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

Official title

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

Overview

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

Detailed description

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)

Interventions

• Drug Nanoliposomal irinotecan
  In the control arm (Naliri) a dose of 70mg/m² is administered in combination with 5FU and leucovorin In the investigational arm (Nalirinox) a dose of 50mg/m² is administered in combination with 5FU, leucovorin and oxaliplatin
• Drug 5 FU
  In the control arm (Naliri) a dose of 2400 mg/m² is administered in combination with nanoliposomal irinotecan and leucovorin In the investigational arm (Nalirinox) a dose of 2400 mg/m² is administered in combination with nanoliposomal irinotecan, leucovorin and oxaliplatin
• Drug Leucovorin
  In the control arm (Naliri) a dose of 400 mg/m² is administered in combination with nanoliposomal irinotecan and 5FU In the investigational arm (Nalirinox) a dose of 400 mg/m² is administered in combination with nanoliposomal irinotecan, 5FU and oxaliplatin
• Drug Oxaliplatin
  Only administered in the investigational arm (Nalirinox): a dose of 60 mg/m² is administered in combination with nanoliposomal irinotecan, 5FU and Leucovorin

Primary outcome measures

• Efficacy of NALIRINOX and NALIRI through Progression-Free Survival at D85 [Time frame: at day 85 from randomization]

Secondary outcome measures (12)

• Safety/toxicity and tolerability profil: Severety of adverse events [Time frame: until 14 days after End of Treatment]
• Safety/toxicity and tolerability profil: Laboratory assessments [Time frame: until 14 days after End of Treatment]
• Safety/toxicity and tolerability profil: ECOG [Time frame: until 14 days after End of Treatment]
• Safety/toxicity and tolerability profil: review of body systems [Time frame: until 14 days after End of Treatment]
• Progression Free Survival and sensitivity analysis: Effect of Center on prognostic factors [Time frame: 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 [Time frame: 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 previous chemotherapy on prognostic factors [Time frame: 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 [Time frame: 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 [Time frame: performed within 28 days before start therapy, 3 times every 6 weeks and afterwards every 8 weeks]
• Duration of overall survival [Time frame: Time from Day 1 of therapy to death until maximum 5 years after End of Treatment]
• Duration of disease control [Time frame: 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 frame: 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]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Belgium · 13 centers

• UZ Antwerpen — Antwerp
• ULB Erasme — Brussels
• Cliniques Universitaires Saint-Luc UCL — Brussels
• CHC MontLégia — Liège
• AZ St-Lucas — Bruges
• AZ Imelda — Bonheiden
• Grand Hopital de Charleroi — Charleroi
• AZ Maria Middelares — Ghent
• … and 5 more centers

Identifiers

NCT: NCT05472259 · NALPAC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