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

24. januar 2020 oppdatert 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%.

Studieoversikt

Studietype

Intervensjonell

Registrering (Faktiske)

196

Fase

  • Fase 2
  • Fase 3

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

      • Dijon, Frankrike, 21000
        • Centre Georges François Leclerc

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 75 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / 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.
Eksperimentell: 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.

Hva måler studien?

Primære resultatmål

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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Evaluate adherence
Tidsramme: 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
Tidsramme: for each patient 3 months after the end treatment
for each patient 3 months after the end treatment
Evaluate death due to toxicity
Tidsramme: 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])
Tidsramme: 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])
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Etterforskere

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

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

6. mai 2011

Primær fullføring (Faktiske)

7. juni 2011

Studiet fullført (Faktiske)

17. desember 2018

Datoer for studieregistrering

Først innsendt

29. april 2011

Først innsendt som oppfylte QC-kriteriene

4. mai 2011

Først lagt ut (Anslag)

5. mai 2011

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

27. januar 2020

Siste oppdatering sendt inn som oppfylte QC-kriteriene

24. januar 2020

Sist bekreftet

1. januar 2020

Mer informasjon

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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