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临床试验/NCT03116971
NCT03116971终止1 期

A Multicenter Study With an Open Label Phase Ib Part Followed by a Randomized, Placebo-controlled, Double-blind, Phase II Part to Evaluate Efficacy, Safety, Tolerability, and PK of M3814 in Combination With Etoposide and Cisplatin in Subjects With Treatment-naïve Small Cell Lung Cancer (SCLC) Extensive Disease (ED)

EMD Serono Research & Development Institute, Inc.7 个研究点 分布在 3 个国家目标入组 2 人开始时间: 2017年5月25日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
1 期
状态
终止
入组人数
2
试验地点
7
主要终点
Phase Ib: Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) over the DLT period.
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

M3814 is an investigational drug under evaluation for treatment of lung cancer. The purpose of the study was to assess the Safety and Efficacy of M3814 in combination with chemotherapy with SCLC ED.

详细描述

The study was intended to be a phase I/II trial, but the study never moved forward to Phase II due to recruitment challenges.

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
Double (Participant, Investigator)

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

  • •To be eligible for the study (Phase Ib and Phase II) the participant must fulfill all of the following criteria:
  • •Male or female participants at least 18 years of age
  • •Histological or cytological diagnosis of SCLC
  • •Extensive disease (ie, disease beyond ipsilateral hemithorax, which may include malignant pleural or pericardial effusion or hematogenous metastases [Tany, Nany, M1a/b; T3-T4, Nany, M0, due to multiple lung nodules or extent of disease that precludes a tolerable radiation field, as judged by the Investigator])
  • •Participants eligible for first line platinum-based chemotherapy
  • •Measurable or evaluable disease according to RECIST v1.1
  • •Eastern Cooperative Oncology Group performance status (ECOG PS) less than equals to (<=) 2
  • •Life expectancy of greater than equals to (≥) 3 months
  • •Female participants of childbearing potential and male participants with female partners of childbearing potential must be willing to avoid pregnancy Note: Other protocol defined criteria could apply.

排除标准

  • •Participants are not eligible for the study if they fulfill any of the following exclusion criteria:
  • •Prior anticancer therapy for extensive disease (ED) SCLC including experimental agents.
  • •Concurrent use of other anticancer therapy including any investigational agent within 28 days prior to the first dose of the investigational drug M
  • •Extensive prior radiotherapy (RT) on more than 30% of bone marrow reserves (by Investigator judgment)
  • •Prior bone marrow/stem cell transplantation within 5 years before study start (Phase II only)
  • •Major surgical intervention within 28 days prior to the first dose of investigational drug administration. Intervention(s) to establish the diagnosis for SCLC is permitted within 28 days as long as participants are cleared by the medical and surgical teams.
  • •Poor vital organ functions defined as:
  • •Bone marrow impairment as evidenced by hemoglobin less than (<) 9.0 gram per deci liter (g/dL) (5.7 micromole per liter (μmol/L)), absolute neutrophil count < 1.5 × 109/L, platelets < 100 × 109/L
  • •Renal impairment as evidenced by calculated creatinine clearance < 60 mL/minutes (min) (according to the Cockcroft-Gault formula)
  • •Liver function abnormality as defined by total bilirubin greater than (>) 1.5 × upper limit of normal (ULN) or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2.5 × ULN (participants with liver involvement: a maximum of AST/ALT 5 × ULN)
  • •Contraindication to the use of etoposide or cisplatin
  • •Participants currently receiving (or unable to stop using prior to receiving the first dose of investigational drug) medications or herbal supplements known to be potent inhibitors of cytochrome P450 (CYP) 3A and CYP2C19 (unless treatment can be discontinued at least 1 week prior to receiving the first dose of investigational drug) or potent inducers of CYP3A and CYP2C19 (unless treatment can be discontinued at least 3 weeks prior to receiving the first dose of investigational drug). Note: Other protocol defined criteria could apply.

研究组 & 干预措施

M3814 PiC with Etoposide and Cisplatin

Experimental

Participants received M3814 100 milligram (mg) powder in capsule (PiC) orally once daily in combination with Etoposide 100 mg/m^2 over a 60 minute intravenous infusion on Days 1-3 and Cisplatin 75 milligram per square meter (mg/m^2) over a 60-minute intravenous infusion on Day 1 for 6 cycles with each cycle lasting 3 weeks (21 days) until progressive disease (PD).

干预措施: M3814 (Drug)

M3814 PiC with Etoposide and Cisplatin

Experimental

Participants received M3814 100 milligram (mg) powder in capsule (PiC) orally once daily in combination with Etoposide 100 mg/m^2 over a 60 minute intravenous infusion on Days 1-3 and Cisplatin 75 milligram per square meter (mg/m^2) over a 60-minute intravenous infusion on Day 1 for 6 cycles with each cycle lasting 3 weeks (21 days) until progressive disease (PD).

