A Non-comparative Randomized Phase 2 Study, Evaluating the Efficacy of 5-FU + NALIRI and 5-FU + NALIRINOX for Metastatic Pancreatic Ductal Adenocarcinoma (PDAC), Progressive After Gemcitabine-Abraxane or Gemcitabine Monotherapy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 134
- 试验地点
- 13
- 主要终点
- Efficacy of NALIRINOX and NALIRI through Progression-Free Survival at D85
研究概览
简要总结
A non-comparative randomized phase 2 study, evaluating the efficacy of 5-FU + NALIRI and 5-FU + NALIRINOX for metastatic pancreatic ductal adenocarcinoma (PDAC), progressive after Gemcitabine-Abraxane or Gemcitabine monotherapy
详细描述
Based on the results of previous studies, the sponsor aims to assess efficacy and safety of this triplet (irinotecan, 5FU/LV and oxaliplatin) in second-line treatment in fit patients (ECOG 0-1) metastatic PDAC.
The primary objective is to assess the efficacy of NALIRINOX (= investigational arm) and NALIRI (= standard care arm) in terms of Progression-Free Survival Rate (PFSR).
As secondary objectives, the following will be evaluated in both arms:
- Safety/toxicity and tolerability profile according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.
- Progression free survival (PFS)
- Overall response rate and duration of response as assessed by imaging (RECIST 1.1) and tumor markers
- Overall survival (OS)
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven metastatic adenocarcinoma of the pancreas
- •Progression documented after gemcitabine-Abraxane, or gemcitabine monotherapy
- •Signed written informed consent
- •ECOG PS 0/1 at study entry
- •Measurable disease
- •Adequate renal (serum creatinine ≤ 1.5x upper reference range), liver (total bilirubin ≤ 1.5x upper reference range) and hematopoietic functions (PMN ≥ 1,5x109/L, platelets ≥ 100x109/L, hemoglobin ≥ 9g/dl)
- •INR/PTT ≤ 1.5x ULN
- •Life expectancy of at least 12 weeks
- •Effective contraception for both male and female patients if the risk of conception exists during treatment and for one month after the last administration
- •Peripheral Neuropathy < grade 2
排除标准
- •Uncontrolled concurrent CNS, cardiac, infectious diseases, hypertension
- •History of myocardial infarction, deep venous or arterial thrombosis, CVA during the last 6 months
- •Known hypersensitivity to any of the components, including excipients, of study treatments
- •Previous malignancy in the last past 3 years except basal cell cancer of the skin or preinvasive cancer of the cervix or carcinoma in situ of any type
- •Pregnancy or breast feeding
- •Medical or psychological conditions that would not permit the patient to complete the study or sign inform consent
- •Unstable angina, congestive heart failure ≥NYHA class II
- •Uncontrolled hypertension despite optimal management (systolic blood pressure >150 mmHg or diastolic pressure > 90mmHg)
- •HIV infection
- •Complete DPD deficiency
- •Liver failure, cirrhosis Child Pugh B or C
- •Active chronic hepatitis B or C with a need for antiviral treatment
- •Brain metastasis
- •Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to the first dose of treatment
- •History of organ allograft
- •Ongoing uncontrolled, serious infection
- •Renal failure requiring dialysis
- •Patients receiving or having received any investigational treatment within 4 weeks prior to study entry, or participating to another clinical study
研究组 & 干预措施
Arm A NALIRI
Cycle length: 14 days
Day 1:
-
Leucovorin: 400 mg/m² IV - Dilute in 250 mL DSW and administer over two hours
-
Liposomal irinotecan (FBE): 70 mg/m² IV* - Dilute in 500 mL DSW and administer over 90 min
-
5 FU: 2400 mg/m² IV - Dilute in 500 to 1000 mL 0,9% NS of DSW and administer as a continuous IV infusion over 46 hours. To accommodate an ambulatory pump for outpatient treatment can be administered undiluted (50 mg/mL) or the total dose diluted in 100 to 150 mL NS.
