Evaluation of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma or Astrocytoma

Phase 1

Recruiting

• Conditions: Glioblastoma, IDH-wildtype; Glioblastoma; Glioblastoma Multiforme; Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype; GBM; Astrocytoma; Astrocytoma, IDH-Mutant
• Interventions: Drug: Eflornithine (Dose Level 2); Drug: Eflornithine (Dose Level 1); Drug: Eflornithine (Dose Level -1); Drug: Temozolomide

• Registration Number: NCT05879367
• Lead Sponsor: Orbus Therapeutics, Inc.

Brief Summary

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

Detailed 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 approximately 104 weeks in total per patient.

Screening Period - A maximum screening duration of 4 weeks.

Treatment Period - Up to approximately 104 weeks.

Follow-Up Visit - 4 weeks from last treatment.

Long-term Survival Follow-Up - up to 2 years 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).

Study Timeline

• Study First Submitted: 2023-05-03
• Study First Submitted QC: 2023-05-19
• Study First Posted: 2023-05-30
• Study Start: 2023-07-24
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-19
• Last Update Posted: 2025-06-25
• Primary Completion: 2026-06-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 66

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Eflornithine Dose Level 2 + Temozolomide	Eflornithine (Dose Level 2)	-
Eflornithine Dose Level 1 + Temozolomide	Eflornithine (Dose Level 1)	-
Eflornithine Dose Level -1 + Temozolomide	Eflornithine (Dose Level -1)	-
Eflornithine Dose Level -1 + Temozolomide	Temozolomide	-
Eflornithine Dose Level 2 + Temozolomide	Temozolomide	-
Eflornithine Dose Level 1 + Temozolomide	Temozolomide	-

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Abnormalities in Clinical Laboratory Tests	From enrollment to the follow-up visit 4 weeks after end of treatment	Lab abnormalities by CTCAE v5.0 Grade
Assessment of Dose Limiting Toxicities	8 weeks	Protocol Defined Dose Limiting Toxicities
Incidence of TEAEs All Grades	From enrollment to the follow-up visit 4 weeks after end of treatment	All Grades
Incidence of TEAEs Grade 3+	From enrollment to the follow-up visit 4 weeks after end of treatment	Grade 3+
Incidence of TEAEs Serious	From enrollment to the follow-up visit 4 weeks after end of treatment	Serious
Incidence of TEAEs Leading to Discontinuation	From enrollment to the end of treatment	Leading to Discontinuation
Vital Signs (Heart and Respiratory Rate)	From enrollment to the follow-up visit 4 weeks after end of treatment	Change from Baseline in Heart Rate and Respiratory Rate
Vital Signs (Blood Pressure)	From enrollment to the follow-up visit 4 weeks after end of treatment	Change from Baseline in Systolic Blood Pressure and Diastolic Blood Pressure

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival	From enrollment to the follow-up visit 4 weeks after end of treatment	Per RANO Criteria as assessed by MRI
Overall Response Rate	From enrollment to the follow-up visit 4 weeks after end of treatment	Per RANO Criteria as assessed by MRI
Pharmacokinetics Cmax	Baseline to Steady State (2 weeks)	observed maximum concentration
Pharmacokinetics Cmin	Baseline to Steady State (2 weeks)	observed minimum concentration
Pharmacokinetics Tmax	Baseline to Steady State (2 weeks)	time of observed maximum concentration
Pharmacokinetics AUCt	Baseline to Steady State (2 weeks)	area under the concentration-time curve
Pharmacokinetics lambdaz	Baseline to Steady State (2 weeks)	elimination rate constant
Pharmacokinetics t 1/2	Baseline to Steady State (2 weeks)	elimination half life
QTcF-Concentration Relationship	Baseline to Steady State (2 weeks)	Assessment of change in QTcF relative to plasma concentration of eflornithine
Assessment of QTcF	Baseline to Steady State (2 weeks)	Change from baseline in QTcF
Overall Survival	From enrollment to up to 2 years after last dose	Until death or initiation of new anticancer therapy

Trial Locations

Locations (8)

Brown University Health/Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

Columbia University Medical Center - Herbert Irving Pavilion; 🇺🇸 New York, New York, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

The Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

UT MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

University of Utah, Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States