Nal-iri/lv5-fu Versus Paclitaxel as Second Line Therapy in Patients With Metastatic Oesophageal Squamous Cell Carcinoma — OESIRI  

Squamous Cell Carcinoma Clinical Trial

Official title: Nal-IRI/LV5-FU VERSUS PACLITAXEL AS SECOND-LINE THERAPY IN PATIENTS WITH METASTATIC OESOPHAGEAL SQUAMOUS CELL CARCINOMA A Multi-centre, Randomized, Non-comparative Phase II Study

Status Active, not recruiting

Clinical Trial Summary

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.

Clinical Trial Description

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: 80 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 Patients known to be homozygous for the UGT1A1*28 allele who are to be randomized to the Nal-IRI/5-FU Arm receive the first cycle of therapy with a reduced dose of Nal IRI of 60 mg/m2. If the patient does not present any toxicity related to the medicinal product after the first administration of Nal IRI, the dose can be increased to 80 mg/m2 starting with cycle 2.

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). ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma
• Squamous Cell Carcinoma

• NCT number: NCT03719924
• Study type: Interventional
• Source: Federation Francophone de Cancerologie Digestive
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 7, 2019
• Completion date: April 15, 2025