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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05879367
Other study ID # OT-21-101
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
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
Health authority
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.

Study Design


Related Conditions & MeSH terms


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)
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