-
Patients who are known to be homozygous for UGT1A1*28 should start treatment with 50 mg/m2 ONIVYDE. If they do not encounter drug related toxicities during the first cycle of therapy (started at a reduced dose of 50 mg/m2), they may have the dose of ONIVYDE increased to a dose of 70 mg/m2 in subsequent cycles based on individual patient tolerance.
干预措施: Nanoliposomal irinotecan (Drug)
Arm A NALIRI
Cycle length: 14 days
Day 1:
-
Leucovorin: 400 mg/m² IV - Dilute in 250 mL DSW and administer over two hours
-
Liposomal irinotecan (FBE): 70 mg/m² IV* - Dilute in 500 mL DSW and administer over 90 min
-
5 FU: 2400 mg/m² IV - Dilute in 500 to 1000 mL 0,9% NS of DSW and administer as a continuous IV infusion over 46 hours. To accommodate an ambulatory pump for outpatient treatment can be administered undiluted (50 mg/mL) or the total dose diluted in 100 to 150 mL NS.
-
Patients who are known to be homozygous for UGT1A1*28 should start treatment with 50 mg/m2 ONIVYDE. If they do not encounter drug related toxicities during the first cycle of therapy (started at a reduced dose of 50 mg/m2), they may have the dose of ONIVYDE increased to a dose of 70 mg/m2 in subsequent cycles based on individual patient tolerance.
干预措施: 5 FU (Drug)
Arm A NALIRI
Cycle length: 14 days
Day 1:
-
Leucovorin: 400 mg/m² IV - Dilute in 250 mL DSW and administer over two hours
-
Liposomal irinotecan (FBE): 70 mg/m² IV* - Dilute in 500 mL DSW and administer over 90 min
-
5 FU: 2400 mg/m² IV - Dilute in 500 to 1000 mL 0,9% NS of DSW and administer as a continuous IV infusion over 46 hours. To accommodate an ambulatory pump for outpatient treatment can be administered undiluted (50 mg/mL) or the total dose diluted in 100 to 150 mL NS.
-
Patients who are known to be homozygous for UGT1A1*28 should start treatment with 50 mg/m2 ONIVYDE. If they do not encounter drug related toxicities during the first cycle of therapy (started at a reduced dose of 50 mg/m2), they may have the dose of ONIVYDE increased to a dose of 70 mg/m2 in subsequent cycles based on individual patient tolerance.
干预措施: Leucovorin (Drug)
Arm B NALIRINOX
Cycle length: 14 days
Day 1:
- Oxaliplatin 60 mg IV - Dilute in 500 mL D5W and administer over two hours (prior to leucovorin). Shorter oxaliplatin administration schedules (eg. 1mg/m2 per minute) appear to be safe.
- Leucovorin: 400 mg/m² IV - Dilute in 250 mL DSW and administer over two hours (after oxaliplatin)
- Nanoliposomal irinotecan (FBE): 50 mg/m² IV - Dilute in 500 mL D5W and administer over 90 min
- 5 FU: 2400 mg/m² IV - Dilute in 500 to 1000 mL 0,9% NS of DSW and administer as a continuous IV infusion over 46 hours. To accommodate an ambulatory pump for outpatient treatment can be administered undiluted (50 mg/mL) or the total dose diluted in 100 to 150 mL NS.
干预措施: Nanoliposomal irinotecan (Drug)
Arm B NALIRINOX
Cycle length: 14 days
Day 1:
- Oxaliplatin 60 mg IV - Dilute in 500 mL D5W and administer over two hours (prior to leucovorin). Shorter oxaliplatin administration schedules (eg. 1mg/m2 per minute) appear to be safe.
