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Evaluation of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma or Astrocytoma

NCT05879367 · Orbus Therapeutics, Inc.
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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
About this study
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).
Eligibility criteria
Inclusion Criteria: * 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. Exclusion Criteria: * 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.
Study design
Enrollment target: 66 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2023-07-24
Estimated completion: 2026-06-30
Last updated: 2025-06-25
Interventions
Drug: Eflornithine (Dose Level 1)Drug: Eflornithine (Dose Level 2)Drug: Eflornithine (Dose Level -1)Drug: Temozolomide
Primary outcomes
  • Assessment of Dose Limiting Toxicities (8 weeks)
  • Incidence of TEAEs All Grades (From enrollment to the follow-up visit 4 weeks after end of treatment)
  • Incidence of TEAEs Grade 3+ (From enrollment to the follow-up visit 4 weeks after end of treatment)
Sponsor
Orbus Therapeutics, Inc. · industry
Contacts & investigators
ContactMonika Varga · contact · monika.varga@orbustherapeutics.com · 6506569424
InvestigatorHoward Colman, MD, PhD · principal_investigator, Huntsman Cancer Institute/ University of Utah
All locations (8)
University of Alabama at BirminghamWithdrawn
Birmingham, Alabama, United States
Henry Ford HospitalRecruiting
Detroit, Michigan, United States
Columbia University Medical Center - Herbert Irving PavilionRecruiting
New York, New York, United States
Duke UniversityRecruiting
Durham, North Carolina, United States
The Cleveland ClinicRecruiting
Cleveland, Ohio, United States
Brown University Health/Rhode Island HospitalRecruiting
Providence, Rhode Island, United States
UT MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
University of Utah, Huntsman Cancer InstituteRecruiting
Salt Lake City, Utah, United States
Evaluation of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma or Astrocytoma · TrialPath