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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03719924
Recruitment Status : Recruiting
First Posted : October 25, 2018
Last Update Posted : December 7, 2021
Information provided by (Responsible Party):
Federation Francophone de Cancerologie Digestive

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.

Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma Drug: Onivyde Drug: Paclitaxel Phase 2

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: 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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 106 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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.

Masking: None (Open Label)
Primary Purpose: Treatment
Actual Study Start Date : March 7, 2019
Estimated Primary Completion Date : July 15, 2023
Estimated Study Completion Date : April 15, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Paclitaxel

Arm Intervention/treatment
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: 80 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 Name: no other intervention name to add

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 Name: no other intervention name to add

Primary Outcome Measures :
  1. survival at 9 months [ Time Frame: 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.

Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: 5 years ]
    Clinical Progression-free survival and/or radiological Progression free survival will be evaluated

  2. Overall survival (OS) [ Time Frame: 1 year ]
    evaluate the overall survival

  3. Best response rate during treatment [ Time Frame: 6 months ]
    Best response rate during treatment according to RECIST 1.1 criteria (according to the investigator and with centralised review)

  4. Toxicity (NCI-CTC v4) [ Time Frame: 6 months ]
    all observed toxicities, graded according to NCI-CTC v4 and the SAE

  5. Quality of life (questionnaires) [ Time Frame: 6 months ]
    Quality of life (QLQ-C30 questionnaires of EORTC) and OES18 questionnaires of EORTC

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03719924

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Contact: DAVID TOUGERON ext 42109

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Chu Amiens Recruiting
Amiens, France
Institut Sainte Catherine Recruiting
Avignon, France
Contact: laurent mineur         
Hopital Européen Recruiting
Marseille, France
Contact: yves rinaldi         
Ch Le Raincy Recruiting
Montfermeil, France
Contact: IDA PAVESE         
Chu Saint Louis Recruiting
Paris, France
Contact: THOMAS APARICIO         
Ch Perpignan Recruiting
Perpignan, France
Chu de Poitiers Recruiting
Poitiers, France
Contact: DAVID TOUGERON, PR         
Chu Rouen Recruiting
Rouen, France
Contact: PIERRE MICHEL         
Ch Duchenne Recruiting
Saint-Malo, France
Contact: ROMAIN DESGRIPPES         
Sponsors and Collaborators
Federation Francophone de Cancerologie Digestive
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Principal Investigator: DAVID TOUGERON PRODIGE 62 - FFCD 1701
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Responsible Party: Federation Francophone de Cancerologie Digestive Identifier: NCT03719924    
Other Study ID Numbers: PRODIGE 62 - OESIRI
First Posted: October 25, 2018    Key Record Dates
Last Update Posted: December 7, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Federation Francophone de Cancerologie Digestive:
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Esophageal Squamous Cell Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action