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临床试验/NCT02697058
NCT02697058已完成2 期

Phase II Randomized Study of BAX2398 in Combination With 5-Fluorouracil and Calcium Levofolinate in Japanese Patients With Metastatic Pancreatic Cancer, Which Progressed or Recurred After Prior Gemcitabine-Based Therapy

Institut de Recherches Internationales Servier16 个研究点 分布在 1 个国家目标入组 84 人开始时间: 2016年3月30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
2 期
状态
已完成
入组人数
84
试验地点
16
主要终点
Progression Free Survival (PFS) in Part 2 of Study
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

Study Part 1: To assess the safety and tolerability, and to characterize the pharmacokinetics (PK) of BAX2398 in combination with 5-FU/calcium levofolinate in Japanese patients.

Study Part 2: To compare the efficacy of BAX2398 in combination with 5-FU/calcium levofolinate versus 5-FU/calcium levofolinate as assessed by Progression Free Survival (PFS) using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Factorial
主要目的
Treatment
盲法
None

入排标准

年龄范围
20 Years 至 —（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Participant is ≥20 years of age at the time of screening.
  • •Histologically or cytologically confirmed adenocarcinoma of exocrine pancreas
  • •Documented metastatic disease
  • •Metastatic disease with at least one measurable lesion as defined by RECIST 1.1 guidelines
  • •Documented disease progression after prior gemcitabine or any gemcitabine containing therapy but excluding irinotecan, for locally advanced or metastatic setting. Prior chemotherapy must be stopped for at least 21 days before the first dose.
  • •Karnofsky Performance Status (KPS) ≥70
  • •Adequate bone marrow reserves
  • •Adequate hepatic function
  • •Adequate renal function
  • •Normal ECG including Fridericia corrected QT interval (QTcF) <440 ms within 7 days prior to first dose of study drug
  • •Recovered from the effects of any prior surgery, radiotherapy or other anti-neoplastic therapy with no residual adverse events (AEs) of Grade ≥
  • •Able to understand and sign an informed consent (or have a legal representative who is able to do so)
  • •If female of childbearing potential, participant presents with a negative pregnancy, and agrees to employ adequate birth control measures during the study dosing period and for 3 months following the last dose of study drug.
  • •Participant is willing and able to comply with the requirements of the protocol.

排除标准

  • •Active and uncontrolled central nervous system (CNS) metastases; for controlled CNS metastases, patient should have been off steroids for at least 28 days prior to starting study therapy.
  • •History of any second malignancy in the last 5 years; participants with prior history of in-situ cancer or basal or squamous cell skin cancers are eligible. Participants with other malignancies are eligible if they have been continuously disease free for at least 5 years.
  • •Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before inclusion.
  • •Cannot stop medications that are potent CYP3A4 inducers within 2 weeks and inhibitors within 1 week before start of treatment.
  • •Significant cardiac conduction abnormalities, including a history of long QTcF syndrome and/or pacemaker.
  • •New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure.
  • •Active infection, including active hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV, or an unexplained fever >38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, patients with tumor fever may be enrolled), which in the investigator's opinion might compromise the patient's participation in the trial or affect the study outcome.
  • •Known hypersensitivity to any of the components of BAX2398, other liposomal products, fluoropyrimidines, or calcium levofolinate.
  • •Any other medical or social condition deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
  • •Participant has been exposed to an investigational product (IP) within 30 days prior to the first dose of the study drug or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
  • •Participant is a family member or employee of the investigator.
  • •Participant is pregnant or lactating at the time of enrollment. Lactating mothers can resume breast feeding 30 days following the last dose of the study treatment.

研究组 & 干预措施

Part 1: Safety and PK

Experimental

BAX2398 in combination with 5-FU/calcium levofolinate

干预措施: BAX2398 + 5-FU/calcium levofolinate (Biological)

Part 2: Safety, PK, Efficacy

Experimental

BAX2398 in combination with 5-FU/calcium levofolinate

干预措施: BAX2398 + 5-FU/calcium levofolinate (Biological)

Part 2: 5-FU/calcium levofolinate alone

Active Comparator

5-FU/calcium levofolinate

干预措施: 5-FU/calcium levofolinate (Drug)

结局指标

主要结局

Progression Free Survival (PFS) in Part 2 of Study

时间窗: Part 2 Baseline to the end of the study (up to 22 months)

Progression Free Survival (PFS) was defined as the time from randomization to the first documented disease progression based on the independent central review board's assessment using RECIST 1.1 or death due to any cause, whichever occurred first.

