Evaluation of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma

April 16, 2024 updated by: Orbus Therapeutics, Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Estimated)

66

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Recruiting
        • University of Alabama at Birmingham
        • Principal Investigator:
          • Louis B Nabors, MD
        • Contact:
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Hospital
        • Principal Investigator:
          • Tobias Walbert, MD, PhD, MPH
        • Contact:
        • Contact:
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Medical Center - Herbert Irving Pavilion
        • Contact:
        • Contact:
        • Principal Investigator:
          • Maria Diaz, MD
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University
        • Principal Investigator:
          • Annick Desjardins, MD, FRCPC
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • The Cleveland Clinic
        • Principal Investigator:
          • David Peereboom, MD
        • Contact:
        • Contact:
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Lifespan Cancer Institute/Rhode Island Hospital
        • Principal Investigator:
          • Eric Wong, MD
        • Contact:
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • UT MD Anderson Cancer Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Carlos Kamiya Matsuoka, MD
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • University of Utah, Huntsman Cancer Institute
        • Principal Investigator:
          • Howard Colman, MD, PhD
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Eflornithine Dose Level 1 + Temozolomide
Drug: Eflornithine (Dose Level 1)
Eflornithine 2.3 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule
Other Names:
  • DFMO
Drug: 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
Other Names:
  • Temodar
  • TMZ
Experimental: Eflornithine Dose Level 2 + Temozolomide
Drug: 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
Other Names:
  • Temodar
  • TMZ
Drug: Eflornithine (Dose Level 2)
Eflornithine 2.8 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule
Other Names:
  • DFMO
Experimental: Eflornithine Dose Level -1 + Temozolomide
Drug: 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
Other Names:
  • Temodar
  • TMZ
Drug: Eflornithine (Dose Level -1)
Eflornithine 1.75 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule
Other Names:
  • DFMO

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Vital Signs (Heart and Respiratory Rate)
Time Frame: 52 weeks
Change from Baseline in Heart Rate and Respiratory Rate
52 weeks
Vital Signs (Blood Pressure)
Time Frame: 52 weeks
Change from Baseline in Systolic Blood Pressure and Diastolic Blood Pressure
52 weeks
Incidence of Treatment-Emergent Abnormalities in Clinical Laboratory Tests
Time Frame: 52 weeks
Lab abnormalities by CTCAE v5.0 Grade
52 weeks
Assessment of Dose Limiting Toxicities
Time Frame: 8 weeks
Protocol Defined Dose Limiting Toxicities
8 weeks
Incidence of TEAEs All Grades
Time Frame: 52 weeks
All Grades
52 weeks
Incidence of TEAEs Grade 3+
Time Frame: 52 weeks
Grade 3+
52 weeks
Incidence of TEAEs Serious
Time Frame: 52 weeks
Serious
52 weeks
Incidence of TEAEs Leading to Discontinuation
Time Frame: 48 weeks
Leading to Discontinuation
48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: 52 weeks
Per RANO Criteria as assessed by MRI
52 weeks
Overall Response Rate
Time Frame: 52 weeks
Per RANO Criteria as assessed by MRI
52 weeks
Pharmacokinetics Cmax
Time Frame: Baseline to Steady State (2 weeks)
observed maximum concentration
Baseline to Steady State (2 weeks)
Pharmacokinetics Cmin
Time Frame: Baseline to Steady State (2 weeks)
observed minimum concentration
Baseline to Steady State (2 weeks)
Pharmacokinetics Tmax
Time Frame: Baseline to Steady State (2 weeks)
time of observed maximum concentration
Baseline to Steady State (2 weeks)
Pharmacokinetics AUCt
Time Frame: Baseline to Steady State (2 weeks)
area under the concentration-time curve
Baseline to Steady State (2 weeks)
Pharmacokinetics lambdaz
Time Frame: Baseline to Steady State (2 weeks)
elimination rate constant
Baseline to Steady State (2 weeks)
Pharmacokinetics t 1/2
Time Frame: Baseline to Steady State (2 weeks)
elimination half life
Baseline to Steady State (2 weeks)
QTcF-Concentration Relationship
Time Frame: Baseline to Steady State (2 weeks)
Assessment of change in QTcF relative to plasma concentration of eflornithine
Baseline to Steady State (2 weeks)
Assessment of QTcF
Time Frame: Baseline to Steady State (2 weeks)
Change from baseline in QTcF
Baseline to Steady State (2 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Orbus Therapeutics, Inc.

Investigators

  • Principal Investigator: Howard Colman, MD, PhD, Huntsman Cancer Institute/ University of Utah

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 24, 2023

Primary Completion (Estimated)

December 15, 2024

Study Completion (Estimated)

December 15, 2024

Study Registration Dates

First Submitted

May 3, 2023

First Submitted That Met QC Criteria

May 19, 2023

First Posted (Actual)

May 30, 2023

Study Record Updates

Last Update Posted (Actual)

April 18, 2024

Last Update Submitted That Met QC Criteria

April 16, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OT-21-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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