Glioblastoma, IDH-wildtypePhase 1NCT05879367
Evaluation of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma or Astrocytoma
A Phase 1 study testing Eflornithine (Dose Level 1), Eflornithine (Dose Level 2) and Eflornithine (Dose Level -1) in people with Glioblastoma, IDH-wildtype and Glioblastoma, run by Orbus Therapeutics, Inc. at 8 sites in United States.
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 or astrocytoma is newly diagnosed, and to evaluate safety and tolerability of this combination at that dose. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, IDH-wildtype, Glioblastoma, Glioblastoma Multiforme
- What is being tested?
- Eflornithine (Dose Level 1), Eflornithine (Dose Level 2) and Eflornithine (Dose Level -1)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 8 sitesUnited States
- Study dates
- 24 Jul 2023to 30 Jun 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of World Health Organization (WHO) G4 classified GBM, IDH-wildtype (patients with GBM) or G3 astrocytoma (IDH1 or 2 mutant; CDKN2A/B intact) per WHO 2021 tumor classification.
- Completed external beam radiation therapy per standard of care.
- Patients with GBM: Must have received at least 80% of planned daily doses of TMZ during chemoradiation. Patients with astrocytoma: Must have tolerated adjuvant TMZ treatment through at least 2 and not more than 4 cycles.
- 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.
Who cannot join
- Recent history of recurrent or metastatic cancer that could confound response assessments
- Prior systemic chemotherapy other than temozolomide during external beam radiation therapy (for patients with GBM) or adjuvant temozolomide through up to 4 pre-study cycles (for patients with astrocytoma).
- 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.
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
United States8 sites, 7 recruiting
- Withdrawn
University of Alabama at Birmingham
Birmingham, Alabama, 35294
- Recruiting
The Cleveland Clinic
Cleveland, Ohio, 44195
David Peereboom, MD, 216-445-6068, peerebd@ccf.org
Rachel Hufsey, RN, hufseyr@ccf.org
- Recruiting
Henry Ford Hospital
Detroit, Michigan, 48202
Meghan Gauronskas, 313-725-7871, mgauron1@hfhs.org
Angela Dunn, 313-725-7870, adunn6@hfhs.org
- Recruiting
Duke University
Durham, North Carolina, 27710
Erin Severance, 919-668-6230, erin.k.bell@duke.edu
Annick Desjardins, MD, FRCPC
- Recruiting
UT MD Anderson Cancer Center
Houston, Texas, 77030
Carlos Kamiya Matsuoka, MD, 713-408-3538, CKamiya@mdanderson.org
Evguenia Gachimova, RN, 832-266-3519, Egachimova@mdanderson.org
- Recruiting
Columbia University Medical Center - Herbert Irving Pavilion
New York, New York, 10032
Maria Diaz, MD, 212-342-0571, md4157@cumc.columbia.edu
Nurse Navigators, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu
- Recruiting
Brown University Health/Rhode Island Hospital
Providence, Rhode Island, 02903
Nuno Rodrigues, RN, 401.444.3059, Nuno.Rodrigues@brownhealth.org
Gada Alam, 401-444-6217, GAlam@brownhealth.org
- Recruiting
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Rachel Kingsford, 801-585-0115, rachel.kingsford@hci.utah.edu
Yuri Kida, 801-646-4397, yuri.kida@hci.utah.edu
About this study
Official title: An Open-label, Phase 1b Study to Evaluate the Safety and Tolerability of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma or Astrocytoma
The purpose of this study is to establish the recommended phase 2 dose of eflornithine in combination with temozolomide in patients whose glioblastoma or astrocytoma is newly diagnosed, and to evaluate safety and tolerability of this combination at that dose.
Read the 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 approximately 104 weeks in total per patient.
Screening Period - A maximum screening duration of 4 weeks.
Treatment Period - Up to approximately 104 weeks.
Follow-Up Visit - 4 weeks from last treatment.
Long-term Survival Follow-Up - up to 2 years 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).
