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

• Status: Recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Federation Francophone de Cancerologie Digestive
• Treatments: Albumin-Bound Paclitaxel; Fluorouracil; Gemcitabine; Irinotecan; Paclitaxel

Criteria

Inclusion Criteria:

• 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

• 18 ≤ age ≤ 75 years

• Life expectancy >12 weeks

• Performance status WHO < 2

• No prior chemotherapy : adjuvant chemotherapy by gemcitabine +/- capecitabine is allowed if ended at least 12 months before the inclusion and adjuvant or neo-adjuvant FOLRIFINOX chemotherapy is allowed if ended at least 12 months prior the inclusion

• Pain well controlled before the inclusion of the patient

• 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.

• Patient affiliated to social security

• Regular follow-up possible

Exclusion Criteria:

• 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.

• Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before inclusion.

• 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

• Pregnant or breast feeding