Evaluation of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma
- Conditions
- Glioblastoma, IDH-wildtypeGlioblastoma MultiformeGlioblastomaGlioblastoma IDH (Isocitrate Dehydrogenase) WildtypeGBM
- Interventions
- 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 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 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 & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 66
- 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.
- 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.
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 TEAEs Grade 3+ 52 weeks Grade 3+
Assessment of Dose Limiting Toxicities 8 weeks Protocol Defined Dose Limiting Toxicities
Incidence of TEAEs Serious 52 weeks Serious
Incidence of TEAEs Leading to Discontinuation 48 weeks Leading to Discontinuation
Incidence of Treatment-Emergent Abnormalities in Clinical Laboratory Tests 52 weeks Lab abnormalities by CTCAE v5.0 Grade
Vital Signs (Blood Pressure) 52 weeks Change from Baseline in Systolic Blood Pressure and Diastolic Blood Pressure
Incidence of TEAEs All Grades 52 weeks All Grades
Vital Signs (Heart and Respiratory Rate) 52 weeks Change from Baseline in Heart Rate and Respiratory Rate
- Secondary Outcome Measures
Name Time Method Overall Response Rate 52 weeks Per RANO Criteria as assessed by MRI
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
Pharmacokinetics Cmax Baseline to Steady State (2 weeks) observed maximum concentration
Progression Free Survival 52 weeks Per RANO Criteria as assessed by MRI
Pharmacokinetics Cmin Baseline to Steady State (2 weeks) observed minimum concentration
Pharmacokinetics Tmax Baseline to Steady State (2 weeks) time of observed maximum concentration
Trial Locations
- Locations (8)
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
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
Lifespan Cancer Institute/Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States