- Conditions
- Glioblastoma, IDH-wildtype, Glioblastoma, Glioblastoma Multiforme, Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype, GBM, Astrocytoma
- Being tested
- Eflornithine (Dose Level 1), Eflornithine (Dose Level 2), Eflornithine (Dose Level -1), Temozolomide
- Medical subject headings
- Glioblastoma, Astrocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eflornithine (Dose Level 1)Drug
Also called DFMO
Eflornithine 2.3 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule
Eflornithine (Dose Level 2)Drug
Also called DFMO
Eflornithine 2.8 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule
Eflornithine (Dose Level -1)Drug
Also called DFMO
Eflornithine 1.75 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule
TemozolomideDrug
Also called Temodar, TMZ
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
| Study group | Role | What they receive |
|---|---|---|
| Eflornithine Dose Level 1 + Temozolomide | Experimental | Not described Receives: Drug: Eflornithine (Dose Level 1); Drug: Temozolomide |
| Eflornithine Dose Level 2 + Temozolomide | Experimental | Not described Receives: Drug: Eflornithine (Dose Level 2); Drug: Temozolomide |
| Eflornithine Dose Level -1 + Temozolomide | Experimental | Not described Receives: Drug: Eflornithine (Dose Level -1); Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of Dose Limiting Toxicities
Protocol Defined Dose Limiting Toxicities
Measured: 8 weeks
Incidence of TEAEs All Grades
All Grades
Measured: From enrollment to the follow-up visit 4 weeks after end of treatment
Incidence of TEAEs Grade 3+
Grade 3+
Measured: From enrollment to the follow-up visit 4 weeks after end of treatment
Incidence of TEAEs Serious
Serious
Measured: From enrollment to the follow-up visit 4 weeks after end of treatment
Incidence of TEAEs Leading to Discontinuation
Leading to Discontinuation
Measured: From enrollment to the end of treatment
Vital Signs (Heart and Respiratory Rate)
Change from Baseline in Heart Rate and Respiratory Rate
Measured: From enrollment to the follow-up visit 4 weeks after end of treatment
Vital Signs (Blood Pressure)
Change from Baseline in Systolic Blood Pressure and Diastolic Blood Pressure
Measured: From enrollment to the follow-up visit 4 weeks after end of treatment
Incidence of Treatment-Emergent Abnormalities in Clinical Laboratory Tests
Lab abnormalities by CTCAE v5.0 Grade
Measured: From enrollment to the follow-up visit 4 weeks after end of treatment
Secondary outcomes (11)
Overall Survival
Until death or initiation of new anticancer therapy
Measured: From enrollment to up to 2 years after last dose
Progression Free Survival
Per RANO Criteria as assessed by MRI
Measured: From enrollment to the follow-up visit 4 weeks after end of treatment
Overall Response Rate
Per RANO Criteria as assessed by MRI
Measured: From enrollment to the follow-up visit 4 weeks after end of treatment
Pharmacokinetics Cmax
observed maximum concentration
Measured: Baseline to Steady State (2 weeks)
Pharmacokinetics Cmin
observed minimum concentration
Measured: Baseline to Steady State (2 weeks)
Pharmacokinetics Tmax
time of observed maximum concentration
Measured: Baseline to Steady State (2 weeks)
Pharmacokinetics AUCt
area under the concentration-time curve
Measured: Baseline to Steady State (2 weeks)
Pharmacokinetics lambdaz
elimination rate constant
Measured: Baseline to Steady State (2 weeks)
Pharmacokinetics t 1/2
elimination half life
Measured: Baseline to Steady State (2 weeks)
QTcF-Concentration Relationship
Assessment of change in QTcF relative to plasma concentration of eflornithine
Measured: Baseline to Steady State (2 weeks)
Assessment of QTcF
Change from baseline in QTcF
Measured: Baseline to Steady State (2 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2023
- Study start24 Jul 2023
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma, IDH-wildtypeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Orbus Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Howard Colman, MD, PhD, Principal investigator, Huntsman Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05879367
- Sponsor's protocol ID
- OT-21-101
- Status last verified
- Jun 2025
- First submitted
- 3 May 2023
- Last updated
- 25 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Phase 1b Study to Evaluate the Safety and Tolerability of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma or Astrocytoma
- ClinicalTrials.gov ID
- NCT05879367
- Acronym / sponsor ID
- OT-21-101
- Conditions
- Glioblastoma, IDH-wildtype, Glioblastoma, Glioblastoma Multiforme, Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype, GBM, Astrocytoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 66 participants (estimated)
- Lead sponsor
- Orbus Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 24 Jul 2023 (actual)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 30 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to establish the recommended phase 2 dose of eflornithine in combination with temozolomide in patients whose glioblastoma or astrocytoma 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 approximately 104 weeks in total per patient.
Screening Period - A maximum screening duration of 4 weeks.
Treatment Period - Up to approximately 104 weeks.
Follow-Up Visit - 4 weeks from last treatment.
