Evaluation of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma

Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05879367
• Other study ID #: OT-21-101
• Status: Recruiting
• Phase: Phase 1
• Start date: July 24, 2023
• Est. completion date: December 15, 2024

Study information

• Verified date: April 2024
• Source: Orbus Therapeutics, Inc.
• Contact: Monika Varga
• Phone: 6506569424
• Email: monika.varga[@]orbustherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: December 15, 2024
• Est. primary completion date: December 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• GBM
• Glioblastoma
• Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype
• Glioblastoma Multiforme
• Glioblastoma, IDH-wildtype

Intervention

Drug:
• Eflornithine (Dose Level 1)
Eflornithine 2.3 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule
• Eflornithine (Dose Level 2)
Eflornithine 2.8 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule
• Eflornithine (Dose Level -1)
Eflornithine 1.75 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule
• Temozolomide
Temozolomide 150 mg/m2 (with option to escalate per USPI maintenance phase instructions) administered orally once daily on a 5 days on, 23 days off schedule

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	The Cleveland Clinic	Cleveland	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	UT MD Anderson Cancer Center	Houston	Texas
United States	Columbia University Medical Center - Herbert Irving Pavilion	New York	New York
United States	Lifespan Cancer Institute/Rhode Island Hospital	Providence	Rhode Island
United States	University of Utah, Huntsman Cancer Institute	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Orbus Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of Dose Limiting Toxicities	Protocol Defined Dose Limiting Toxicities	8 weeks
Primary	Incidence of TEAEs All Grades	All Grades	52 weeks
Primary	Incidence of TEAEs Grade 3+	Grade 3+	52 weeks
Primary	Incidence of TEAEs Serious	Serious	52 weeks
Primary	Incidence of TEAEs Leading to Discontinuation	Leading to Discontinuation	48 weeks
Primary	Vital Signs (Heart and Respiratory Rate)	Change from Baseline in Heart Rate and Respiratory Rate	52 weeks
Primary	Vital Signs (Blood Pressure)	Change from Baseline in Systolic Blood Pressure and Diastolic Blood Pressure	52 weeks
Primary	Incidence of Treatment-Emergent Abnormalities in Clinical Laboratory Tests	Lab abnormalities by CTCAE v5.0 Grade	52 weeks
Secondary	Progression Free Survival	Per RANO Criteria as assessed by MRI	52 weeks
Secondary	Overall Response Rate	Per RANO Criteria as assessed by MRI	52 weeks
Secondary	Pharmacokinetics Cmax	observed maximum concentration	Baseline to Steady State (2 weeks)
Secondary	Pharmacokinetics Cmin	observed minimum concentration	Baseline to Steady State (2 weeks)
Secondary	Pharmacokinetics Tmax	time of observed maximum concentration	Baseline to Steady State (2 weeks)
Secondary	Pharmacokinetics AUCt	area under the concentration-time curve	Baseline to Steady State (2 weeks)
Secondary	Pharmacokinetics lambdaz	elimination rate constant	Baseline to Steady State (2 weeks)
Secondary	Pharmacokinetics t 1/2	elimination half life	Baseline to Steady State (2 weeks)
Secondary	QTcF-Concentration Relationship	Assessment of change in QTcF relative to plasma concentration of eflornithine	Baseline to Steady State (2 weeks)
Secondary	Assessment of QTcF	Change from baseline in QTcF	Baseline to Steady State (2 weeks)