Clinical trial NCT05879367: Evaluation of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma
Official title: An Open-label, Phase 1b Study to Evaluate the Safety and Tolerability of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Glioblastoma, IDH-wildtype
Glioblastoma
Glioblastoma Multiforme
Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype
GBM
Lead sponsor: Orbus Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-05-30
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Assessment of Dose Limiting Toxicities
timeFrame: 8 weeks
measure: Incidence of TEAEs All Grades
timeFrame: 52 weeks
measure: Incidence of TEAEs Grade 3+
timeFrame: 52 weeks
measure: Incidence of TEAEs Serious
timeFrame: 52 weeks
measure: Incidence of TEAEs Leading to Discontinuation
timeFrame: 48 weeks
measure: Vital Signs (Heart and Respiratory Rate)
timeFrame: 52 weeks
measure: Vital Signs (Blood Pressure)
timeFrame: 52 weeks
measure: Incidence of Treatment-Emergent Abnormalities in Clinical Laboratory Tests
timeFrame: 52 weeks
Secondary outcomes:
measure: Progression Free Survival
timeFrame: 52 weeks
measure: Overall Response Rate
timeFrame: 52 weeks
measure: Pharmacokinetics Cmax
timeFrame: Baseline to Steady State (2 weeks)
measure: Pharmacokinetics Cmin
timeFrame: Baseline to Steady State (2 weeks)
measure: Pharmacokinetics Tmax
timeFrame: Baseline to Steady State (2 weeks)
measure: Pharmacokinetics AUCt
timeFrame: Baseline to Steady State (2 weeks)
measure: Pharmacokinetics lambdaz
timeFrame: Baseline to Steady State (2 weeks)
measure: Pharmacokinetics t 1/2
timeFrame: Baseline to Steady State (2 weeks)
measure: QTcF-Concentration Relationship
timeFrame: Baseline to Steady State (2 weeks)
measure: Assessment of QTcF
timeFrame: Baseline to Steady State (2 weeks)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: New York
country: United States
facility: Columbia University Medical Center - Herbert Irving Pavilion
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
city: Providence
country: United States
facility: Lifespan Cancer Institute/Rhode Island Hospital
state: Rhode Island
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah, Huntsman Cancer Institute
state: Utah
Study officials:
affiliation: Huntsman Cancer Institute/ University of Utah
name: Howard Colman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: