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

NCT03719924 | Completed Phase 2

• 1 other identifier: PRODIGE 62 - OESIRI
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Squamous Cell Carcinoma

Keywords

ESCC NAL-IRI

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Progression-free survival

  5 years

• Overall survival (OS)

  1 year

• Best response rate during treatment

  6 months

• Toxicity (NCI-CTC v4)

  6 months

• Quality of life (questionnaires)

  6 months

Study Arms (2)

arm A: ONIVYDE

EXPERIMENTAL

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

Arm B: TAXOL

ACTIVE COMPARATOR

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

Interventions

Onivyde DRUG

onivyde will be administered first, followed by folinic acid or L-folinic acid and then 5-FU at D1 and D14.

Also known as: no other intervention name to add

arm A: ONIVYDE

Paclitaxel DRUG

Paclitaxel : 80 mg/m2 IV during 60 minutes at D1, D8 and D15

Also known as: no other intervention name to add

Arm B: TAXOL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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, 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.

You may not qualify if:

• 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).
• 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

Sponsors & Collaborators

• Federation Francophone de Cancerologie Digestive: lead
• Shire: collaborator
• Servier: collaborator

Study Sites (9)

Chu Amiens

Amiens, France

Location

Institut Sainte Catherine

Avignon, France

Location

Hopital Européen

Marseille, France

Location

Ch Le Raincy

Montfermeil, France

Location

Chu Saint Louis

Paris, France

Location

Ch Perpignan

Perpignan, France

Location

Chu de Poitiers

Poitiers, France

Location

Chu Rouen

Rouen, France

Location

Ch Duchenne

St-Malo, France

Location

Related Publications (2)

• 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.

  PMID: 31899122 BACKGROUND

• Tougeron D, Mineur L, Zaanan A, Kadi M, Poisson Ligeza C, Bourgeois V, Martin-Babau J, Fadin A, Jestin le Tallec V, Ly Lebrun V, Dubreuil O, Khemissa Akouz F, Thimonier E, Bouche O, Lievre A, Di Fiore F, Lecomte T, Lepage C, Hautefeuille V; PRODIGE 62-FFCD 1701-OESIRI investigators/collaborators. Nal-IRI/LV5-FU versus paclitaxel as second-line therapy in patients with metastatic esophageal squamous cell carcinoma (PRODIGE 62-FFCD 1701-OESIRI). Eur J Cancer. 2025 Oct 1;228:115741. doi: 10.1016/j.ejca.2025.115741. Epub 2025 Aug 22.

  PMID: 40876084 DERIVED

MeSH Terms

Conditions

Carcinoma, Squamous Cell

Interventions

irinotecan sucrosofate; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• DAVID TOUGERON

  PRODIGE 62 - FFCD 1701

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All initial characteristics will be described in the overall population and by treatment arm. Evaluation criteria related to efficacy and safety will be described by treatment arm. Initial characteristics of best response and toxicities will be evaluated using usual statistics: for quantitative variables: mean, standard deviation, median, interquartile interval and range and for qualitative variables: frequencies and percentages. For the primary evaluation end point, a one-sided 95% confidence interval (CI) will be calculated in the experimental arm.

Study Record Dates

• First Submitted: September 26, 2018
• First Posted: October 25, 2018
• Study Start: March 7, 2019
• Primary Completion: April 15, 2024
• Study Completion: September 29, 2024
• Last Updated: January 8, 2025

Record last verified: 2025-01

Locations

FR (9)