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Esophagus CancerPhase 2ARIONNCT03777813

Association of Radiochemotherapy and Immunotherapy for the Treatment of Unresectable Oesophageal caNcer

A Phase 2 study testing Durvalumab and IMRT 50 Gy + FOLFOX4 simplifIed (oxaliplatin, leucovorin, 5-FU) in people with Esophagus Cancer and Unresectable Malignant Neoplasm, run by UNICANCER at 7 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study aims to assess the efficacy of durvalumab in combination with radiochemotherapy (FOLFOX and IMRT) and then as maintenance therapy for treating patients with localised unresectable oesophageal cancer. This is a randomized, French national, multicentre, comparative phase II trial Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Durvalumab and IMRT 50 Gy + FOLFOX4 simplifIed (oxaliplatin, leucovorin, 5-FU)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
112 participants
Where
7 sitesFrance
Study dates
5 Dec 2018to 1 Dec 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 squamous cell carcinoma or adenocarcinoma of the oesophagus,
  • Unresectable disease due to anatomical consideration or medical condition (patient unfit for surgical procedure),
  • Presence of at least one measurable lesion >10 mm with spiral CT scan,
  • No prior therapy for pathology investigated including chemotherapy or radiotherapy prior to the study, except anterior out of field radiotherapy, received for treatment of another primary tumor considered in remission, in the past 5 years,
  • Age ≥18 years old,
  • WHO performance status <2 (i.e., 0 or 1),
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  • Body weight >35 kg,
  • Life expectancy of at least 12 weeks ,
  • Adequate haematology laboratory data within the 7 days before randomization
  • Absolute neutrophils >1.5 x 109/L
  • Platelets >100 x 109/L
  • Haemoglobin ≥9 g/dL,
  • Adequate Biochemistry laboratory data within the 7 days before randomization
  • Total bilirubin ≤1.5 x upper limit of normal (ULN)
  • Transaminases ≤2.5 x ULN
  • Alkaline phosphatases ≤5 x ULN,
  • Measured creatinine clearance (CL) >40 mL/min by the Cockcroft-Gault formula,
  • Glycaemia ≤1.5 x ULN
  • Cholesterolaemia ≤7.30 mmol/L,
  • Albumin >28 g/L
  • Adequate haemostasis laboratory data within 7 days prior to randomization: prothrombin time (PT) within the normal range,
  • Adequate values for calcium, potassium and magnesium levels measured within 7 days prior to randomization,
  • Women should be post-menopaused or willing to accept the use an effective contraceptive regimen during the treatment period and for at least 6 months after the end of the study. All non-menopausal women should have a negative pregnancy test within 72 h prior to randomization. Men should accept to use an effective contraception during treatment period and at least 6 months after the end of the study especially after the last dose of oxaliplatin treatment.
  • Patients must have provided consent for the study by signing and dating a written informed consent form prior to any study specific procedures, sampling, or analyses,
  • Patient affiliated to a social security regimen.
  • Uracilemia < 16ng/ml
  • Forced expiratory volume (FEV) >1 liter or > 50% of the theoretical value

