A Multicenter, Randomized, Open-lable, Parallel-controlled, Phase II Study to Evaluate the Differences of Safety and Efficacy of Irinotecan Liposome Injection-containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma
Overview
- Phase
- Phase 2
- Intervention
- Irinotecan Liposome Injection
- Conditions
- Pancreatic Cancer Non-resectable
- Sponsor
- CSPC Ouyi Pharmaceutical Co., Ltd.
- Enrollment
- 153
- Primary Endpoint
- Progression-Free Survival (PFS)
- Status
- Not yet recruiting
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a multicenter, randomized, open-lable, parallel-controlled phase II study of irinotecan liposome injection-containing regimens versus nab-paclitaxel plus gemcitabine in patients with previously untreated, metastatic pancreatic adenocarcinoma. The purpose of this study is to evaluate the differences of safety and efficacy of irinotecan liposome injection-containing regimens versus nab-paclitaxel plus gemcitabine in patients with previously untreated, metastatic pancreatic adenocarcinoma.
Detailed Description
This is a multicentre randomized, open-label, parallel-controlled, phase II study to evaluate the efficacy and safety of irinotecan liposome injection-containing regimens. Eligible patients will be randomly divided into two cohorts at a ratio of 2:1. The patients in cohort 1 (the experimental group) will receive irinotecan liposome injection combined with 5-fluorouracil (5-FU), leucovorin (LV) and oxaliplatin.The patients in cohort 2 (the control group) will receive nab-paclitaxel plus gemcitabine.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 18 to 70 years old (inclusive), regardless of gender;
- •Histologically or cytologically confirmed unresectable, locally advanced, or metastatic pancreatic adenocarcinoma;
- •At least one measurable lesion according to RECIST 1.
- •No prior systemic anti-tumor therapy, except those with disease progression more than 6 months after adjuvant therapy or neoadjuvant therapy;
- •Patients with prior local treatment (radical radiotherapy or radical chemoradiotherapy, etc.) may be enrolled provided that the local treatment does not involve the target lesion, or the target lesion is within the treatment area, but the size has increased more than 20% since the post-treatment evaluation, and also must be completed at least 4 weeks before the first administration of the study drug, palliative decompensated radiotherapy (such as bone metastases) must be completed at least 2 weeks before the first administration of the study drug;
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1;
- •Life expectancy \>3 months;
- •Adverse reactions must recover to grade 1 or baseline according to CTCAE 5.0 (except for toxicity such as alopecia, grade 2 or less sensory neuropathy, etc., which have been judged no safety risk by investigators).
- •Patients should not receive cell growth factors or blood and platelet transfusion within 7 days before the initiate administration of study drug, and laboratory test must meet the following criteria:
- •neutrophile count ≥1.5×10\^9/L; platelet count ≥100×10\^9/L; hemoglobin ≥90 g/L or ≥5.6 mmol/L; serum creatinine ≤1×ULN or creatinine clearance rate must be ≥ 50 mL/min when serum creatinine \>1.0×ULN; total bilirubin ≤1.5×ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN or ≤5×ULN if intrahepatic lesions exist; Albumin ≥3 g/dL.
Exclusion Criteria
- •Patients with acinar cell carcinoma, pancreatoblastoma, solid pseudopapillary tumor and pancreatic neuroendocrine tumor;
- •Patients with definitive diagnosis of CNS metastasis;
- •Patients with hepatic encephalopathy at screening;
- •Patients with clinically symptomatic ascites requiring puncture or drainage or who have received ascites drainage within the past 3 months, except for those with only a small amount of ascites on imaging but no clinical symptoms;
- •Uncontrolled third lacunar effusion other than ascites (e.g., large pleural or pericardial effusion) within 4 weeks before the first administration of the test drug;
- •Previous malignancies in the past five years (except radically resected and non-recurring basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder carcinoma, local prostate carcinoma, carcinoma in situ of cervical, or other carcinoma in situ);
- •Patients with partial or complete biliary obstruction who has not relieved by active treatment;
- •History of serious cardiovascular disease, including but not limited to:
- •Acute myocardial infarction, unstable angina pectoris, coronary angioplasty, stroke, severe pulmonary embolism; 2) New York Heart Association class grade III or IV congestive heart failure or left ventricular ejection fraction (LVEF) \< 50%; 3) Poorly controlled hypertension (systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure≥ 95 mmHg) with optimal treatment; 4) Ventricular arrhythmia; 5) Patients with prolonged QT/QTc interval in baseline electrocardiogram (ECG) (QTcF \> 480 ms, Fridericia formula: QTcF = QT/(RR\^0.33), RR = 60/heart rate); 6) Patients with clinically significant abnormal electrocardiogram (ECG) according to the investigator's assessment.
