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

NCT05472259 | Recruiting Phase 2 DMC

• 1 other identifier: NALPAC
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 13

Brief Summary

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

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Efficacy of NALIRINOX and NALIRI through Progression-Free Survival at D85

  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.

  at day 85 from randomization

Secondary Outcomes (12)

• Safety/toxicity and tolerability profil: Severety of adverse events

  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: ECOG

  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 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.

Other Outcomes (1)

• Exploratory lab investigation for potential prognostic and predictive biomarkers on blood and tumor samples

  Sapmples will be collected throughout the study and shipped to the sponsor maximum 1 year after last 15 day follow-up visit

Study Arms (2)

Arm A NALIRI

ACTIVE COMPARATOR

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.

Drug: Nanoliposomal irinotecan; Drug: 5 FU; Drug: Leucovorin

Arm B NALIRINOX

EXPERIMENTAL

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.

Drug: Nanoliposomal irinotecan; Drug: 5 FU; Drug: Leucovorin; Drug: Oxaliplatin

Interventions

Nanoliposomal irinotecan DRUG

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

Also known as: Onyvide

Arm A NALIRI; Arm B NALIRINOX

5 FU DRUG

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

Also known as: Fluorouracil

Arm A NALIRI; Arm B NALIRINOX

Leucovorin DRUG

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

Also known as: Folinate, Elvorine

Arm A NALIRI; Arm B NALIRINOX

Oxaliplatin DRUG

Only administered in the investigational arm (Nalirinox): a dose of 60 mg/m² is administered in combination with nanoliposomal irinotecan, 5FU and Leucovorin

Arm B NALIRINOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Belgian Group of Digestive Oncology: lead
• University Hospital St Luc, Brussels: collaborator

Study Sites (13)

UZ Antwerpen

Antwerp, Antwerp, 2650, Belgium

RECRUITING

ULB Erasme

Brussels, Brussels Capital, 1070, Belgium

RECRUITING

Cliniques Universitaires Saint-Luc UCL

Brussels, Brussels Capital, 1200, Belgium

RECRUITING

CHC MontLégia

Liège, Liège, 4000, Belgium

RECRUITING

AZ St-Lucas

Bruges, West-Vlaanderen, Belgium

NOT YET RECRUITING

AZ Imelda

Bonheiden, Belgium

RECRUITING

Grand Hopital de Charleroi

Charleroi, Belgium

RECRUITING

AZ Maria Middelares

Ghent, Belgium

RECRUITING

University Hospital Ghent

Ghent, Belgium

RECRUITING

Pôle Hospitalier Jolimont (HELORA)

Haine-Saint-Paul, 7100, Belgium

RECRUITING

CHU Ambroise Paré

Mons, Belgium

RECRUITING

CHR Namur

Namur, Belgium

RECRUITING

AZ Turnhout

Turnhout, 2300, Belgium

RECRUITING

MeSH Terms

Interventions

irinotecan sucrosofate; Fluorouracil; Leucovorin; Oxaliplatin

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Ivan Borbath

  University hospital St-luc, Brussel

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lina Dewever

CONTACT

+32 (0) 479 36 63 82; lina.dewever@bgdo.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2021
• First Posted: July 25, 2022
• Study Start: May 25, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 6, 2025

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (13)