Who cannot join

  • Previous treatment with another PD-1, PD-L1 including durvalumab or CTLA-4 inhibitor
  • Metastatic disease,
  • Patients should not receive live vaccine 30 days prior to study drug
  • Female patients who are pregnant or breastfeeding
  • Uncontrolled intercurrent illness including, but not limited to diabetes, hypertension, pulmonary failure, chronic renal or hepatic diseases, active peptic ulcer disease or gastritis, active bleeding, diatheses... (non-exhaustive list),
  • Clinically significant cardiac disease or impaired cardiac function, such as:
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  • Congestive heart failure requiring treatment (New York Heart Association [NYHA] grade ≥2), left ventricular ejection fraction (LVEF) <50% as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO), or uncontrolled arterial hypertension defined by blood pressure >140/100 mmHg at rest (average of 3 consecutive readings),
  • History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high- grade/complete AV-blockage,
  • Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting), <3 months prior to screening,
  • MeanQT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction.
  • Current or prior use of immunosuppressive medication within 28 days before the first administration of durvalumab (exception: systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or equivalent are allowed as well as steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) - Topical, inhaled, nasal, and ophthalmic steroids are allowed,
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stabilised with hormone replacement therapy
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with coeliac disease controlled by diet alone
  • Known primary immunodeficiency or active HIV,
  • Patient with a dihydropyrimidine dehydrogenase (DPD) deficiency (Uracilemia ≥ 16 ng/ml, the test should be done for all patients before 5-FU administration)* ,
  • Known active or chronic viral hepatitis or history of any type of hepatitis within the last 6 months indicated by positive HBS antibody test for hepatitis B or hepatitis C virus ribonucleic acid (HCV antibody),
  • History of organ transplantation requiring the use of immunosuppressive medication, including allogenic stem cell transplant
  • History of active tuberculosis or latent disease capable of reactivation,
  • Current pneumonitis or interstitial lung disease,
  • Other invasive malignancy within 2 years prior to entry into the study, except for those treated with surgical therapy only,
  • History of severe allergic reactions or hypersensitivity to any unknown allergens or any components of the study drug (refer to IB of durvalumab section 5.5.1.11).
  • Any prior corticosteroid-refractory immune-related adverse event (irAE),
  • Oeso-tracheal or oeso-bronchial fistulae,
  • Major surgery within 28 days prior to the first dose of study treatment
  • Toxicities of grade ≥1 from any previous therapy,
  • Peripheral sensory neuropathy with functional impairment
  • Severe infection requiring parenteral antibiotic treatment
  • Patients treated with sorivudine or analogues as brivudine
  • Patients treated with phenytoin for prophylaxis
  • Participation in another therapeutic trial within the 30 days prior to study inclusion,
  • Patients deprived of liberty or under guardianship,
  • Patients unable to adhere to the protocol for geographical, social, or psychological reasons.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

France7 sites

  • Centre Oscar Lambret, CLCC UNICANCER

    Lille

  • Hôpital Saint Louis, APHP

    Paris, 75010

  • Hôpital Haut-Lévêque

    Pessac, 33604

  • Centre Hospitalier Universitaire

    Poitiers

  • Centre Paul Strauss, CLCC UNICANCER

    Strasbourg

  • Iuct, Clcc Unicancer

    Toulouse, 31059

  • CHU Rangueil Larrey

    Toulouse

Other trials in France

About this study

Official title: Association of Radiochemotherapy and Immunotherapy for the Treatment of Unresectable Oesophageal caNcer: a Comparative Randomized Phase II Trial

This study aims to assess the efficacy of durvalumab in combination with radiochemotherapy (FOLFOX and IMRT) and then as maintenance therapy for treating patients with localised unresectable oesophageal cancer. This is a randomized, French national, multicentre, comparative phase II trial

Read the detailed description

ARION study will randomize 120 patients, in 12 centers in France, according to a ratio 1:1 in the following arm of treatment:

  • Standard and experimental arm:

Definitive modulated-intensity radiotherapy will be delivered according to boost integrated technique 5 days a week for 5 weeks at a dose of:

  • 50 Gy delivered in 25 fractions to the macroscopic disease (endoscopic, TDM and fused FDG PET)
  • 45 Gy to the adjacent peri tumoral mucosis and prophylactic lymph node

FOLFOX 4 simplified protocol, 1 infusion every 2 weeks (q2w) during 3 months starting with radiotherapy (+/- 1 day):

  • IV oxaliplatin 85 mg/m² in 2 h on day 1 (D1)
  • IV Leucovorin 200 mg/m² in 2 h on D1, followed by
  • IV 5-FU 400 mg/m² in 10 minutes on D1 followed by
  • IV continuous infusion 5-FU 2400 mg/m² in 46 h
  • Experimental arm: Concomitant administration of durvalumab:

Every 4 weeks during concurrent FOLFOX (dose: 1500 mg) and after FOLFOX completion (total of 12 months of treatment).

Being tested
Durvalumab, IMRT 50 Gy + FOLFOX4 simplifIed (oxaliplatin, leucovorin, 5-FU)
Keywords
oesophagus, localised unresectable, adenocarcinoma or squamous cell carcinoma, durvalumab, FOLFOX 4 simplified, Definitive modulated-intensity radiotherapy
Medical subject headings
Esophageal Neoplasms, Adenocarcinoma, Carcinoma, Squamous Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DurvalumabDrug

    Also called IMRT 50 Gy + FOLFOX4 simplifIed (oxaliplatin, leucovorin, 5-FU)

    Radiochemotherapy in standard arm and in experimental arm: 10 weeks (RT 50 Gy and FOLFOX q2w) Immunotherapy in experimental arm only: Patients will received concomitantly a maximum of 12 infusions

