Combining eflornithine and temozolomide for newly diagnosed glioblastoma

An Open-label, Phase 1b Study to Evaluate the Safety and Tolerability of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma or Astrocytoma

This study is testing a new combination of two medications, eflornithine and temozolomide, to find the best dose for people with newly diagnosed glioblastoma.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Orbus Therapeutics, Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation
• Locations: 8 sites (Birmingham, Alabama and 7 other locations)
• Trial ID: NCT05879367 on ClinicalTrials.gov

What this trial studies

This interventional phase 1 trial aims to determine the recommended phase 2 dose of eflornithine when used in combination with temozolomide for patients with newly diagnosed glioblastoma. The study employs a dose escalation design, where patients will receive escalating doses of eflornithine alongside a standard dose of temozolomide. Following the dose escalation, an expansion cohort will further assess the safety and preliminary efficacy of the combination at the recommended dose. Participants will be monitored over a total duration of up to 56 weeks, including treatment and follow-up periods.

Who should consider this trial

Good fit: Ideal candidates include patients with newly diagnosed, IDH-wildtype glioblastoma who have completed standard radiation therapy and received adequate doses of temozolomide.

Not a fit: Patients with recurrent or metastatic cancer, prior systemic chemotherapy for glioblastoma, or significant uncontrolled medical conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could improve treatment outcomes for patients with glioblastoma.

How similar studies have performed: While this approach is novel in combining eflornithine with temozolomide, similar studies have shown promise in glioblastoma treatment with other combinations.

Eligibility criteria

Inclusion Criteria:

* Diagnosis of World Health Organization (WHO) G4 classified GBM, IDH-wildtype (patients with GBM) or G3 astrocytoma (IDH1 or 2 mutant; CDKN2A/B intact) per WHO 2021 tumor classification.
* Completed external beam radiation therapy per standard of care.
* Patients with GBM: Must have received at least 80% of planned daily doses of TMZ during chemoradiation. Patients with astrocytoma: Must have tolerated adjuvant TMZ treatment through at least 2 and not more than 4 cycles.
* Adequate hematologic, renal, hepatic, and other organ function as indicated by hematology and serum chemistry testing.
* Willing to abstain from intercourse or use acceptable contraceptive methods.
* If taking corticosteroids, must be on a stable or decreasing dose.

Exclusion Criteria:

* Recent history of recurrent or metastatic cancer that could confound response assessments
* Prior systemic chemotherapy other than temozolomide during external beam radiation therapy (for patients with GBM) or adjuvant temozolomide through up to 4 pre-study cycles (for patients with astrocytoma).
* Prior Optune treatment.
* Active infection or serious intercurrent medical illness.
* Poorly controlled seizures.
* Significant cardiac disease within 6 months of enrollment.
* Poorly controlled diabetes.
* Use of another investigational agent within 30 days of enrollment.

Where this trial is running

Birmingham, Alabama and 7 other locations

• University of Alabama at Birmingham — Birmingham, Alabama, United States (Withdrawn)
• Henry Ford Hospital — Detroit, Michigan, United States (Recruiting)
• Columbia University Medical Center - Herbert Irving Pavilion — New York, New York, United States (Recruiting)
• Duke University — Durham, North Carolina, United States (Recruiting)
• The Cleveland Clinic — Cleveland, Ohio, United States (Recruiting)
• Brown University Health/Rhode Island Hospital — Providence, Rhode Island, United States (Recruiting)
• UT MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• University of Utah, Huntsman Cancer Institute — Salt Lake City, Utah, United States (Recruiting)

Study contacts

• Principal investigator: Howard Colman, MD, PhD — Huntsman Cancer Institute/ University of Utah
• Study coordinator: Monika Varga

Conditions Glioblastoma, IDH-wildtype; Glioblastoma; Glioblastoma Multiforme; Glioblastoma IDH Wildtype; GBM; Astrocytoma; Astrocytoma, IDH-Mutant