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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 uppdaterad av: 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%.

Studieöversikt

Studietyp

Interventionell

Inskrivning (Faktisk)

196

Fas

  • Fas 2
  • Fas 3

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

      • Dijon, Frankrike, 21000
        • Centre Georges François Leclerc

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 75 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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)

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Aktiv komparator: 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.
Experimentell: 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.

Vad mäter studien?

Primära resultatmått

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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Evaluate adherence
Tidsram: 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
Tidsram: for each patient 3 months after the end treatment
for each patient 3 months after the end treatment
Evaluate death due to toxicity
Tidsram: 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])
Tidsram: 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])
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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)

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Utredare

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

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

6 maj 2011

Primärt slutförande (Faktisk)

7 juni 2011

Avslutad studie (Faktisk)

17 december 2018

Studieregistreringsdatum

Först inskickad

29 april 2011

Först inskickad som uppfyllde QC-kriterierna

4 maj 2011

Första postat (Uppskatta)

5 maj 2011

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

27 januari 2020

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

24 januari 2020

Senast verifierad

1 januari 2020

Mer information

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