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

24 januari 2020 bijgewerkt door: 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%.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Werkelijk)

196

Fase

  • Fase 2
  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Frankrijk
      • Dijon, Frankrijk, 21000
        • Centre Georges François Leclerc

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 75 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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)

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Actieve vergelijker: 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)
Straling: Conformal 3D Radiotherapy with " ENI "-type prophylactic irradiation of the lymph node
40 Gy in 20 fractions / 5 weeks, PTV (1cm in every direction)
Straling: Boost
Boost 10 Gy in 5 fr, PTV = +1cm.
Straling: Boost
Boost 26 Gy in 13 fr, PTV = +1cm.
Geneesmiddel: chemotherapy: FOLFOX 4
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.
Experimenteel: 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).
Straling: Conformal 3D Radiotherapy with " ENI "-type prophylactic irradiation of the lymph node
40 Gy in 20 fractions / 5 weeks, PTV (1cm in every direction)
Straling: Boost
Boost 10 Gy in 5 fr, PTV = +1cm.
Straling: Boost
Boost 26 Gy in 13 fr, PTV = +1cm.
Geneesmiddel: chemotherapy: FOLFOX 4
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.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
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.
Tijdsspanne: end of phase II (january 2014)
end of phase II (january 2014)
Evaluate the rate of completes endoscopic response at 3 months
Tijdsspanne: 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)
Tijdsspanne: after the end of phase III in january 2015 (anticipated)
after the end of phase III in january 2015 (anticipated)

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Evaluate adherence
Tijdsspanne: 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
Tijdsspanne: for each patient 3 months after the end treatment
for each patient 3 months after the end treatment
Evaluate death due to toxicity
Tijdsspanne: 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])
Tijdsspanne: 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])
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Centre Georges Francois Leclerc

Medewerkers

Federation Francophone de Cancerologie Digestive
National Cancer Institute, France
UNICANCER
SFRO:French Society of Radiation Oncology

Onderzoekers

  • Hoofdonderzoeker: Gilles Créhange, MD, Centre Georges François Leclerc

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

6 mei 2011

Primaire voltooiing (Werkelijk)

7 juni 2011

Studie voltooiing (Werkelijk)

17 december 2018

Studieregistratiedata

Eerst ingediend

29 april 2011

Eerst ingediend dat voldeed aan de QC-criteria

4 mei 2011

Eerst geplaatst (Schatting)

5 mei 2011

Updates van studierecords

Laatste update geplaatst (Werkelijk)

27 januari 2020

Laatste update ingediend die voldeed aan QC-criteria

24 januari 2020

Laatst geverifieerd

1 januari 2020

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 0291-1crgi09

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