A Randomized-Controlled Three-arm Phase II Study of Lurbinectedin (PM01183) Alone or In Combination With Gemcitabine and a Control Arm With Docetaxel as Second-Line Treatment in Unresectable Non-Small Cell Lung Cancer (NSCLC) Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 69
- 主要终点
- Progression-free Survival Rate at Four Months (PFS4)
研究概览
简要总结
A clinical study of lurbinectedin(PM01183) alone or in combination with gemcitabine in comparison to docetaxel for the treatment of unresectable non-small cell lung cancer (NSCLC)patients
详细描述
A randomized-controlled, three-arm, phase II study of lurbinectedin (PM01183) alone or in combination with gemcitabine and a control arm with docetaxel as second-line treatment in unresectable non-small cell lung cancer (NSCLC)patients to evaluate the antitumor activity as progression-free survival at four months (PFS4) of PM01183 alone or in combination with gemcitabine as using single agent docetaxel as a reference in the control arm as current standard of care and to analyze overall survival (OS), overall survival rate at 1-year (OS12), duration of response (DR), antitumor activity, as response rate (RR), safety and efficacy profiles of PM01183 alone and in combination with gemcitabine, to be preliminary compared with docetaxel, patients' quality of life (QoL), pharmacokinetics (PK) of PM01183, pharmacokinetic/pharmacodynamic (PK/PD)correlation and pharmacogenomics (PGx)to explore potential correlations between clinical outcomes and molecular parameters found in tumor and blood samples
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Histologically or cytologically confirmed unresectable NSCLC
- •Patients must have failed one prior line of CT-based therapy for unresectable disease
- •Age between 18 and 75 years
- •Eastern Cooperative Oncology Group (ECOG)performance status (PS) ≤ 1
- •Adequate hematological, renal, metabolic and hepatic function
- •At least three weeks since the last prior therapy, at least four weeks since completion of any prior radiotherapy
- •Negative pregnancy test for pre-menopausal women
排除标准
- •Concomitant diseases/conditions as unstable angina, myocardial infarction, symptomatic congestive heart failure or asymptomatic with left ventricular ejection fraction (LVEF) ≤ 50%, dyspnea, infection by human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, active uncontrolled infection, pleural or pericardial effusions, myopathy, limitation of the patient's ability to comply with the treatment or to follow-up the protocol, any other major illness
- •Histological features of neuroendocrine or bronchioalveolar differentiation.
- •Unknown epidermal growth factor receptor (EGFR)mutation status or previously known EGFR mutated status in patients with adenocarcinoma.
- •Prior or concurrent invasive malignant disease, unless in complete remission for more than three years.
- •Significant cancer-related weight loss (≥10%)within four weeks prior to treatment start
- •Prior treatment with docetaxel-containing therapy
- •Symptomatic, steroid-requiring or progressive central nervous system (CNS) involvement
- •Paraneoplastic syndromes
研究组 & 干预措施
A - docetaxel
75 mg/m2 docetaxel day 1, 1-hour intravenous, every three weeks
干预措施: Docetaxel (Drug)
B - lurbinectedin (PM01183)
3.2 mg/m2 PM01183, day 1, 1-hour intravenous, every three weeks
干预措施: Lurbinectedin (PM01183) (Drug)
C - gemcitabine + lurbinectedin (PM01183)
800 mg/m2 gemcitabine / 1.6 mg/m2 PM01183 both on day 1 and day 8, 30-minutes gemcitabine/1-hour PM01183 intravenous, every three weeks
干预措施: Gemcitabine (Drug)
C - gemcitabine + lurbinectedin (PM01183)
800 mg/m2 gemcitabine / 1.6 mg/m2 PM01183 both on day 1 and day 8, 30-minutes gemcitabine/1-hour PM01183 intravenous, every three weeks
干预措施: Lurbinectedin (PM01183) (Drug)
结局指标
主要结局
Progression-free Survival Rate at Four Months (PFS4)
时间窗: At month four after patient inclusion
The rate estimate of the percentage of patients who are alive and progression-free at 16 weeks (\~4 months) after randomization. Progession disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
次要结局
- Overall Response Rate(Time from the date of randomization until 30±7 days after the last treatment infusion, assessed up to 3 years)
- Objective Response Per RECIST v.1.1(Time from the date of randomization until 30±7 days after the last treatment infusion, assessed up to 3 years)
- Duration of Response(The time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented, up to 3 years)
- Overall Survival (OS)(From the date of first infusion to the date of death or last contact, up to 12 months after last patient inclusion)
- Information on Quality of Life (QoL)(Baseline, Cycle 3 (~9 weeks), Cycle 6 (~18 weeks) and Cycle 9 (~27 weeks))
- Progression-free Survival(Time from the date of randomization to the date of PD, death (of any cause), or last tumor evaluation, whichever came first, assessed up to 3 years)
- Progression-free Survival Rate at Six Months (PFS6)(At month six after patient inclusion)