Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM01183 in Combination With Gemcitabine in Non-heavily Pretreated Patients With Selected Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 47
- 试验地点
- 3
- 主要终点
- Recommended Dose (RD)
研究概览
简要总结
Phase I multicenter, open-label, clinical and pharmacokinetic study of PM01183 in combination with gemcitabine in non-heavily pretreated patients with selected advanced solid tumors to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 in combination with gemcitabine, to characterize the safety profile and feasibility of this combination in patients with selected advanced solid tumors, to characterize the pharmacokinetics (PK), to obtain preliminary information on the clinical antitumor activity in non-heavily pretreated selected solid tumor patients and to evaluate the pharmacogenomics (PGx) in tumor samples of patients exposed, in order to assess potential markers of response and/or resistance.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily written informed consent
- •Age: between 18 and 75 years (both inclusive)
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1
- •Life expectancy ≥ 3 months
- •Patients with a histologically/cytologically confirmed diagnosis of advanced disease of any of the following tumors:
- •Breast cancer
- •Epithelial ovarian cancer (including primary peritoneal disease and/or fallopian tube carcinomas and/or endometrial adenocarcinomas)
- •Stromal uterine sarcomas
- •Non-small cell lung cancer (NSCLC)
- •Platinum-refractory or relapsed germ cell tumors
- •Adenocarcinoma of the exocrine pancreas
- •Biliary tract adenocarcinoma
- •Adenocarcinoma or carcinoma of unknown primary site
- •Advanced or unresectable mesothelioma
- •At least three weeks since the last anticancer therapy,including radiation therapy (RT)
- •Adequate bone marrow, renal, hepatic, and metabolic function
- •Left ventricular ejection fraction (LVEF) by echocardiography (ECHO) or multiple-gated acquisition (MUGA) within normal range (according to institutional standards).
- •Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six weeks after discontinuation of treatment.
排除标准
- •Concomitant diseases/conditions:
- •History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.
- •Symptomatic or any uncontrolled arrhythmia
- •Ongoing chronic alcohol consumption, or cirrhosis
- •Active uncontrolled infection.
- •Known human immunodeficiency virus (HIV) infection.
- •Any other major illness that, in the Investigator's judgment
- •Brain metastases or leptomeningeal disease involvement
- •Men or women of childbearing potential who are not using an effective method of contraception
- •Patients who have had radiation therapy in more than 35% of the bone marrow
- •History of previous bone marrow and/or stem cell transplantation
- •Prior treatment with gemcitabine-containing therapy for advanced disease
研究组 & 干预措施
lurbinectedin (PM01183) / gemcitabine
Patients will consecutively receive the following on Days 1 and 8 q3wk (three weeks = one treatment cycle):
- Gemcitabine: intravenous infusion of 800 mg/m2/day over 30 minutes,
immediately followed by:
- PM01183: intravenous infusion over one hour at a starting dose of 2.5 mg/day, flat dose (FD), both on Days 1 and 8 every 3 weeks
干预措施: lurbinectedin (PM01183) (Drug)
lurbinectedin (PM01183) / gemcitabine
Patients will consecutively receive the following on Days 1 and 8 q3wk (three weeks = one treatment cycle):
- Gemcitabine: intravenous infusion of 800 mg/m2/day over 30 minutes,
immediately followed by:
- PM01183: intravenous infusion over one hour at a starting dose of 2.5 mg/day, flat dose (FD), both on Days 1 and 8 every 3 weeks
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Recommended Dose (RD)
时间窗: 19 months
The RD will be the highest dose level explored at which less than one third of evaluable patients experience a DLT during Cycle 1.
次要结局
- Pharmacokinetics (PK) characterisation(19 months)
- Preliminary antitumor efficacy(29 months)
- Pharmacogenomics (PGx)(29 months)