The aim of our study is to evaluate the efficacy and safety of NALIRI plus 5FU versus paclitaxel as a second-line therapy in patients with locally advanced or metastatic ESCC who had failed to cisplatin- or oxaliplatin-based first-line chemotherapy. The hypotheses are as follows: H0: the percentage of patients alive at 9 months of 40% is not useful. H1: the percentage of patients alive at 9 months of 60% is expected.
Principal objective: • To evaluate the survival of patients at 9 months Secondary objectives: * Progression-free survival (PFS) (clinical and/or radiological) * Overall survival (OS) * Best response rate during treatment according to RECIST 1.1 criteria (according to the investigator and the centralised review committee) * Toxicity (NCI CTC 4.0) * Quality of life (QLQ-C30 and OES18 questionnaires of the EORTC) Arm A (experimental arm): Nal IRI plus LV5-FU (D1=D28) Nal-IRI: 70 mg/m² intravenous over 90 minutes Followed by intravenous folinic acid 400 mg/m² over 30 minutes or L-folinic acid: 200 mg/m² over 30 minutes And then 5-FU 2,400 mg/m² over 46 hours on D1 to D14 Arm B (control arm): PACLITAXEL (D1=D28) Paclitaxel: 80 mg/m² at D1, D8 and D15 Patients will be randomized in a 1:1 ratio using the minimisation technique. Randomisation will be stratified based on the following factors: * Centre * WHO performance status: 0/1 versus 2 An analysis of circulating tumour DNA (using genetic mutations, in particular, TP53, and DNA methylation analyses) will be performed before the 1st cycle of treatment and at D28, in order to look for factors predictive of response to treatment (decrease in unbound DNA).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
106
onivyde will be administered first, followed by folinic acid or L-folinic acid and then 5-FU at D1 and D14.
Paclitaxel : 80 mg/m2 IV during 60 minutes at D1, D8 and D15
Chu Amiens
Amiens, France
Institut Sainte Catherine
Avignon, France
Hopital Européen
Marseille, France
Ch Le Raincy
Montfermeil, France
survival at 9 months
The principal objective is to evaluate survival at 9 months in patients presenting with metastatic oesophageal squamous cell carcinoma (OSC) treated with Nal-IRI/LV5-FU or with paclitaxel.
Time frame: 9 months
Progression-free survival
Clinical Progression-free survival and/or radiological Progression free survival will be evaluated
Time frame: 5 years
Overall survival (OS)
evaluate the overall survival
Time frame: 1 year
Best response rate during treatment
Best response rate during treatment according to RECIST 1.1 criteria (according to the investigator and with centralised review)
Time frame: 6 months
Toxicity (NCI-CTC v4)
all observed toxicities, graded according to NCI-CTC v4 and the SAE
Time frame: 6 months
Quality of life (questionnaires)
Quality of life (QLQ-C30 questionnaires of EORTC) and OES18 questionnaires of EORTC
Time frame: 6 months
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Chu Saint Louis
Paris, France
Ch Perpignan
Perpignan, France
Chu de Poitiers
Poitiers, France
Chu Rouen
Rouen, France
Ch Duchenne
St-Malo, France