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Radiochemotherapy With and Without Dose Escalation in Patients Presenting Locally Advanced or Inoperable Carcinoma of the Oesophagus (CONCORDE)

24 janvier 2020 mis à jour par: Centre Georges Francois Leclerc

Prodige 26: Radiochemotherapy With and Without Dose Escalation in Patients Presenting Locally Advanced or Inoperable Carcinoma of the Oesophagus

Exclusive concomitant radiochemotherapy (RCT) at a dose of 50 Gy delivered over 5 weeks, according to the RTOG 85-01 protocol, has led to improved 5-year survival in 25% of patients, whereas no patients survived for 5 years using radiotherapy alone for patients with esophageal cancer. Surgery, even when combined with preoperative RCT, also gives disappointing results for locally advanced tumors, which casts serious doubts on the usefulness of preoperative radiotherapy. By varying the fractionation schedule, the length of treatment or the radiotherapy volumes, it has become possible to obtain levels of loco-regional relapse of around 35 to 45%. After reviewing the results for loco-regional relapse according to the dose of radiation and the recommended radiotherapy volumes, we aimed to investigate why increasing the dose of radiation has no impact in esophageal cancers. Although INT-0123 phase III trial showed no benefit of dose escalation in esophageal cancer, some issues remain unclear as most of the patients who died in the experimental arm were treated above 50Gy. Moreover, only the tumor was treated up to 64Gy while involved nodes were not considered for dose escalation in this trial. In the RTOG 85-01phase III trial, an elective nodal irradiation from subclavicular fossa up to the esophagogastric junction was performed with a 2D technique, delivering 30Gy which could be considered as not appropriate.

In this randomized phase II/III trial, we aim to test an exclusive concomitant chemoradiotherapy for patients with non resectable esophageal cancer with a dose escalation up to 66Gy on the primary tumor as well as the involved nodes using a 3D conformal technique combined with a 40 Gy elective nodal irradiation on lymph node stations (as defined by the RTOG) with a risk of microscopic involvement ≥ 20%.

Aperçu de l'étude

Type d'étude

Interventionnel

Inscription (Réel)

196

Phase

  • Phase 2
  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

      • Dijon, France, 21000
        • Centre Georges Francois Leclerc

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 75 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  1. Age> or = 18 and < 75 ans
  2. WHO Status 0, 1 and 2
  3. Enteral or parenteral feeding (> or = 1500 KCal) planned before the start of treatment
  4. Histologically proven carcinoma of the oesophagus
  5. Histological Types: adenocarcinomas and epidermoid carcinomas
  6. T3, N0-N1-N2-N3, M0 (TNM version 7)
  7. T1-T2, N0-N1-N2-N3, M0 with a contra-indication for surgery (TNM version 7)
  8. Absence of trachea-oesophageal fistula
  9. Written informed consent
  10. Woman under appropriate contraception
  11. Patient able to understand and complete, with help if necessary, a quality of life questionnaire

Exclusion Criteria:

  1. Evolutive heart failure or myocardial necrosis for less than 6 months
  2. Myocardial infarction of more than 6 months with ischemic sequelae on myocardial scintigraphy.
  3. Patient cannot absorb at least 1500kcal/j before and/or during treatment
  4. Left heart failure.
  5. Stage II to IV arteriopathy in the Leriche and Fontaine classification
  6. Creatinine > or = 1.25x N
  7. PNN < 1,5.109 /l
  8. Platelets < 100. 109 /l
  9. Albumin < 30g/l
  10. TP < 60% without anticoagulant
  11. VEMS < 1l
  12. History of cancer (except baso-cellular cutaneous epithelioma or in situ epithelioma of the cervix) that has relapsed in the 5 years preceding recruitment for the trial
  13. Patient already enrolled in another therapeutic trial with an experimental molecule
  14. Women who are pregnant or likely to be so, or who are breastfeeding
  15. People who are in custody or under guardianship
  16. Impossibility to adhere to the medical follow up for the trial for geographical,social or psychiatric reasons.
  17. Presence of a history of radiotherapy to the chest or upper abdomen for another tumour
  18. Peripheral neuropathy > or = grade 1 (CTC v3.0)

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur actif: ARM A

Conformal 3D Radiotherapy with " ENI "-type prophylactic irradiation of the lymph nodes:

  1. Radiotherapy 40 Gy, in 20 fractions / 4 weeks: PTV (1cm in every direction)
  2. Boost 10 Gy in 5 fr: PTV = +1cm.
  3. Chemotherapy FOLFOX 4: 6 treatments in 3 courses concomitant to the radiotherapy (D1, D15, D29)
40 Gy in 20 fractions / 5 weeks, PTV (1cm in every direction)
Boost 10 Gy in 5 fr, PTV = +1cm.
Boost 26 Gy in 13 fr, PTV = +1cm.
6 treatments with 4 courses concomitant to radiotherapy (D1, D15, D29, D43) arm B or 3 courses concomitant to radiotherapy (D1, D15, D29) arm A.
Expérimental: ARM B