  • IMRT 50 Gy + FOLFOX4 simplifIed (oxaliplatin, leucovorin, 5-FU)Combination product

    Radiochemotherapy in standard arm and in experimental arm: 10 weeks (RT 50 Gy and FOLFOX q2w)

Study groups in NCT03777813
Study groupRoleWhat they receive
Arm AExperimentalConcomitant administration of durvalumab (dose: 1500 mg): Every 4 weeks during concurrent FOLFOX and after FOLFOX completion (total of 12 months of treatment) Definitive modulated-intensity radiotherapy will be delivered according to boost integrated technique 5 days a week for 5 weeks at a dose of: * 50 Gy delivered in 25 fractions to the macroscopic disease (endoscopic, TDM and fused FDG PET) * 45 Gy to the adjacent peri tumoral mucosis and prophylactic lymph node FOLFOX 4 simplified protocol, 1 infusion every 2 weeks during 3 months starting with radiotherapy (+/- 1 day): * IV oxaliplatin 85 mg/m² in 2 h on D1 * IV Leucovorin 200 mg/m² in 2 h on D1, followed by * IV 5-FU 400 mg/m² in 10 minutes on D1 followed by * IV continuous infusion 5-FU 2400 mg/m² in 46 h
Receives: Drug: Durvalumab; Combination Product: IMRT 50 Gy + FOLFOX4 simplifIed (oxaliplatin, leucovorin, 5-FU)
Arm BActive comparatorDefinitive modulated-intensity radiotherapy will be delivered according to boost integrated technique 5 days a week for 5 weeks at a dose of: * 50 Gy delivered in 25 fractions to the macroscopic disease (endoscopic, TDM and fused FDG PET) * 45 Gy to the adjacent peri tumoral mucosis and prophylactic lymph node FOLFOX 4 simplified protocol, 1 infusion every 2 weeks during 3 months starting with radiotherapy (+/- 1 day): * IV oxaliplatin 85 mg/m² in 2 h on D1 * IV Leucovorin 200 mg/m² in 2 h on D1, followed by * IV 5-FU 400 mg/m² in 10 minutes on D1 followed by * IV continuous infusion 5-FU 2400 mg/m² in 46 h
Receives: Combination Product: IMRT 50 Gy + FOLFOX4 simplifIed (oxaliplatin, leucovorin, 5-FU)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. cPFS (centrally reviewed cPFS)

    defined by a blinded independent centralized revue of progression free survival. cPFS is defined as the time from randomization until progression or death; patients alive and without documented progression at last follow-up news have PFS censored at this date or at initiation of new anticancer treatment (if applicable). Progression will be defined with central external reviewing of TDM per RECIST v1.1

    Measured: 12-months cPFS

Secondary outcomes (3)

  1. Overall survival (OS)

    defined as the time between randomization and death due to any cause.

    Measured: For each treatment arms, survival rates (PFS and OS) will be estimated at 12, 18 and 24 months

  2. Adverse Events

    will be assessed on occurrence of Adverse Events (AEs) based on NCI CTCAE v5.0

    Measured: 2 years after randomization

  3. Quality of Life OES18, used for patients with oesophageal cancer always complemented by the QLQ-C30 measuring 5 functional scales (physical, everyday activity, cognitive, emotional and social) and 3 symptoms scales (fatigue, pain, nausea and vomiting)

    scores EORTC QLQ C30 - OES18

    Measured: 2 years after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Dec 2018
  2. Study start5 Dec 2018
  3. Primary completion24 May 2024
  4. Study completion1 Dec 2024

Resources

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
Masking
None (open label)
Enrolment
112 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03777813
Sponsor's protocol ID
UC-110/1719 -PRODIGE 67-UCGI33
Other IDs
2018-000708-40, 2018
Acronym
ARION
Status last verified
Sep 2024
First submitted
11 Dec 2018
Last updated
18 Nov 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab and IMRT 50 Gy + FOLFOX4 simplifIed (oxaliplatin, leucovorin, 5-FU) in people with Esophagus Cancer and Unresectable Malignant Neoplasm, run by UNICANCER at 7 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 27 inclusion and 36 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 18 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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?

cPFS (centrally reviewed cPFS) (time frame: 12-months cPFS). 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 NCT03777813.

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 18 Nov 2025.

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