Evaluation of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 60 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
Arms and Interventions
| 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:
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:
|
| Experimental: Eflornithine Dose Level 2 + Temozolomide
|
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:
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:
|
| Experimental: Eflornithine Dose Level -1 + Temozolomide
|
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:
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:
|
Outcome Measures
Primary Outcome Measures
- Assessment of Dose Limiting Toxicities [8 weeks]
- Incidence of TEAEs [52 weeks]
All Grades
- Incidence of TEAEs [52 weeks]
Grade 3+
- Incidence of TEAEs [52 weeks]
Serious
- Incidence of TEAEs [48 weeks]
Leading to Discontinuation
- Vital Signs (Heart and Respiratory Rate) [52 weeks]
Change from Baseline in Heart Rate and Respiratory Rate
- Vital Signs (Blood Pressure) [52 weeks]
Change from Baseline in Systolic Blood Pressure and Diastolic Blood Pressure
- Incidence of Treatment-Emergent Abnormalities in Clinical Laboratory Tests [52 weeks]
Lab abnormalities by CTCAE v5.0 Grade
Secondary Outcome Measures
- Progression Free Survival [52 weeks]
Per RANO Criteria as assessed by MRI
- Overall Response Rate [52 weeks]
Per RANO Criteria as assessed by MRI
- Pharmacokinetics Cmax [Baseline to Steady State (2 weeks)]
observed maximum concentration
- Pharmacokinetics Cmin [Baseline to Steady State (2 weeks)]
observed minimum concentration
- Pharmacokinetics Tmax [Baseline to Steady State (2 weeks)]
time of observed maximum concentration
- 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
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
Sponsors and Collaborators
- Orbus Therapeutics, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- OT-21-101