- •9.Patients with uncontrolled active bleeding.
Arms & Interventions
Cohort 1: Irinotecan Liposome Injection + 5-FU/LV + Oxaliplatin
The patients in cohort 1 will receive irinotecan liposome injection combined with 5-fluorouracil (5-FU), leucovorin(LV) and oxaliplatin intravenously on day 1 and day 15 of every 28-day cycle until disease progression or unacceptable toxicity, or termination of the study due to other reasons.
Intervention: Irinotecan Liposome Injection
Cohort 1: Irinotecan Liposome Injection + 5-FU/LV + Oxaliplatin
The patients in cohort 1 will receive irinotecan liposome injection combined with 5-fluorouracil (5-FU), leucovorin(LV) and oxaliplatin intravenously on day 1 and day 15 of every 28-day cycle until disease progression or unacceptable toxicity, or termination of the study due to other reasons.
Intervention: Fluorouracil
Cohort 1: Irinotecan Liposome Injection + 5-FU/LV + Oxaliplatin
The patients in cohort 1 will receive irinotecan liposome injection combined with 5-fluorouracil (5-FU), leucovorin(LV) and oxaliplatin intravenously on day 1 and day 15 of every 28-day cycle until disease progression or unacceptable toxicity, or termination of the study due to other reasons.
Intervention: Leucovorin
Cohort 1: Irinotecan Liposome Injection + 5-FU/LV + Oxaliplatin
The patients in cohort 1 will receive irinotecan liposome injection combined with 5-fluorouracil (5-FU), leucovorin(LV) and oxaliplatin intravenously on day 1 and day 15 of every 28-day cycle until disease progression or unacceptable toxicity, or termination of the study due to other reasons.
Intervention: Oxaliplatin
Cohort 2: Nab-paclitaxel + Gemcitabine
The patients in cohort 2 will receive nab-paclitaxel and gemcitabine intravenously on day 1、day 8 and day 15 of every 28-day cycle until disease progression or unacceptable toxicity, or termination of the study due to other reasons.
Intervention: Nab paclitaxel
Cohort 2: Nab-paclitaxel + Gemcitabine
The patients in cohort 2 will receive nab-paclitaxel and gemcitabine intravenously on day 1、day 8 and day 15 of every 28-day cycle until disease progression or unacceptable toxicity, or termination of the study due to other reasons.
Intervention: Gemcitabine
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: Up to twelve months after the last patient's first administration
Time from date of the first dose to date of recorded disease progression or death, whichever occurs first.
Secondary Outcomes
- Duration of Response (DOR)(Up to twelve months after the last patient's first administration)
- Incidence of treatment-related adverse events (AEs) and serious adverse events (SAEs)(Up to twelve months after the last patient's first administration)
- UGT1A1(Within 3 days before the first dose)
- Objective Response Rate (ORR)(Up to twelve months after the last patient's first administration)
- Overall survival (OS)(Up to twelve months after the last patient's first administration)
- Disease Control Rate (DCR)(Up to twelve months after the last patient's first administration)
- Peak Plasma Concentration(Day 0 to Day 7 of circle 1)
- Area under the plasma concentration versus time curve(Day 0 to Day 7 of circle 1)