干预措施: Cisplatin (Drug)

M3814 PiC with Etoposide and Cisplatin

Experimental

Participants received M3814 100 milligram (mg) powder in capsule (PiC) orally once daily in combination with Etoposide 100 mg/m^2 over a 60 minute intravenous infusion on Days 1-3 and Cisplatin 75 milligram per square meter (mg/m^2) over a 60-minute intravenous infusion on Day 1 for 6 cycles with each cycle lasting 3 weeks (21 days) until progressive disease (PD).

干预措施: Etoposide (Drug)

M3814 (HME Tablet + PiC) with Etoposide and Cisplatin

Experimental

Participants received M3814 100 mg hot melt extrusion (HME) tablet orally 5 days prior to Day 1 and M3814 100 mg PiC, orally once daily from Day 1 in combination with Etoposide 100 mg/m^2 over a 60 minute intravenous infusion on Days 1-3 and Cisplatin 75 mg/m^2 over a 60-minute intravenous infusion on Day 1 for 6 cycles with each cycle lasting 3 weeks (21 days) until PD.

干预措施: M3814 (Drug)

M3814 (HME Tablet + PiC) with Etoposide and Cisplatin

Experimental

Participants received M3814 100 mg hot melt extrusion (HME) tablet orally 5 days prior to Day 1 and M3814 100 mg PiC, orally once daily from Day 1 in combination with Etoposide 100 mg/m^2 over a 60 minute intravenous infusion on Days 1-3 and Cisplatin 75 mg/m^2 over a 60-minute intravenous infusion on Day 1 for 6 cycles with each cycle lasting 3 weeks (21 days) until PD.

干预措施: Cisplatin (Drug)

M3814 (HME Tablet + PiC) with Etoposide and Cisplatin

Experimental

Participants received M3814 100 mg hot melt extrusion (HME) tablet orally 5 days prior to Day 1 and M3814 100 mg PiC, orally once daily from Day 1 in combination with Etoposide 100 mg/m^2 over a 60 minute intravenous infusion on Days 1-3 and Cisplatin 75 mg/m^2 over a 60-minute intravenous infusion on Day 1 for 6 cycles with each cycle lasting 3 weeks (21 days) until PD.

干预措施: Etoposide (Drug)

结局指标

主要结局

Phase Ib: Number of Subjects Experienced Any Dose-Limiting Toxicity (DLT) over the DLT period.

时间窗: up to 21 days

Phase Ib: Determination of Recommended Phase II dose (RP2D) of Escalating Dose of M3814 in Combination With Cisplatin and Etoposide for the Phase II Part of the Study

时间窗: up to 11 months

Phase II: Progression Free Survival (PFS) as Assessed by the Investigator according to RECIST v1.1

时间窗: Time from randomization to first assessment of disease progression or death, whichever is earlier, assessed up to 24 months

PFS time will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. The PFS time is defined as the duration from randomization to either first observation of progressive disease (PD) or occurrence of death due to any cause.