- Leucovorin: 400 mg/m² IV - Dilute in 250 mL DSW and administer over two hours (after oxaliplatin)
- Nanoliposomal irinotecan (FBE): 50 mg/m² IV - Dilute in 500 mL D5W and administer over 90 min
- 5 FU: 2400 mg/m² IV - Dilute in 500 to 1000 mL 0,9% NS of DSW and administer as a continuous IV infusion over 46 hours. To accommodate an ambulatory pump for outpatient treatment can be administered undiluted (50 mg/mL) or the total dose diluted in 100 to 150 mL NS.
干预措施: 5 FU (Drug)
Arm B NALIRINOX
Cycle length: 14 days
Day 1:
- Oxaliplatin 60 mg IV - Dilute in 500 mL D5W and administer over two hours (prior to leucovorin). Shorter oxaliplatin administration schedules (eg. 1mg/m2 per minute) appear to be safe.
- Leucovorin: 400 mg/m² IV - Dilute in 250 mL DSW and administer over two hours (after oxaliplatin)
- Nanoliposomal irinotecan (FBE): 50 mg/m² IV - Dilute in 500 mL D5W and administer over 90 min
- 5 FU: 2400 mg/m² IV - Dilute in 500 to 1000 mL 0,9% NS of DSW and administer as a continuous IV infusion over 46 hours. To accommodate an ambulatory pump for outpatient treatment can be administered undiluted (50 mg/mL) or the total dose diluted in 100 to 150 mL NS.
干预措施: Leucovorin (Drug)
Arm B NALIRINOX
Cycle length: 14 days
Day 1:
- Oxaliplatin 60 mg IV - Dilute in 500 mL D5W and administer over two hours (prior to leucovorin). Shorter oxaliplatin administration schedules (eg. 1mg/m2 per minute) appear to be safe.
- Leucovorin: 400 mg/m² IV - Dilute in 250 mL DSW and administer over two hours (after oxaliplatin)
- Nanoliposomal irinotecan (FBE): 50 mg/m² IV - Dilute in 500 mL D5W and administer over 90 min
- 5 FU: 2400 mg/m² IV - Dilute in 500 to 1000 mL 0,9% NS of DSW and administer as a continuous IV infusion over 46 hours. To accommodate an ambulatory pump for outpatient treatment can be administered undiluted (50 mg/mL) or the total dose diluted in 100 to 150 mL NS.
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Efficacy of NALIRINOX and NALIRI through Progression-Free Survival at D85
时间窗: at day 85 from randomization
NALIRINOX is the investigational arm and NALIRI is the standard care arm. The efficacy will be assessed in terms of the Progression-Free Survival Rate (PFSR). This is defined as the proportion of patients alive and free of progression at day 85.
次要结局
- Duration of disease control(From date of first study treatment administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years after End of Treatment)
- Duration of response(Time from measurement criteria are first met for CR/PR to either the first time disease progression is documented or death (for not progressed patients who deceased within 60 days from last tumor assessment) until maximum 5 years after EOT)
- Safety/toxicity and tolerability profil: Severety of adverse events(until 14 days after End of Treatment)
- Safety/toxicity and tolerability profil: ECOG(until 14 days after End of Treatment)
- Safety/toxicity and tolerability profil: Laboratory assessments(until 14 days after End of Treatment)
- Safety/toxicity and tolerability profil: review of body systems(until 14 days after End of Treatment)
- Progression Free Survival and sensitivity analysis: Effect of previous chemotherapy on prognostic factors(From date of first study treatment administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years after End of Treatment)
- Progression Free Survival and sensitivity analysis: effect of ECOG on prognostic factors(From date of first study treatment administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years after End of Treatment)
- Progression Free Survival and sensitivity analysis: Effect of Center on prognostic factors(From date of first study treatment administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years after End of Treatment.)
- Progression Free Survival and sensitivity analysis: Effect of tumor location on prognostic factors(From date of first study treatment administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years after End of Treatment)
- Objective tumor response: Rate of complete response and partial response(performed within 28 days before start therapy, 3 times every 6 weeks and afterwards every 8 weeks)
- Duration of overall survival(Time from Day 1 of therapy to death until maximum 5 years after End of Treatment)