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

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

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.

Study Overview

• Status: Completed
• Conditions: Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Onivyde; Drug: Paclitaxel

Detailed 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: 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
• Enrollment (Actual): 106
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Amiens, France
    • CHU Amiens
  • Avignon, France
    • Institut Sainte Catherine
  • Marseille, France
    • Hôpital Européen
  • Montfermeil, France
    • Ch Le Raincy
  • Paris, France
    • CHU Saint Louis
  • Perpignan, France
    • CH Perpignan
  • Poitiers, France
    • CHU de Poitiers
  • Rouen, France
    • CHU Rouen
  • Saint-Malo, France
    • Ch Duchenne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically proven metastatic oesophageal squamous cell carcinoma
• Patient in failure with 1st-line treatment with oxaliplatin or cisplatin. Patients presenting with resectable disease treated with surgery or neoadjuvant or adjuvant chemotherapy with oxaliplatin or cisplatin (with or without radiotherapy) can be included if a recurrence has occurred less than 6 months after the end of treatment
• Age ≥ 18 years
• Unresectable disease, measurable or not, according to RECIST 1.1 criteria
• WHO performance status ≤ 2
• Neutrophils ≥ 1500/mm3 (without use of haematopoietic growth factors), platelets ≥ 100 000/mm3, haemoglobin ≥ 9 g/dl (blood transfusions are authorised for patients with a haemoglobin less than 9 g/dl)
• Total bilirubin ≤ 2 x ULN (biliary drainage is authorised in case of a biliary obstruction); albumin ≥ 25 g/L; AST ≤ 2.5 x ULN, and ALT ≤ 2.5 x ULN (≤ 5 x ULN in case of hepatic metastases)
• Creatinine clearance ≥ 50 ml/min according to MDRD formula
• A normal ECG or ECG with no clinically significant findings
• Patient able to understand and to sign the informed consent form (or who has a legal guardian able to do so for him/him)
• Women of childbearing potential must have a negative pregnancy blood or urine test within 7 days prior to inclusion
• Women of childbearing potential, as well as men (who have sexual relations with women of childbearing potential) must agree to use an effective method of contraception throughout this study and during the 6 months following administration of the last dose of the study medicinal product
• Patient who is a beneficiary of the Social security system
• Patient for whom regular follow-up is possible.

Exclusion Criteria:

• Known brain or bone metastases
• Clinically significant gastrointestinal disorders, including hepatic, haemorrhagic, inflammatory, obstructive disorders or diarrhoea > grade 1
• History of chronic inflammatory bowel disease
• Gilbert's syndrome
• Interstitial lung disease
• Treatment with St John's Wort
• Medical history of Whipple procedure
• Body mass index < 18.5 kg/m2
• Combination with sorivudine and others analogues as brivudine (irreversibly inhibits the enzyme dihydropyrimidine dehydrogenase)
• History of progressive cancer or in remission of less than 3 years duration (patients who present with a cancer in situ or basal cell or squamous cell skin cancer during the last 3 years are eligible).
• Severe arterial thromboembolic events (myocardial infarction, unstable angina, stroke) less than 3 months before inclusion
• NYHA class III or IV congestive heart failure, ventricular arrhythmia or uncontrolled blood pressure
• Significant neuropathy ≥ grade 2 according to NCI CTCAE criteria (National Cancer Institute Common Terminology Criteria for Adverse Events) v.4.0.
• Known hypersensitivity or allergy to a component of the medicinal products used in the study.
• Known DPD deficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm B: TAXOL; TAXOL Premedication consists of corticosteroids, H1 antihistamines and H2 antagonists during 30 minutes at time 1 hour before chemotherapy One cycle every 28 days (D1=D28) 80 mg/m2 IV over 60 minutes at D1, D8 and D15	Drug: Paclitaxel; Paclitaxel : 80 mg/m2 IV during 60 minutes at D1, D8 and D15; Other Names: no other intervention name to add
Experimental: arm A: ONIVYDE; ONIVYDE ONIVYDE will be administered first, followed by folinic acid or L-folinic acid and then 5-FU at D1 and D14 ONIVYDE: 70 mg/m² intravenous over 90 minutes Folinic acid: 400 mg/m² intravenous over 30 minutes or L-folinic acid (racemic form L) 200 mg/m² over 30 minutes 5-FU: 2400 mg/m² over 46 hours	Drug: Onivyde; onivyde will be administered first, followed by folinic acid or L-folinic acid and then 5-FU at D1 and D14.; Other Names: no other intervention name to add

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Clinical Progression-free survival and/or radiological Progression free survival will be evaluated	5 years
Overall survival (OS)	evaluate the overall survival	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)	6 months
Toxicity (NCI-CTC v4)	all observed toxicities, graded according to NCI-CTC v4 and the SAE	6 months
Quality of life (questionnaires)	Quality of life (QLQ-C30 questionnaires of EORTC) and OES18 questionnaires of EORTC	6 months

Collaborators and Investigators

• Sponsor: Federation Francophone de Cancerologie Digestive
• Collaborators: Shire; Servier
• Investigators: Principal Investigator: DAVID TOUGERON, PRODIGE 62 - FFCD 1701

Publications and helpful links

General Publications

• Randrian V, Adenis A, Desrame J, Barbier E, Di Fiore F, Lievre A, Dahan L, Laurent-Puig P, Mineur L, Breysacher G, Roquin G, Louafi S, Lopez A, Louvet C, Borg C, Metges JP, Faroux R, Gaba L, Manfredi S, Tougeron D. Nal-IRI/LV5-FU versus paclitaxel as second-line therapy in patients with metastatic esophageal squamous cell carcinoma (OESIRI)-PRODIGE 62: A multicentre, randomised, non-comparative phase II study. Dig Liver Dis. 2020 Mar;52(3):347-350. doi: 10.1016/j.dld.2019.11.014. Epub 2019 Dec 30.

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2019
• Primary Completion (Actual): April 15, 2024
• Study Completion (Actual): September 29, 2024

Study Registration Dates

• First Submitted: September 26, 2018
• First Submitted That Met QC Criteria: October 24, 2018
• First Posted (Actual): October 25, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 7, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: ESCC NAL-IRI
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Carcinoma; Carcinoma, Squamous Cell; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: PRODIGE 62 - OESIRI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No