Conformal 3D Radiotherapy with " ENI "-type prophylactic irradiation of the lymph nodes:

  1. 40 Gy in 20 fractions / 4 weeks, PTV (1cm in every direction)
  2. Boost 26 Gy in 13 fr: PTV = +1cm.
  3. Chemotherapy: FOLFOX 4: 6 treatments with 4 courses concomitant to radiotherapy (D1, D15, D29, D43).
40 Gy in 20 fractions / 5 weeks, PTV (1cm in every direction)
Boost 10 Gy in 5 fr, PTV = +1cm.
Boost 26 Gy in 13 fr, PTV = +1cm.
6 treatments with 4 courses concomitant to radiotherapy (D1, D15, D29, D43) arm B or 3 courses concomitant to radiotherapy (D1, D15, D29) arm A.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
Evaluate the rate of acute toxicity leading to cessation or temporary interruption of treatment of more than a total of 14 days or of 7 consecutive days during the whole treatment.
Délai: end of phase II (january 2014)
end of phase II (january 2014)
Evaluate the rate of completes endoscopic response at 3 months
Délai: for each patient 3 months after the end treatment
for each patient 3 months after the end treatment
Survival without locoregional relapse at 2 years (time elapsed between date of randomisation and onset of local relapse and/or lymph node involvement)
Délai: after the end of phase III in january 2015 (anticipated)
after the end of phase III in january 2015 (anticipated)

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Evaluate adherence
Délai: every 3 months until the end of phase II (january 2014)
every 3 months until the end of phase II (january 2014)
Evaluate acute toxicity at 3 months
Délai: for each patient 3 months after the end treatment
for each patient 3 months after the end treatment
Evaluate death due to toxicity
Délai: each month during all the study
each month during all the study
Evaluate quality of life (QLQ-C30 [annex n° 2] + OG25 [annex n° 3])
Délai: after the completion of phase II (january 2014)
after the completion of phase II (january 2014)
Compare according to treatment arm :Quality of life (QLQ-C30 [annex n° 2] + OG 25 [annex n° 3])
Délai: after the completion of phase III (january 2015-anticpated)
after the completion of phase III (january 2015-anticpated)
Compare according to treatment arm :Overall survival
Délai: after the completion of phase III (january 2015-anticpated)
after the completion of phase III (january 2015-anticpated)
Compare according to treatment arm :Disease-free survival
Délai: after the completion of phase III (january 2015-anticpated)
after the completion of phase III (january 2015-anticpated)
Compare according to treatment arm :Acute and late toxicity according to the CTCAE version 3.0 scale
Délai: after the completion of phase III (january 2015-anticpated)
after the completion of phase III (january 2015-anticpated)
Compare according to treatment arm :The number of palliative interventions, the time to the first palliative intervention
Délai: after the completion of phase III (january 2015-anticpated)
after the completion of phase III (january 2015-anticpated)
Compare according to treatment arm :The rate of dysphagia according to Atkinson's criteria
Délai: after the completion of phase III (january 2015-anticipated)
after the completion of phase III (january 2015-anticipated)
Compare according to treatment arm :Survival without local recurrence in responders
Délai: after the completion of phase III (january 2015-anticipated)
after the completion of phase III (january 2015-anticipated)
Compare according to treatment arm :Progression-free survival in non-responding patients
Délai: after the completion of phase III (january 2015-anticipated)
after the completion of phase III (january 2015-anticipated)
Evaluation of the post-operative morbi-mortalities
Délai: after the completion of phase III (january 2015-anticipated)
Evaluation of the post-operative morbi-mortalities (in 30 days) of the group of patients which will benefit from of a surgery of the tumoral residue.
after the completion of phase III (january 2015-anticipated)

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Les enquêteurs

  • Chercheur principal: Gilles Créhange, MD, Centre Georges Francois Leclerc

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

6 mai 2011

Achèvement primaire (Réel)

7 juin 2011

Achèvement de l'étude (Réel)

17 décembre 2018

Dates d'inscription aux études

Première soumission

29 avril 2011

Première soumission répondant aux critères de contrôle qualité

4 mai 2011

Première publication (Estimation)

5 mai 2011

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

27 janvier 2020

Dernière mise à jour soumise répondant aux critères de contrôle qualité

24 janvier 2020

Dernière vérification

1 janvier 2020

Plus d'information

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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