Clinical trial NCT05472259: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Pancreatic Ductal Adenocarcinoma
Lead sponsor: Belgian Group of Digestive Oncology
Sponsor class: OTHER
Collaborators: name: University Hospital St Luc, Brussels
First posted: 2022-07-25
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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)

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

Primary outcomes:
measure: Efficacy of NALIRINOX and NALIRI through Progression-Free Survival at D85
timeFrame: at day 85 from randomization
Secondary outcomes:
measure: Safety/toxicity and tolerability profil: Severety of adverse events
timeFrame: until 14 days after End of Treatment
measure: Safety/toxicity and tolerability profil: Laboratory assessments
timeFrame: until 14 days after End of Treatment
measure: Safety/toxicity and tolerability profil: ECOG
timeFrame: until 14 days after End of Treatment
measure: Safety/toxicity and tolerability profil: review of body systems
timeFrame: until 14 days after End of Treatment
measure: Progression Free Survival and sensitivity analysis: Effect of Center on prognostic factors
timeFrame: 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.
measure: Progression Free Survival and sensitivity analysis: Effect of tumor location on prognostic factors
timeFrame: 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
measure: Progression Free Survival and sensitivity analysis: Effect of previous chemotherapy on prognostic factors
timeFrame: 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
measure: Progression Free Survival and sensitivity analysis: effect of ECOG on prognostic factors
timeFrame: 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
measure: Objective tumor response: Rate of complete response and partial response
timeFrame: performed within 28 days before start therapy, 3 times every 6 weeks and afterwards every 8 weeks
measure: Duration of overall survival
timeFrame: Time from Day 1 of therapy to death until maximum 5 years after End of Treatment
measure: Duration of disease control
timeFrame: 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
measure: Duration of response
timeFrame: 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
Other outcomes:
measure: Exploratory lab investigation for potential prognostic and predictive biomarkers on blood and tumor samples
timeFrame: Sapmples will be collected throughout the study and shipped to the sponsor maximum 1 year after last 15 day follow-up visit
Locations:
city: Brugge
country: Belgium
facility: AZ St-Lucas
state: West-Vlaanderen
city: Antwerp
country: Belgium
facility: UZ Antwerpen
city: Bonheiden
country: Belgium
facility: AZ Imelda
city: Brussels
country: Belgium
facility: ULB Erasme
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc UCL
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi
city: Ghent
country: Belgium
facility: AZ Maria Middelares
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Haine-Saint-Paul
country: Belgium
facility: Pôle Hospitalier Jolimont (HELORA)
city: Liège
country: Belgium
facility: CHC MontLégia
city: Mons
country: Belgium
facility: CHU Ambroise Paré
city: Namur
country: Belgium
facility: CHR Namur
city: Turnhout
country: Belgium
facility: AZ Turnhout
Study officials:
affiliation: University hospital St-luc, Brussel
name: Ivan Borbath
role: PRINCIPAL_INVESTIGATOR
References: