A Study Evaluating the Efficacy of 5-FU + NALIRI and 5-FU + NALIRINOX for PDAC (NALPAC)

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

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

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)

Inclusion Criteria:

• Histologically proven metastatic adenocarcinoma of the pancreas
• Progression documented after gemcitabine-Abraxane, or gemcitabine monotherapy
• Signed written informed consent
• Age ≥ 18
• 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

Exclusion Criteria:

• 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