Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of Lurbinectedin (PM01183) in Combination With Cisplatin in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 41
- 主要终点
- Recommended dose (RD) of the combination PM01183 and cisplatin
研究概览
简要总结
Clinical and Pharmacokinetic Study of Lurbinectedin (PM01183) in Combination with Cisplatin in Patients with Advanced Solid Tumors to determine the recommended dose (RD) of PM01183 in combination with cisplatin, to characterize the safety profile, the pharmacokinetics (PK) of this combination, to obtain preliminary information on the clinical antitumor activity and to conduct an exploratory pharmacogenomic (PGx) analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Voluntarily signed written informed consent
- •Age ≥ 18 years old
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤
- •Life expectancy ≥ 3 months.
- •Patients with confirmed diagnosis of advanced solid tumors.
- •Patients may have received ≤ 2 chemotherapy-containing lines in the advanced setting.
- •Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤ seven days before inclusion in the study)
- •Recovery or stabilization to grade ≤ 1 from any adverse event derived from previous treatment (up to grade 2 alopecia or asthenia/fatigue are allowed).
- •No clinically significant changes in ECG.
- •At least four weeks since the last monoclonal antibody containing therapy or definitive radiotherapy (RT)
- •At least two weeks since the last biological/investigational single-agent therapy (excluding MAbs) and/or palliative RT (≤10 fractions or ≤30 Gy total dose)
- •Fertil women must have pregnancy excluded by appropriate testing before study entry
排除标准
- •Prior treatment with PM01183 or trabectedin.
- •Concomitant diseases/conditions:
- •History within the last year or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically relevant valvular heart disease or symptomatic arrhythmia or any asymptomatic ventricular arrhythmia requiring ongoing treatment.
- •Ongoing, non-neoplastic, chronically active liver disease of any origin.
- •Active infection.
- •Patients who are requiring any ongoing oxygen support.
- •Known human immunodeficiency virus (HIV) infection.
- •Any other major illness.
- •Symptomatic or corticosteroid-requiring brain metastases or leptomeningeal disease involvement. Patients with asymptomatic documented stable brain metastases not requiring corticosteroids during the last three months are allowed.
- •Peripheral sensory/motor neuropathy grade >
- •Hearing impairment grade >
- •Fertile men or women not using an effective method of contraception.
- •History of bone marrow or stem cell transplantation
- •Radiotherapye to >35% of the bone marrow.
研究组 & 干预措施
lurbinectedin (PM01183) / cisplatin
Patients will receive cisplatin as a 90-min i.v. infusion. In addition, patients will receive PM01183 as an i.v. infusion over 1-hour.
干预措施: lurbinectedin (PM01183) (Drug)
lurbinectedin (PM01183) / cisplatin
Patients will receive cisplatin as a 90-min i.v. infusion. In addition, patients will receive PM01183 as an i.v. infusion over 1-hour.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Recommended dose (RD) of the combination PM01183 and cisplatin
时间窗: 30 months
To determine the recommended dose (RD) of PM01183 in combination with cisplatin every three weeks (q3wk) with or without aprepitant in patients with advanced solid tumors. The RD will be the dose level (DL) immediately below the maximum tolerated dose (MTD), that is, the highest DL explored at which less than one third of evaluable patients experience a DLT during Cycle 1.
次要结局
- Pharmacokinetics (PK) characterisation of Cmax (maximum concentratio), AUC (area under the curve), CL (clearance), HL (half life) y Vss (volume of distribution)(30 months)
- Pharmacogenomic (PGx) analysis(30 months)