Randomized phase II study comparing 5FU/LV+Nal-IRI, gemcitabine+Nab-paclitaxel or a sequential regimen of 2 months 5FU/LV+Nal-IRI followed by two months of gemcitabine+Nab-paclitaxel, in metastatic pancreatic cancer

Phase 2/3

Not yet recruiting

• Conditions: Metastatic pancreatic cancer

• Registration Number: 2024-518143-38-00
• Lead Sponsor: Fondation Franc.Cancerologie Digestive

Brief Summary

- Compare the progression free survival at 6 months in experimental arms (arm A: Nal-Iri plus 5FU/LV and Nab-Paclitaxel plus Gemcitabine alternatively, arm B: Nal-Iri plus 5FU/LV) VS the reference arm (arm C: Nab-Paclitaxel plus Gemcitabine) according to the RECIST 1.1 criteria

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-10-25
• Last Update Posted: 2024-10-25

Recruitment & Eligibility

• Status: Authorised, recruitment pending
• Sex: Not specified
• Target Recruitment: 288

Inclusion Criteria

• Histopathologically or cytologically proven pancreatic adenocarcinoma (on primitive or metastatic lesion)

• 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 7 months following the last dose of study drug.

• Patient affiliated to social security - Regular follow-up possible

• 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)

Exclusion Criteria

• Uncontrolled brain or meningeal metastasis, or bone metastasis (no need of systematic CT scan)

• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure.

• Known hypersensitivity to any of the drugs /constituents or non-lipososomal 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

• Partial or complete DPD deficiency (Uracilemia ≥ 16 ng/ml)

• Pregnant or breast feeding

• 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary endpoint is the rate of patients alive without progression at 6 months after inclusion		The primary endpoint is the rate of patients alive without progression at 6 months after inclusion

Secondary Outcome Measures

Name	Time	Method
Best Objective Response (BOR): BOR is defined as complete or partial response rate according to scans and RECIST v1.1 criteria over the entire treatment period.		Best Objective Response (BOR): BOR is defined as complete or partial response rate according to scans and RECIST v1.1 criteria over the entire treatment period.
Progression free survival (PFS): 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).		Progression free survival (PFS): 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).
Overall survival (OS): OS is defined as the time between the date of randomization and the date of death (whatever the cause).		Overall survival (OS): OS is defined as the time between the date of randomization and the date of death (whatever the cause).
Depth of response: This is defined as the relative difference between the sum of the largest diameters of target lesions in the NADIR (in the absence of new lesions or progression of non-target lesions) and the sum of the largest diameters of the target lesions at inclusion.		Depth of response: This is defined as the relative difference between the sum of the largest diameters of target lesions in the NADIR (in the absence of new lesions or progression of non-target lesions) and the sum of the largest diameters of the target lesions at inclusion.
Early tumor shrinkage: This is defined as the relative difference between the sum of the largest diameters of target lesions at 8 weeks and this sum at inclusion. Early decrease corresponds to a relative difference of > 20% in RECIST v1.1.		Early tumor shrinkage: This is defined as the relative difference between the sum of the largest diameters of target lesions at 8 weeks and this sum at inclusion. Early decrease corresponds to a relative difference of > 20% in RECIST v1.1.
Time to treatment failure is defined as the time between the date of randomization and the date of discontinuation of all protocol treatments (regardless of cause) or date last news for patients alive under treatment.		Time to treatment failure is defined as the time between the date of randomization and the date of discontinuation of all protocol treatments (regardless of cause) or date last news for patients alive under treatment.
Safety: Toxicities are evaluated according to NCI-CTC v4.0.		Safety: Toxicities are evaluated according to NCI-CTC v4.0.
Quality of life (EORTC QLQ-C30): Quality of life will be assessed according to the questionnaire of EORTC QLQ-C30		Quality of life (EORTC QLQ-C30): Quality of life will be assessed according to the questionnaire of EORTC QLQ-C30
Evolution of tumoral markers: The evolution of the markers will be analysed by a graphical representation at each time points of the percentage change from baseline.		Evolution of tumoral markers: The evolution of the markers will be analysed by a graphical representation at each time points of the percentage change from baseline.

Trial Locations

Locations (1)

Hopital Europeen Georges Pompidou; 🇫🇷 Paris, France

Hopital Europeen Georges Pompidou

🇫🇷Paris, France

Julien TAIEB

Site contact

+33156093551

julien.taieb@aphp.fr