Squamous Cell CarcinomaPhase 2OESIRINCT03719924
Nal-iri/lv5-fu Versus Paclitaxel as Second Line Therapy in Patients With Metastatic Oesophageal Squamous Cell Carcinoma
A Phase 2 study testing Onivyde and Paclitaxel in people with Squamous Cell Carcinoma, run by Federation Francophone de Cancerologie Digestive at 9 sites in France.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma
- What is being tested?
- Onivyde and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 9 sitesFrance
- Study dates
- 7 Mar 2019to 29 Sep 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
France9 sites
Chu Amiens
Amiens
Institut Sainte Catherine
Avignon
Hopital Européen
Marseille
Ch Le Raincy
Montfermeil
Chu Saint Louis
Paris
Ch Perpignan
Perpignan
Chu de Poitiers
Poitiers
Chu Rouen
Rouen
Ch Duchenne
St-Malo
About this study
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
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.
Read the 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).
- Conditions
- Squamous Cell Carcinoma
- Being tested
- Onivyde, Paclitaxel
- Keywords
- ESCC NAL-IRI
- Medical subject headings
- Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OnivydeDrug
Also called no other intervention name to add
onivyde will be administered first, followed by folinic acid or L-folinic acid and then 5-FU at D1 and D14.
PaclitaxelDrug
Also called no other intervention name to add
Paclitaxel : 80 mg/m2 IV during 60 minutes at D1, D8 and D15
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 9 months
Secondary outcomes (5)
Progression-free survival
Clinical Progression-free survival and/or radiological Progression free survival will be evaluated
Measured: 5 years
Overall survival (OS)
evaluate the overall survival
Measured: 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)
Measured: 6 months
Toxicity (NCI-CTC v4)
all observed toxicities, graded according to NCI-CTC v4 and the SAE
Measured: 6 months
Quality of life (questionnaires)
Quality of life (QLQ-C30 questionnaires of EORTC) and OES18 questionnaires of EORTC
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2018
- Study start7 Mar 2019
- Primary completion15 Apr 2024
- Study completion29 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federation Francophone de Cancerologie Digestive
- Sponsor type
- University, hospital or other
- Collaborators
- Shire, Servier
- Responsible party
- Sponsor
- Investigators
- DAVID TOUGERON, Principal investigator, PRODIGE 62 - FFCD 1701
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03719924
- Sponsor's protocol ID
- PRODIGE 62 - OESIRI
- Acronym
- OESIRI
- Status last verified
- Jan 2025
- First submitted
- 26 Sep 2018
- Last updated
- 8 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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.
PubMed 31899122Tougeron 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.
PubMed 40876084
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03719924
- Acronym / sponsor ID
- OESIRI / PRODIGE 62 - OESIRI
- Conditions
- Squamous Cell Carcinoma
- Keywords
- ESCC NAL-IRI
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Federation Francophone de Cancerologie DigestiveUniversity, hospital or other
- Collaborators
- Shire, Servier
- Study start
- 7 Mar 2019 (actual)
- Primary completion
- 15 Apr 2024 (actual)
- Study completion
- 29 Sep 2024 (actual)
- First posted
- 25 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| arm A: ONIVYDE | Experimental | Drug: OnivydeONIVYDE 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 |
| Arm B: TAXOL | Active comparator | Drug: PaclitaxelTAXOL 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OnivydeAlso: no other intervention name to addonivyde will be administered first, followed by folinic acid or L-folinic acid and then 5-FU at D1 and D14. | Drug | arm A: ONIVYDE |
| PaclitaxelAlso: no other intervention name to addPaclitaxel : 80 mg/m2 IV during 60 minutes at D1, D8 and D15 | Drug | Arm B: TAXOL |
Primary outcome
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.
5 secondary outcomes
Progression-free survival
Time frame: 5 years
Overall survival (OS)
Time frame: 1 year
Best response rate during treatment
Time frame: 6 months
Toxicity (NCI-CTC v4)
Time frame: 6 months
Quality of life (questionnaires)
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2025.
- Background: PubMed 31899122Randrian 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.
- Derived from this study: PubMed 40876084Tougeron 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
DAVID TOUGERON principal investigator
PRODIGE 62 - FFCD 1701
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Onivyde and Paclitaxel in people with Squamous Cell Carcinoma, run by Federation Francophone de Cancerologie Digestive at 9 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
survival at 9 months (time frame: 9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03719924, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2025.