次要结局

  • Phase Ib: Number of Subjects with of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths(From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment)
  • Phase Ib: Number of Subjects with Abnormal Laboratory Values, Abnormal Vital Signs and Abnormal Electrocardiograms (ECGs)(From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment)
  • Phase Ib: Change in Eastern Cooperative Oncology Group performance status (ECOG PS)(From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment)
  • Phase Ib: Percentage of Subjects with Objective Response (OR) According to RECIST v1.1(Post randomization with period tumor evaluations until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy, assessed up to 11 months)
  • Phase Ib: Duration of Response (DoR) According to RECIST v1.1(First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 11 months)
  • Phase Ib: Percentage of Subjects With Disease Control(First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 11 months)
  • Phase Ib: Progression Free Survival (PFS) According to RECIST v1.1(Time from randomization to first assessment of disease progression or death, whichever is earlier, assessed up to 11 months)
  • Phase Ib: Overall Survival (OS)(Time from randomization to death due to any cause, assessed up to 11 months)
  • Phase Ib: Area under the concentration-time curve from 0 to 4 hours (AUC 0-4), 0 to 24 hours (AUC 0-24) for M3814, Cisplatin and Etoposide(Day (D) -1, Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hours (hrs) post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose, C3D1 Pre-dose and 3.5 hrs post dose)
  • Phase Ib: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUC 0-t ) for M3814, Cisplatin and Etoposide(Day (D) -1, Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose)
  • Phase Ib: Maximum Observed Plasma Concentration (Cmax) for M3814, Cisplatin and Etoposide(Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post-dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post-dose, C2D3 Pre-dose)
  • Phase Ib: Time to Reach Maximum Plasma Concentration (Tmax) for M3814, Cisplatin and Etoposide(Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post-dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post-dose, C2D3 Pre-dose)
  • Phase Ib: Apparent Terminal Half-life (t1/2) for M3814(C1D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hours (hrs) post-dose)
  • Phase Ib: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of M3814(C1D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hours (hrs) post-dose)
  • Phase Ib: Changes in Cmax for Cisplatin From C1D1 and C2D1(Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose)
  • Phase II: Overall Survival (OS)(Time from randomization to death due to any cause, assessed up to 24 months)
  • Phase Ib: Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of M3814(Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post-dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post-dose, C2D3 Pre-dose)
  • Phase Ib: Intravenous (IV) Clearance (CL) of Cisplatin and Etoposide(Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hr post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose)
  • Phase Ib: Apparent Volume of Distribution Following Extravascular Administration (Vz/f) of M3814(Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose)
  • Phase Ib: Apparent Volume of Distribution (Vz) of Cisplatin and Etoposide(Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose)
  • Phase Ib: Terminal rate constant (λz) for M3814, Cisplatin and Etoposide(Day (D) -1, C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose)
  • Phase Ib: Changes in Cmax for M3814 Between Day -1 and C2D1(Day (D) -1, Cycle (C) 2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose)
  • Phase Ib: Changes in AUC for M3814 Between Day -1 and C2D1(Day (D) -1, Cycle (C) 2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose)
  • Phase Ib: Changes in AUC for Etoposide From C1D1 to C1D2, C1D3, and C2D1 (for the first 2 dose levels), or From C1D1 to C2D1 (other dose levels)(Day (D) -1, Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose)
  • Phase Ib: Changes in Cmax for Etoposide From C1D1 and C2D1(Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose)
  • Phase Ib: Changes in AUC for Cisplatin From C1D1 to C1D2, C1D3, and C2D1 (for the first 2 dose levels), or From C1D1 to C2D1 (other dose levels)(Day (D) -1, Cycle (C) 1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5 (excluding D-1), 4, 6 and 8 hours (hrs) post dose)
  • Phase II: Percentage of Subjects with Objective Response (OR) According to RECIST v1.1(Post randomization every 6 weeks up to Week 54 and then every 12 weeks until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy., assessed up to 24 months)
  • Phase II: Duration of Response (DoR) According to RECIST v1.1(First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 24 months)
  • Phase II: Percentage of Subjects With Disease Control(First documented complete response or partial response, whichever is first recorded until the first assessment of disease progression, assessed up to 24 months)
  • Phase II: Percentage of Subjects Who Received Prophylactic Cranial Irradiation (PCI) and/or Thorax Irradiation After 6 Cycles of Treatment(After 6 Cycles of treatment, assessed up to 24 months)
  • Phase II: Tumor shrinkage From Baseline in target lesions(Post randomization every 6 weeks up to Week 54 and then every 12 weeks until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy., assessed up to 24 months)
  • Phase II: Number of subjects with of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths(From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment)
  • Phase II: Number of Subjects with Abnormal Laboratory Values, Abnormal Vital Signs and Abnormal Electrocardiograms (ECGs)(From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment)
  • Phase II: Change in Eastern Cooperative Oncology Group performance status (ECOG PS)(From the first dose of study drug treatment up to 30 days after the last dose of study drug treatment)
  • Phase II: Primary Health-Related Quality of Life (HRQoL) Based on Time to Definitive Deterioration (TUDD) as Assessed Using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30)(Screening; Post randomization every 6 weeks up to Week 54 and then every 12 weeks until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy., assessed up to 24 months)
  • Phase II: Primary HRQoL based on TUDD Assessed Using EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13)(Screening; Post randomization every 6 weeks up to Week 54 and then every 12 weeks until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy., assessed up to 24 months)
  • Phase II: Primary HRQoL based on TUDD Assessed Using European Quality of Life 5- dimensions questionnaire (EQ-5D)(Screening; Post randomization every 6 weeks up to Week 54 and then every 12 weeks until disease progression or subject withdrawal of consent, irrespective of treatment discontinuation or initiation of another therapy., assessed up to 24 months)
  • Phase II: Area under the concentration-time curve from 0 to 24 hours (AUC 0-24) for M3814, Cisplatin and Etoposide(C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose)
  • Phase II: Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC 0-t ) for M3814, Cisplatin and Etoposide(C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose)
  • Phase II: Maximum Observed Plasma Concentration (Cmax) for M3814, Cisplatin and Etoposide(C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose)
  • Phase II: Time to Reach Maximum Plasma Concentration (Tmax) for M3814, Cisplatin and Etoposide(C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose)
  • Phase II: Apparent Terminal Half-life (t1/2) for M3814(C1D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose)
  • Phase II: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of M3814(C1D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose)
  • Phase II: Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of M3814(C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose)
  • Phase II: Intravenous (IV) Clearance (CL) of Cisplatin and Etoposide(Time Frame: C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose)
  • Phase II: Apparent Volume of Distribution Following Extravascular Administration (Vz/f) of M3814(C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose)
  • Phase II: Apparent Volume of Distribution (Vz) of Cisplatin and Etoposide(C1D1, C2D1: Pre-dose, 0.5, 1, 1.5, 2, 3, 3.5, 4, 6 and 8 hrs post dose; C1D2 Pre-dose, C1D3 Pre-dose, C1D8 Pre-dose, C1D15 Pre-dose and 2 hrs post dose, C2D3 Pre-dose)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (7)

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