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

NCT ID: NCT05472259

Last Updated: 2025-02-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

134 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-25

Study Completion Date

2027-12-31

Brief Summary

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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

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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)

Conditions

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Metastatic Pancreatic Ductal Adenocarcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Nanoliposomal irinotecan

Intervention Type 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

5 FU

Intervention Type 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

Leucovorin

Intervention Type 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

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.

Group Type EXPERIMENTAL

Nanoliposomal irinotecan

Intervention Type 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

5 FU

Intervention Type 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

Leucovorin

Intervention Type 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

Oxaliplatin

Intervention Type DRUG

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

Interventions

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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

Intervention Type 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

Intervention Type 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

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

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Onyvide Fluorouracil Folinate Elvorine

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital St Luc, Brussels

OTHER

Sponsor Role collaborator

Belgian Group of Digestive Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ivan Borbath

Role: PRINCIPAL_INVESTIGATOR

University hospital St-luc, Brussel

Locations

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UZ Antwerpen

Antwerp, Antwerp, Belgium

Site Status RECRUITING

ULB Erasme

Brussels, Brussels Capital, Belgium

Site Status RECRUITING

Cliniques Universitaires Saint-Luc UCL

Brussels, Brussels Capital, Belgium

Site Status RECRUITING

CHC MontLégia

Liège, Liège, Belgium

Site Status RECRUITING

AZ St-Lucas

Bruges, West-Vlaanderen, Belgium

Site Status NOT_YET_RECRUITING

AZ Imelda

Bonheiden, , Belgium

Site Status RECRUITING

Grand Hopital de Charleroi

Charleroi, , Belgium

Site Status RECRUITING

AZ Maria Middelares

Ghent, , Belgium

Site Status RECRUITING

University Hospital Ghent

Ghent, , Belgium

Site Status RECRUITING

Pôle Hospitalier Jolimont (HELORA)

Haine-Saint-Paul, , Belgium

Site Status RECRUITING

CHU Ambroise Paré

Mons, , Belgium

Site Status RECRUITING

CHR Namur

Namur, , Belgium

Site Status RECRUITING

AZ Turnhout

Turnhout, , Belgium

Site Status RECRUITING

Countries

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Belgium

Central Contacts

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Lina Dewever

Role: CONTACT

+32 (0) 479 36 63 82

Facility Contacts

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Sanne Wouters

Role: primary

Axelle Ghilain

Role: primary

Tuan Le

Role: primary

Jocelyne Gilson

Role: primary

Tania Maerten

Role: primary

Doreen Iwens

Role: primary

Matthias Papier

Role: primary

Margaux Vansteelant

Role: primary

Tine Derre

Role: primary

Isabelle Buelens

Role: primary

064/234662

Mariane Blockmans

Role: primary

Christine Leon

Role: primary

Nel Bovin

Role: primary

0032 14406912

Other Identifiers

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NALPAC

Identifier Type: -

Identifier Source: org_study_id

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