First Line Metastatic Pancreatic Cancer : 5FU/LV+Nal-IRI, Gemcitabine+Nab-paclitaxel or a Sequential Regimen of 2 Months 5FU/LV+Nal-IRI

NCT03693677 | Completed Phase 2

• 3 other identifiers: PRODIGE 61 - FUNGEMAXFFCD 17022017-004309-41
• Study Type: interventional
• Target: 288
• Locations: 2 countries
• Sites: 36

Brief Summary

In Europe, pancreatic cancer (PC) is the 7th most common cancer and the 5th leading cause of cancer death in Europe. Each year, the number of deaths due to prostate cancer is almost as high as the number of new cases diagnosed reflecting the poor prognosis associated with this disease. PC is insidious and is often diagnosed late. Despite advances in the management of other more common gastrointestinal cancers, the treatment of PC has had few benefits inherent in recent advances in digestive oncology. Gemcitabine has thus remained the reference treatment for more than 10 years. Recent studies have shown that gemcitabine/Nab-paclitaxel combination therapy is more effective in PC than gemcitabine-based therapy alone. In addition, multidrug therapy approaches (Irinotecan-5FU/LV) have also emerged to avoid the emergence of resistance to treatments while limiting toxicities. The recently developed Nal-IRI has also shown interesting efficacy in patients with metastatic PC previously treated with gemcitabine, with improved overall survival median and limited toxicity. Based on this information, the NAPOLI trial was conducted in patients with second line PC comparing the efficacy of Nal-IRI/5FU/LV or Nal-IRI and 5FU/LV alone; in this key study, the combination Nal-IRI/5FU/LV treatment was more effective than monotherapies (Nal-IRI or 5FU/LV alone). Based on all these data, a Phase II trial testing the standard of care gemcitabine/nab-paclitaxel vs Nal-IRI/5FU/LV vs Nal-IRI/5FU/LV 2-months sequential regimen followed by gemcitabine/nab-paclitaxel will be performed. This will allow us to i) know the tolerance and efficacy of Nal-IRI/5FU/LV in the first line of treatment, ii) test a new sequential strategy with Nal-IRI but also iii) compare our results in the experimental arms with one of the two world standard therapeutic regimens: gemcitabine + nab-Paclitaxel. All this in order to improve the management of patients with PC from the first line of treatment.

Conditions

Metastatic Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• The progression free survival at 6 months according to the RECIST 1.1 criteria

  PFS is defined as the time between the date of randomization and the date of the first radiological and/or clinical progression or the date of death (for whatever reason). Patients living without progression will be censured at date of last news. Progression is assessed by investigator and central review according to RECIST v1.1 criteria.

  6 months

Secondary Outcomes (5)

• Progression free survival at 6 months (according to central review)

  6 months

• Best objective response rate

  An average of 1 year

• Overall survival

  2 years

• Time to treatment failure

  An average of 1 year

• Treatment safety

  An average of 1 year

Study Arms (3)

Nal-IRI/5-FU/LV + Nab-paclitaxel/Gemcitabine alternatively

EXPERIMENTAL

Nal-IRI plus 5-FU/LV and Nab-Paclitaxel plus Gemcitabine alternately every two months * Nal-IRI at 80 mg/m2 IV over 90 minutes followed by folinic acid (leucovorin 400 mg/m2 IV, or Elvorin 200 mg/m2 IV over 30 minutes) then by 5-FU 2400 mg/m2 IV over 46-hours, every 2 weeks. * Nab-Paclitaxel + Gemcitabine (6 injections, one injection three weeks out of four; so ≈ 2 months per cycle) Day 1 (D1): Nab-Paclitaxel plus Gemcitabine at the dose of : * Gemcitabine: 1000 mg/m² in 500 ml normal saline infusion at a fixed dose rate of 10 mg/m²/min (i.e. 100 min). * Nab-Paclitaxel: 125 mg/m2 This treatment is administered at D1, D8, D15 and at D29, D36, D43.

Drug: Irinotecan Liposomal Injection; Drug: 5-FU/LV; Drug: Nab-Paclitaxel; Drug: Gemcitabine

Nal-IRI/5-FU/LV

EXPERIMENTAL

Nal-IRI plus 5-FU/LV Nal-IRI at 80 mg/m2 IV over 90 minutes followed by folinic acid (leucovorin 400 mg/m2 IV, or Elvorin 200 mg/m2 IV over 30 minutes) then by 5-FU 2400 mg/m2 IV over 46-hours, every 2 weeks.

Drug: Irinotecan Liposomal Injection; Drug: 5-FU/LV

Nab-paclitaxel/Gemcitabine

ACTIVE COMPARATOR

Nab-Paclitaxel plus Gemcitabine Nab-Paclitaxel + Gemcitabine (6 courses, one course three weeks out of four; so ≈ 2 months per cycle) Day 1 (D1): Nab-Paclitaxel + Gemcitabine at the dose of : * Gemcitabine: 1000 mg/m² in 500 ml normal saline infusion at a fixed dose rate of 10 mg/m²/min (i.e. 100 min). * Nab-Paclitaxel: 125 mg/m2 This treatment is administered at D1, D8, D15 and at D29, D36, D43.

Drug: Nab-Paclitaxel; Drug: Gemcitabine

Interventions

Irinotecan Liposomal Injection DRUG

Nal-IRI at 80 mg/m2 IV over 90 minutes

Also known as: Nal-IRI

Nal-IRI/5-FU/LV; Nal-IRI/5-FU/LV + Nab-paclitaxel/Gemcitabine alternatively

5-FU/LV DRUG

5-FU 2400 mg/m2 IV over 46-hours, every 2 weeks.

