks from other cytotoxic therapy unless noted above
• weeks or 5-half-lives (whichever is shorter) from any other investigational (not Food and Drug Administration \[FDA\]-approved) agents (including vaccines)
• Participants must be undergoing surgery that is clinically indicated as determined by their care providers. Patients must be eligible for surgical resection with the expectation that the surgeon is able to resect at least 300 mg of tumor with low risk of inducing neurological injury
• Participants must be undergoing radiotherapy that is clinically indicated as determined by their care providers. The field of radiation must overlap the area of tumor planned for surgical resection. Participants must have a minimum tumor size of 2 x 2 cm\^2 based on MRI scan prior to surgery
• Participants must be 18 years of age or older
• Participants must have a Karnofsky performance status \>= 60% (i.e. the participant must be able to care for himself/herself with occasional help from others)
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL

You may not qualify if:

• Participants receiving any other investigational agents or using an investigational device are ineligible
• Participants with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201 are ineligible
• Participants may not have had prior treatment with ONC201
• Participants may have had prior treatment with bevacizumab/VEGFR inhibitors, but last dose of treatment must be at least 4 weeks prior to the date of planned tumor resection
• Participants may not be on concurrent treatment with Optune device. Prior use of the device is allowable
• Participants must not have evidence of significant hematologic, renal, or hepatic dysfunction
• Participants with a history of any of the following within the last 6 months prior to study entry are ineligible:
• Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
• Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures
• Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)
• Placement of a pacemaker for control of rhythm
• New York Heart Association (NYHA) class III or IV heart failure
• Participants with known significant active cardiovascular or pulmonary disease at the time of study entry are ineligible
• Participants receiving therapeutic agents known to prolong QT interval will be excluded. Patients on sertraline which has the conditional risk of prolonging the QT interval will be allowed on study if they hold sertraline on the day of ONC201 administration
• Participants using concomitant CYP3A4/5 inhibitors within 72 hours prior to starting study drug administration are ineligible

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Oncoceutics, Inc.: collaborator
• University of California, Los Angeles: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

TIC10 compound; Radiotherapy; Radiation

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

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Study Officials

• Phioanh Nghiemphu

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2021
• First Posted: April 22, 2021
• Study Start: May 1, 2021
• Primary Completion: July 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: May 12, 2021

Record last verified: 2021-03

Locations

US (1)