次要结局

  • Overall Survival (OS)(Baseline to the end of the study (up to 22 months))
  • Time to Treatment Failure (TTF)(Baseline to the end of the study (up to 22 months))
  • Progression Free Survival (PFS) in Part 1 of Study(Part 1 Baseline to the end of the study (up to 22 months))
  • Disease Control Rate (DCR)(Baseline to the end of the study (up to 22 months))
  • Tumor Marker Response(Baseline, every 6 weeks and 37 days post last visit (up to 22 months))
  • Objective Response Rate (ORR)(Baseline to the end of the study (up to 22 months))
  • Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores(Baseline, Day 1 of Cycle 4, 7, 10, 13, and 16; and 37 days post last visit (up to 22 months))
  • Change From Baseline in Pain(Baseline, Days 1 and 8 of Cycles 1, 2, 4, 5, 7, 8, 10, 11, 13, 14, 16, 17, Day 1 of Cycles 3, 6, 9, 12, 15, 18 and 37 days post last visit (up to 22 months))
  • Change from Baseline in Analgesic use(Baseline, Days 1 and 8 of Cycles 1, 2, 4, 5, 7, 8, 10, 11, 13, 14, 16, 17, Day 1 of Cycles 3, 6, 9, 12, 15, 18 and 37 days post last visit (up to 22 months))
  • Number of Participants With Karnofsky Performance Score (KPS)(Baseline, Day 1 of Cycles 1 - 18 and 37 days post last visit (up to 22 months))
  • Change From Baseline in Weight(Baseline, Days 1 and 8 of Cycles 1, 2, 4, 5, 7, 8, 10, 11, 13, 14, 16, 17, Day 1 of Cycles 3, 6, 9, 12, 15, 18 and 37 days post last visit (up to 22 months))
  • Number of Participants With Clinically Significant Changes in Twelve-lead Electrocardiogram (ECG)(From start of study treatment up to 22 months)
  • Number of Participants With Serious Adverse Events(From start of study treatment up to 22 months)
  • Number of Participants With Non-Serious Adverse Events(From start of study treatment up to 22 months)
  • Number of Participants With Clinically Significant Findings From the Physical Examination(From start of study treatment up to 22 months)
  • Number of Participants With Clinically Significant Changes in Vital Signs(From start of study treatment up to 22 months)
  • Number of Participants With Clinically Significant Changes in Laboratory Results(From start of study treatment up to 22 months)
  • Maximum Plasma Concentration (Cmax) of Total Irinotecan in Study Part 1(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)
  • Maximum Plasma Concentration (Cmax) of Total Primary Metabolite of Irinotecan (SN-38) in Study Part 1(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)
  • Maximum Plasma Concentration (Cmax) of SN-38-Glucuronide (SN-38G) in Study Part 1(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)
  • Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) of Total Irinotecan in Study Part 1(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)
  • Time of Maximum Concentration (tmax) of Total Irinotecan, Total SN-38, and SN-38-Glucuronide (SN-38G) in Study Part 1(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)
  • Terminal Half-Life (t1/2) of Total Irinotecan, Total SN-38, and SN-38-Glucuronide (SN-38G) in Study Part 1(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)
  • Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) of Total SN-38 in Study Part 1.(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)
  • Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) of SN-38-Glucuronide (SN-38G) IN Study Part 1.(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)
  • Systemic Clearance (CL) of Total Irinotecan in Study Part 1(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)
  • Systemic Clearance (CL) of Total SN-38 in Study Part 1(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)
  • Systemic Clearance (CL) of SN-38-Glucuronide (SN-38G) in Study Part 1(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)
  • Volume of Distribution at Steady-state (Vss) of Total SN-38 in Study Part 1(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)
  • Volume of Distribution (V) of Total Irinotecan in Study Part 1(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)
  • Volume of Distribution (V) of Total SN-38 in Study Part 1.(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)
  • Volume of Distribution (V) of SN-38-Glucuronide (SN-38G) in Study Part 1.(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)
  • Volume of Distribution at Steady-State (Vss) of Total Irinotecan in Study Part 1(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)
  • Area Under the Curve (AUC) - Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)(Cycle 1: pre dose, 15-90 minutes after start of infusion; and 0-6, 6-24, 24-48, 72-168, and 216-264 hours after the end of the infusion; Cycle 2: pre dose)
  • Systemic Clearance (CL) -Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)(Cycle 1: pre dose, 15-90 minutes after start of infusion; and 0-6, 6-24, 24-48, 72-168, and 216-264 hours after the end of the infusion; Cycle 2: pre dose)
  • Volume of Distribution (V)-Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)(Cycle 1: pre dose, 15-90 minutes after start of infusion; and 0-6, 6-24, 24-48, 72-168, and 216-264 hours after the end of the infusion; Cycle 2: pre dose)
  • Volume of Distribution at Steady-State (Vss)-Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)(Cycle 1: pre dose, 15-90 minutes after start of infusion; and 0-6, 6-24, 24-48, 72-168, and 216-264 hours after the end of the infusion; Cycle 2: pre dose)
  • Terminal Half-life (t1/2) - Total Irinotecan, SN-38, and SN-38-Glucuronide (SN-38G)(Cycle 1: pre dose, 15-90 minutes after start of infusion; and 0-6, 6-24, 24-48, 72-168, and 216-264 hours after the end of the infusion; Cycle 2: pre dose)
  • Volume of Distribution at Steady-state (Vss) of SN-38-Glucuronide (SN-38G) in Study Part 1(Cycle 1: pre dose, 30, 60, 90 minutes after start of infusion and 1, 3, 9, 24, 36, 48, 72, 120 and 168 hours after the end of the infusion; Cycle 2: pre dose)

研究者

申办方类型
Other
责任方
Sponsor

研究点 (16)

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