Long-term Survival Follow-Up - up to 2 years 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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Eflornithine Dose Level 1 + Temozolomide | Experimental | Drug: Eflornithine (Dose Level 1), Drug: Temozolomide |
| Eflornithine Dose Level 2 + Temozolomide | Experimental | Drug: Eflornithine (Dose Level 2), Drug: Temozolomide |
| Eflornithine Dose Level -1 + Temozolomide | Experimental | Drug: Eflornithine (Dose Level -1), Drug: Temozolomide |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosis of World Health Organization (WHO) G4 classified GBM, IDH-wildtype (patients with GBM) or G3 astrocytoma (IDH1 or 2 mutant; CDKN2A/B intact) per WHO 2021 tumor classification.
- Completed external beam radiation therapy per standard of care.
- Patients with GBM: Must have received at least 80% of planned daily doses of TMZ during chemoradiation. Patients with astrocytoma: Must have tolerated adjuvant TMZ treatment through at least 2 and not more than 4 cycles.
- 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.
Key exclusion criteria (8 listed)
- Recent history of recurrent or metastatic cancer that could confound response assessments
- Prior systemic chemotherapy other than temozolomide during external beam radiation therapy (for patients with GBM) or adjuvant temozolomide through up to 4 pre-study cycles (for patients with astrocytoma).
- Prior Optune treatment.
- Active infection or serious intercurrent medical illness.
- Poorly controlled seizures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eflornithine (Dose Level 1)Also: DFMOEflornithine 2.3 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule | Drug | Eflornithine Dose Level 1 + Temozolomide |
| Eflornithine (Dose Level 2)Also: DFMOEflornithine 2.8 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule | Drug | Eflornithine Dose Level 2 + Temozolomide |
| Eflornithine (Dose Level -1)Also: DFMOEflornithine 1.75 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule | Drug | Eflornithine Dose Level -1 + Temozolomide |
| TemozolomideAlso: Temodar, TMZTemozolomide 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 | Drug | Eflornithine Dose Level -1 + Temozolomide, Eflornithine Dose Level 1 + Temozolomide, Eflornithine Dose Level 2 + Temozolomide |
Primary outcome
Assessment of Dose Limiting Toxicities
Time frame: 8 weeks
Protocol Defined Dose Limiting Toxicities
Incidence of TEAEs All Grades
Time frame: From enrollment to the follow-up visit 4 weeks after end of treatment
All Grades
Incidence of TEAEs Grade 3+
Time frame: From enrollment to the follow-up visit 4 weeks after end of treatment
Grade 3+
Incidence of TEAEs Serious
Time frame: From enrollment to the follow-up visit 4 weeks after end of treatment
Serious
Incidence of TEAEs Leading to Discontinuation
Time frame: From enrollment to the end of treatment
Leading to Discontinuation
Vital Signs (Heart and Respiratory Rate)
Time frame: From enrollment to the follow-up visit 4 weeks after end of treatment
Change from Baseline in Heart Rate and Respiratory Rate
Vital Signs (Blood Pressure)
Time frame: From enrollment to the follow-up visit 4 weeks after end of treatment
Change from Baseline in Systolic Blood Pressure and Diastolic Blood Pressure
Incidence of Treatment-Emergent Abnormalities in Clinical Laboratory Tests
Time frame: From enrollment to the follow-up visit 4 weeks after end of treatment
Lab abnormalities by CTCAE v5.0 Grade
11 secondary outcomes
Overall Survival
Time frame: From enrollment to up to 2 years after last dose
Progression Free Survival
Time frame: From enrollment to the follow-up visit 4 weeks after end of treatment
Overall Response Rate
Time frame: From enrollment to the follow-up visit 4 weeks after end of treatment
Pharmacokinetics Cmax
Time frame: Baseline to Steady State (2 weeks)
Pharmacokinetics Cmin
Time frame: Baseline to Steady State (2 weeks)
Pharmacokinetics Tmax
Time frame: Baseline to Steady State (2 weeks)
Pharmacokinetics AUCt
Time frame: Baseline to Steady State (2 weeks)
Pharmacokinetics lambdaz
Time frame: Baseline to Steady State (2 weeks)
Pharmacokinetics t 1/2
Time frame: Baseline to Steady State (2 weeks)
QTcF-Concentration Relationship
Time frame: Baseline to Steady State (2 weeks)
Assessment of QTcF
Time frame: Baseline to Steady State (2 weeks)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Howard Colman, MD, PhD principal investigator
Huntsman Cancer Institute
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Eflornithine (Dose Level 1), Eflornithine (Dose Level 2) and Eflornithine (Dose Level -1) in people with Glioblastoma, IDH-wildtype and Glioblastoma, run by Orbus Therapeutics, Inc. at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Monika Varga (6506569424, monika.varga@orbustherapeutics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of Dose Limiting Toxicities (time frame: 8 weeks). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2025.