A Phase 1B/2A Study of the Safety, Tolerability and Initial Efficacy of Oral AMXT 1501 Dicaprate and Intravenous Difluoromethylornithine (DFMO) in Patients With Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 15
- 试验地点
- 7
- 主要终点
- Determine safety and tolerability of AMXT1501 in combination with IV DFMO
研究概览
简要总结
A Phase 1B/2A study will be conducted to establish safety and dose level of AMXT 1501 dicaprate in combination with IV DFMO, in cancer patients.
详细描述
The objective of this study is to determine the safety and tolerability of oral AMXT 1501 dicaprate (AMXT1501) in combination with IV DFMO in patients with advanced solid tumors, or DIPG/DMG. Secondary objectives include characterization of plasma pharmacokinetics (PK), pharmacodynamic (PD), and other biomarker efficacy assessments of the impact of AMXT 1501 in combination with IV DFMO on polyamine uptake by circulating lymphocytes (blood cells). To these aims, the study will evaluate the safety, PK, PD, and other biomarker efficacy profiles of orally-administered AMXT 1501 and IV DFMO. Approximately, 56 patients will be enrolled to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMXT 1501 and IV DFMO in combination. The MTD is defined as the highest dose level below at which dose escalation is stopped.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Escalation
Dose escalation of DFMO with AMXT1501 fixed dose will follow a 3 + 3 dose escalation design.
The AMXT 1501 starting dose administered in the first cohort will be 1200mg total daily dose (200 mg capsules; 3 capsules in morning; 3 capsules in evening) along with IV DFMO administered in continuous infusion at 2mL/hr over a 28 days per cycle. The patient can be treated for additional 28 day treatment cycles as deemed appropriate by their study investigator. Dose escalation of DFMO alone will increase per cohort.
干预措施: AMXT1501 (Drug)
Escalation
Dose escalation of DFMO with AMXT1501 fixed dose will follow a 3 + 3 dose escalation design.
The AMXT 1501 starting dose administered in the first cohort will be 1200mg total daily dose (200 mg capsules; 3 capsules in morning; 3 capsules in evening) along with IV DFMO administered in continuous infusion at 2mL/hr over a 28 days per cycle. The patient can be treated for additional 28 day treatment cycles as deemed appropriate by their study investigator. Dose escalation of DFMO alone will increase per cohort.
干预措施: DFMO (Drug)
Expansion
The expansion cohort will include up to 40 evaluable patients at a proposed RP2D level of AMXT1501 and DFMO defined by AMXT1501-101A study to further characterize safety at proposed RP2D dose level with repeat dosing, and characterize early anti-tumor activity.
干预措施: AMXT1501 (Drug)
Expansion
The expansion cohort will include up to 40 evaluable patients at a proposed RP2D level of AMXT1501 and DFMO defined by AMXT1501-101A study to further characterize safety at proposed RP2D dose level with repeat dosing, and characterize early anti-tumor activity.
干预措施: DFMO (Drug)
结局指标
主要结局
Determine safety and tolerability of AMXT1501 in combination with IV DFMO
时间窗: 1 year
To evaluate the safety and tolerability of AMXT1501 and IV DFMO combination in patients through collecting the number of patients with Treatment Related Adverse Events that occur in patients from first dose, AEs assessed by CTCAEv5.0
Determine DLTs and RP2Ds in AMXT 1501 in combination with IV DFMO
时间窗: 1 year
Indicate Number of patients with DLTs in AMXT1501 in combination with IV DFMO in patients with advanced cancer to determine the RP2D within the duration of the dose escalation period of the study as defined by the DLT definition of the protocol from baseline to end of Cycle 1
次要结局
- Characterize investigator defined response Overall Response Rate (ORR) using RECIST v1.1(6 months)
- Characterize investigator defined Duration of Response (DOR)(6 months)
- Determine the PK using AUC of AMXT 1501 and IV DFMO(6 months)
- Determine the PK using Cmax of AMXT 1501 and IV DFMO(6 months)
- Characterize AMXT1501 and IV DFMO on the expression of immune related gene signatures(1 year)