An Open-label, Phase 1b Study to Evaluate the Safety and Tolerability of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma or Astrocytoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 66
- 试验地点
- 8
- 主要终点
- Assessment of Dose Limiting Toxicities
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Eflornithine Dose Level 1 + Temozolomide
干预措施: Eflornithine (Dose Level 1) (Drug)
Eflornithine Dose Level 1 + Temozolomide
干预措施: Temozolomide (Drug)
Eflornithine Dose Level 2 + Temozolomide
干预措施: Eflornithine (Dose Level 2) (Drug)
Eflornithine Dose Level 2 + Temozolomide
干预措施: Temozolomide (Drug)
Eflornithine Dose Level -1 + Temozolomide
干预措施: Eflornithine (Dose Level -1) (Drug)
Eflornithine Dose Level -1 + Temozolomide
干预措施: Temozolomide (Drug)
结局指标
主要结局
Assessment of Dose Limiting Toxicities
时间窗: 8 weeks
Protocol Defined Dose Limiting Toxicities
Incidence of TEAEs All Grades
时间窗: From enrollment to the follow-up visit 4 weeks after end of treatment
All Grades
Incidence of TEAEs Grade 3+
时间窗: From enrollment to the follow-up visit 4 weeks after end of treatment
Grade 3+
Incidence of TEAEs Serious
时间窗: From enrollment to the follow-up visit 4 weeks after end of treatment
Serious
Incidence of TEAEs Leading to Discontinuation
时间窗: From enrollment to the end of treatment
Leading to Discontinuation
Vital Signs (Heart and Respiratory Rate)
时间窗: 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)
时间窗: 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
时间窗: From enrollment to the follow-up visit 4 weeks after end of treatment
Lab abnormalities by CTCAE v5.0 Grade
次要结局
- Overall Survival(From enrollment to up to 2 years after last dose)
- Progression Free Survival(From enrollment to the follow-up visit 4 weeks after end of treatment)
- Overall Response Rate(From enrollment to the follow-up visit 4 weeks after end of treatment)
- Pharmacokinetics Cmax(Baseline to Steady State (2 weeks))
- Pharmacokinetics Cmin(Baseline to Steady State (2 weeks))
- Pharmacokinetics Tmax(Baseline to Steady State (2 weeks))
- Pharmacokinetics AUCt(Baseline to Steady State (2 weeks))
- Pharmacokinetics lambdaz(Baseline to Steady State (2 weeks))
- Pharmacokinetics t 1/2(Baseline to Steady State (2 weeks))
- QTcF-Concentration Relationship(Baseline to Steady State (2 weeks))
- Assessment of QTcF(Baseline to Steady State (2 weeks))