Nal-IRI/5-FU/LV; Nal-IRI/5-FU/LV + Nab-paclitaxel/Gemcitabine alternatively

Nab-Paclitaxel DRUG

Nab-Paclitaxel: 125 mg/m2 This treatment is administered at D1, D8, D15 and at D29, D36, D43.

Nab-paclitaxel/Gemcitabine; Nal-IRI/5-FU/LV + Nab-paclitaxel/Gemcitabine alternatively

Gemcitabine DRUG

1000 mg/m² in 500 ml normal saline infusion at a fixed dose rate of 10 mg/m²/min (i.e. 100 min). This treatment is administered at D1, D8, D15 and at D29, D36, D43.

Nab-paclitaxel/Gemcitabine; Nal-IRI/5-FU/LV + Nab-paclitaxel/Gemcitabine alternatively

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologically or cytologically proven pancreatic adenocarcinoma (on primitive or metastatic lesion)
• Metastatic disease at a distance
• At least one measurable lesion according RECIST v1.1 criteria
• ≤ age ≤ 75 years
• Life expectancy \>12 weeks
• Performance status WHO \< 2
• ANC ≥ 1,500 cells/μL (without the use of hematopoietic growth factors); platelet count ≥ 100,000 cells/μL, hemoglobin ≥ 9 g/dL (blood transfusions is permitted for patients with hemoglobin levels below 9 g/dL)
• Adequate hepatic function as evidenced by: Serum total bilirubin within normal range for the institution (Serum bilirubin ≤ 1,5 UNL) Biliary drainage allowed for biliary obstruction.
• Albumin levels ≥ 3.0 g/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN acceptable if liver metastases were present)
• Normal renal function test (creatinine clearance ≥ 50 ml/min)
• Normal ECG or ECG without any clinically significant findings
• Patient able to understand and sign an informed consent
• Females of child-bearing potential are required to test negative for pregnancy at the time of enrollment based on a urine or serum pregnancy test.
• Both male and female patients of reproductive potential were required to agree to use a reliable method of birth control, during the study and for 3 months following the last dose of study drug.

You may not qualify if:

• Uncontrolled brain or meningeal metastasis, or bone metastasis (no need of systematic CT scan)
• Prior radiation therapy (except if there is at least one measurable target outside irradiation area)
• Clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea \> Grade 1
• History of chronic inflammatory bowel disease
• Other types of pancreatic tumours, in particular endocrine or acinar cell tumours
• Ampulloma
• Gilbert's syndrome
• Presence of neuropathy \> grade 1 according to NCI-CTC
• History of any second malignancy in the last 5 years; subjects with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they had been continuously disease free for at least 5 years.
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure.
• Known hypersensitivity to any of the drugs /constituents or non-liposomal irinotecan
• Any other medical or social condition deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.
• Use of CYP3A4/UGT1A inducers/inhibitors
• Use of strong CYP2C8 inhibitors or inducers, or presence of any other contraindications for nab-paclitaxel or gemcitabine
• ILD presence

Sponsors & Collaborators

• Federation Francophone de Cancerologie Digestive: lead

Study Sites (36)

Clinique privée de l'Europe

Amiens, 80000, France

Location

CHU Hôtel Dieu

Angers, 49000, France

Location

Hôpital privé

Antony, 92160, France

Location

CH

Auxerre, 89000, France

Location

CH de la Côte Basque

Bayonne, 64100, France

Location

CHU Avicenne

Bobigny, 93022, France

Location

CH Duchenne

Boulogne-sur-Mer, 62200, France

Location

Hôpital Privé Sainte Marie

Chalon-sur-Saône, 71100, France

Location

CHU Estaing

Clermont-Ferrand, 63000, France

Location

Hopitaux civils de Colmar

Colmar, 68026, France

Location

CH Sud Francilien

Corbeil-Essonnes, 91100, France

Location

Centre GF Leclerc

Dijon, 21000, France

Location

CHU

Dijon, 21000, France

Location

Institut de cancérologie de Bourgogne

Dijon, 21000, France

Location

Hôpital Emile Roux

Le Puy-en-Velay, 43000, France

Location

CH Docteur Schaffner

Lens, 62218, France

Location

CHU Dupuytren

Limoges, 87000, France

Location

CH

Longjumeau, 91160, France

Location

Clinique privée Jean Mermoz

Lyon, 69000, France

Location

Hôpital Européen

Marseille, 13000, France

Location

Institut Paoli Calmettes

Marseille, 13000, France

Location

CH

Meaux, 77100, France

Location

CH

Niort, 79000, France

Location

Centre médical Oncogard

Nîmes, 30000, France

Location

CH Privé Sainte Marie

Osny, 95520, France

Location

Groupe Hospitalier La Pitié Salpêtrière

Paris, 75013, France

Location

Hôpital Cochin

Paris, 75679, France

Location

Hôpital Tenon

Paris, 75970, France

Location

Hopital Européen Georges Pompidou

Paris, France

Location

CH Saint Jean

Perpignan, 66000, France

Location

Centre Cario HPCA

Plérin, 22190, France

Location

CH Jacques Puel

Rodez, 12000, France

Location

CHU Charles Nicolle

Rouen, 76000, France

Location

CH Foch

Suresnes, 92150, France

Location

CHRU de Nancy

Vandœuvre-lès-Nancy, 54500, France

Location

CHU Clarac

Fort-de-France, 97200, Martinique

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

irinotecan sucrosofate; 130-nm albumin-bound paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Julien Taieb, Pr

  HEGP - Paris - France

  PRINCIPAL INVESTIGATOR

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: October 1, 2018
• First Posted: October 3, 2018
• Study Start: November 16, 2018
• Primary Completion: January 10, 2025
• Study Completion: January 10, 2025
• Last Updated: July 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1); FR (35)