Evaluation of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma

Orbus Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Glioblastoma; Glioblastoma Multiforme; Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype; Glioblastoma, IDH-wildtype; GBM

Treatments: Drug: Temozolomide; Drug: Eflornithine (Dose Level 2); Drug: Eflornithine (Dose Level -1); Drug: Eflornithine (Dose Level 1)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05879367

OT-21-101

Details and patient eligibility

About

The purpose of this study is to establish the recommended phase 2 dose of eflornithine in combination with temozolomide in patients whose glioblastoma is newly diagnosed, and to evaluate safety and tolerability of this combination at that dose.

Full description

This open label dose escalation and expansion study will be conducted using a standard dose-escalation design with escalating doses of eflornithine plus temozolomide at the approved dose level, followed by an expansion cohort that will further evaluate safety and preliminary efficacy of the combination at the recommended phase 2 dose.

Duration of participation will be up to 56 weeks in total per patient:

Screening Period - A maximum screening duration of 4 weeks.

Treatment Period - Up to 48 weeks.

Follow-Up Visit - 4 weeks from last treatment.

A total of up to 66 patients will be enrolled in a non-randomized fashion (patients may be added to any of the dose levels below the RP2D to a maximum of approximately 20 per dose level with the intent of further characterizing safety and pharmacokinetics).

Enrollment: 66 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of World Health Organization (WHO) G4 classified GBM, IDH-wildtype per WHO 2021 tumor classification.
• Completed external beam radiation therapy per standard of care.
• Must have received at least 80% of planned daily doses of TMZ during chemoradiation.
• 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 for GBM other than temozolomide during external beam radiation therapy.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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66 participants in 3 patient groups

Eflornithine Dose Level 1 + Temozolomide

Experimental group

Treatment:

Drug: Eflornithine (Dose Level 1)

Drug: Temozolomide

Eflornithine Dose Level 2 + Temozolomide

Experimental group

Treatment:

Drug: Eflornithine (Dose Level 2)

Drug: Temozolomide

Eflornithine Dose Level -1 + Temozolomide

Experimental group

Treatment:

Drug: Eflornithine (Dose Level -1)

Drug: Temozolomide