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

Официальное название

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

Обзор

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.

Подробное описание

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).

Вмешательства

• Препарат Eflornithine (Dose Level 1)
  Eflornithine 2.3 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule
• Препарат Eflornithine (Dose Level 2)
  Eflornithine 2.8 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule
• Препарат Eflornithine (Dose Level -1)
  Eflornithine 1.75 g/m2 administered orally every 8 hours on a 2 weeks on, 2 weeks off schedule
• Препарат 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

Первичные конечные точки

• Assessment of Dose Limiting Toxicities [Срок оценки: 8 weeks]
• Incidence of TEAEs All Grades [Срок оценки: From enrollment to the follow-up visit 4 weeks after end of treatment]
• Incidence of TEAEs Grade 3+ [Срок оценки: From enrollment to the follow-up visit 4 weeks after end of treatment]
• Incidence of TEAEs Serious [Срок оценки: From enrollment to the follow-up visit 4 weeks after end of treatment]
• Incidence of TEAEs Leading to Discontinuation [Срок оценки: From enrollment to the end of treatment]
• Vital Signs (Heart and Respiratory Rate) [Срок оценки: From enrollment to the follow-up visit 4 weeks after end of treatment]
• Vital Signs (Blood Pressure) [Срок оценки: From enrollment to the follow-up visit 4 weeks after end of treatment]
• Incidence of Treatment-Emergent Abnormalities in Clinical Laboratory Tests [Срок оценки: From enrollment to the follow-up visit 4 weeks after end of treatment]

Вторичные конечные точки (11)

• Overall Survival [Срок оценки: From enrollment to up to 2 years after last dose]
• Progression Free Survival [Срок оценки: From enrollment to the follow-up visit 4 weeks after end of treatment]
• Overall Response Rate [Срок оценки: From enrollment to the follow-up visit 4 weeks after end of treatment]
• Pharmacokinetics Cmax [Срок оценки: Baseline to Steady State (2 weeks)]
• Pharmacokinetics Cmin [Срок оценки: Baseline to Steady State (2 weeks)]
• Pharmacokinetics Tmax [Срок оценки: Baseline to Steady State (2 weeks)]
• Pharmacokinetics AUCt [Срок оценки: Baseline to Steady State (2 weeks)]
• Pharmacokinetics lambdaz [Срок оценки: Baseline to Steady State (2 weeks)]
• Pharmacokinetics t 1/2 [Срок оценки: Baseline to Steady State (2 weeks)]
• QTcF-Concentration Relationship [Срок оценки: Baseline to Steady State (2 weeks)]
• Assessment of QTcF [Срок оценки: Baseline to Steady State (2 weeks)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 8 центров

• University of Alabama at Birmingham — Birmingham
• Henry Ford Hospital — Detroit
• Columbia University Medical Center - Herbert Irving Pavilion — New York
• Duke University — Durham
• The Cleveland Clinic — Cleveland
• Brown University Health/Rhode Island Hospital — Providence
• UT MD Anderson Cancer Center — Houston
• University of Utah, Huntsman Cancer Institute — Salt Lake City

Идентификаторы

NCT: NCT05879367 · OT-21-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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