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

NCT03777813 | Completed Phase 2

• 2 other identifiers: UC-110/1719 -PRODIGE 67-UCGI332018-000708-40
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 7

Brief 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

Conditions

Esophagus Cancer; Unresectable Malignant Neoplasm

Keywords

oesophagus; localised unresectable; adenocarcinoma or squamous cell carcinoma; durvalumab; FOLFOX 4 simplified; Definitive modulated-intensity radiotherapy

Outcome Measures

Primary Outcomes (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

  12-months cPFS

Secondary Outcomes (3)

• Overall survival (OS)

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

• Adverse Events

  2 years after randomization

• 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)

  2 years after randomization

Study Arms (2)

Arm A

EXPERIMENTAL

Concomitant 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

Drug: Durvalumab; Combination Product: IMRT 50 Gy + FOLFOX4 simplifIed (oxaliplatin, leucovorin, 5-FU)

Arm B

ACTIVE COMPARATOR

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

Combination Product: IMRT 50 Gy + FOLFOX4 simplifIed (oxaliplatin, leucovorin, 5-FU)

Interventions

Durvalumab DRUG

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

Also known as: IMRT 50 Gy + FOLFOX4 simplifIed (oxaliplatin, leucovorin, 5-FU)

Arm A

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)

Arm A; Arm B

Eligibility Criteria

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

You may qualify if:

• 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),
• 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

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (7)

Centre Oscar Lambret, CLCC UNICANCER

Lille, France

Location

Hôpital Saint Louis, APHP

Paris, 75010, France

Location

Hôpital Haut-Lévêque

Pessac, 33604, France

Location

Centre Hospitalier Universitaire

Poitiers, France

Location

Centre Paul Strauss, CLCC UNICANCER

Strasbourg, France

Location

Iuct, Clcc Unicancer

Toulouse, 31059, France

Location

CHU Rangueil Larrey

Toulouse, France

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Adenocarcinoma; Carcinoma, Squamous Cell

Interventions

durvalumab; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Anouchka Modesto, Doctor

  Institut Claudius Regaud

  PRINCIPAL INVESTIGATOR

• Laurent Quero, Doctor

  Hôpital Saint Louis / Université Paris Diderot

  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

Study Record Dates

• First Submitted: December 11, 2018
• First Posted: December 17, 2018
• Study Start: December 5, 2018
• Primary Completion: May 24, 2024
• Study Completion: December 1, 2024
• Last Updated: November 18, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.
• Access Criteria: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.

Locations

FR (7)