Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of Lurbinectedin (PM01183) in Combination With Weekly Paclitaxel, With or Without Bevacizumab, in 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
- 69
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
Clinical trial of PM01183 in combination with paclitaxel, with or without bevacizumab, in patients with solid tumors
详细描述
Clinical trial to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 in combination with weekly paclitaxel, with or without bevacizumab. Once a recommended dose is defined for the PM01183 and weekly paclitaxel combination, the feasibility of adding bevacizumab to this combination will be explored in a selected cohort of patients to characterize the safety profile and feasibility of this combination, to obtain preliminary information on antitumor activity, to obtain preliminary information on quality of life (QoL), to characterize the pharmacokinetics (PK) of this combination and to detect major drug-drug PK interactions and PK(pharmacokinetic)/PD(pharmacodynamic) correlation and to conduct an exploratory pharmacogenomic(PGx) analysis in patients with selected advanced solid tumors.
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 signed and dated written informed consent
- •Age between 18 and 75 years old (both inclusive)
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 1
- •Life expectancy ≥ 3 months.
- •Patients with a histologically/cytologically confirmed diagnosis of advanced and/or unresectable disease of any of the following tumors:
- •Breast cancer
- •Epithelial ovarian cancer or gynecological cancer
- •Head and neck squamous cell carcinoma
- •Non-small cell lung cancer
- •Small cell lung cancer
- •Platinum-refractory germ-cell tumors.
- •Adenocarcinoma or carcinoma of unknown primary site
- •Adequate bone marrow, renal, hepatic, and metabolic function
- •Recovery to grade ≤ 1 or to baseline from any Adverse Event (AE) derived from previous treatment (excluding alopecia of any grade).
- •Pre-menopausal women must have a negative pregnancy test before study entry and agree to use a medically acceptable method of contraception throughout the treatment period and for at least six weeks after treatment discontinuation
排除标准
- •Prior treatment with PM01183 or weekly paclitaxel or nanoalbumin-paclitaxel
- •Patients who have previously discontinued paclitaxel-based regimes due to drug related toxicity.
- •Known hypersensitivity to bevacizumab or any component of its formulation
- •Patients who have previously discontinued bevacizumab-containing regimes due to drug-related toxicity.
- •More than three prior lines of chemotherapy
- •Less than three months since last taxane-containing therapy.
- •Wash-out period:
- •Less than three weeks since the last chemotherapy-containing regimen
- •Less than three weeks since the last radiotherapy dose
- •Less than four weeks since last monoclonal antibody-containing therapy
- •Concomitant diseases/conditions:
- •Unstable angina, myocardial infarction, valvular heart disease, encephalopathy, ischemic attacks, hemorrhagic or ischemic cerebrovascular accident (CVA) or ongoing pulmonary embolism within last year, arrhythmia, hepatopathy, uncontrolled infection, hemoptysis or oxygen requiring dyspnea, known HIV infection, bleeding risk, muscular problems, peripheral neuropathy, Symptomatic or progressive brain metastases or leptomeningeal disease.
- •Men or pre-menopausal women who are not using an effective method of contraception as previously described; actively breast feeding women.
- •Patients who have pelvic irradiation with doses ≥ 45 Grays (Gy).
- •History of previous bone marrow and/or stem cell transplantation.
- •Confirmed bone marrow involvement
研究组 & 干预措施
Treatment
PM01183 + paclitaxel +/- bevacizumab
干预措施: PM01183 + paclitaxel +/- bevacizumab (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: The MTD was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)
The MTD will be the lowest level at which one third or more evaluable patients experience a DLT in Cycle 1. DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1.
Recommended Dose (RD)
时间窗: The RD was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)
The RD will be the highest DL explored with less than one third of the patients experiencing a DLT during Cycle 1. DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1.
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
时间窗: DLT was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks)
DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1.
次要结局
- Best Tumor Response(Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks))
- Progression-free Survival(Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks))
- Duration of Response (DR)(Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks))
- Quality of Life (QoL)(Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks))