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

This study is currently recruiting participants.
Verified September 2012 by Centre Georges Francois Leclerc
Sponsor:
Collaborators:
National Cancer Institute, France
UNICANCER
SFRO:French Society of Radiation Oncology
FFCD
Information provided by (Responsible Party):
Centre Georges Francois Leclerc
ClinicalTrials.gov Identifier:
NCT01348217
First received: April 29, 2011
Last updated: September 24, 2012
Last verified: September 2012
History of Changes
  Purpose

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%.


Condition Intervention Phase
Esophageal Cancer
 Radiation: Conformal 3D Radiotherapy with " ENI "-type prophylactic irradiation of the lymph node
Radiation: Boost
Drug: chemotherapy: FOLFOX 4
 Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prodige 26: Radiochemotherapy With and Without Dose Escalation in Patients Presenting Locally Advanced or Inoperable Carcinoma of the Oesophagus

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Centre Georges Francois Leclerc:

Primary Outcome Measures:
  • 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. [ Time Frame: end of phase II (january 2014) ] [ Designated as safety issue: Yes ]
  • Evaluate the rate of completes endoscopic response at 3 months [ Time Frame: for each patient 3 months after the end treatment ] [ Designated as safety issue: No ]
  • Survival without locoregional relapse at 2 years (time elapsed between date of randomisation and onset of local relapse and/or lymph node involvement) [ Time Frame: after the end of phase III in january 2015 (anticipated) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate adherence [ Time Frame: every 3 months until the end of phase II (january 2014) ] [ Designated as safety issue: No ]
  • Evaluate acute toxicity at 3 months [ Time Frame: for each patient 3 months after the end treatment ] [ Designated as safety issue: Yes ]
  • Evaluate death due to toxicity [ Time Frame: each month during all the study ] [ Designated as safety issue: Yes ]
  • Evaluate quality of life (QLQ-C30 [annex n° 2] + OG25 [annex n° 3]) [ Time Frame: after the completion of phase II (january 2014) ] [ Designated as safety issue: No ]
  • Compare according to treatment arm :Quality of life (QLQ-C30 [annex n° 2] + OG 25 [annex n° 3]) [ Time Frame: after the completion of phase III (january 2015-anticpated) ] [ Designated as safety issue: No ]
  • Compare according to treatment arm :Overall survival [ Time Frame: after the completion of phase III (january 2015-anticpated) ] [ Designated as safety issue: No ]
  • Compare according to treatment arm :Disease-free survival [ Time Frame: after the completion of phase III (january 2015-anticpated) ] [ Designated as safety issue: No ]
  • Compare according to treatment arm :Acute and late toxicity according to the CTCAE version 3.0 scale [ Time Frame: after the completion of phase III (january 2015-anticpated) ] [ Designated as safety issue: Yes ]
  • Compare according to treatment arm :The number of palliative interventions, the time to the first palliative intervention [ Time Frame: after the completion of phase III (january 2015-anticpated) ] [ Designated as safety issue: No ]
  • Compare according to treatment arm :The rate of dysphagia according to Atkinson's criteria [ Time Frame: after the completion of phase III (january 2015-anticipated) ] [ Designated as safety issue: No ]
  • Compare according to treatment arm :Survival without local recurrence in responders [ Time Frame: after the completion of phase III (january 2015-anticipated) ] [ Designated as safety issue: No ]
  • Compare according to treatment arm :Progression-free survival in non-responding patients [ Time Frame: after the completion of phase III (january 2015-anticipated) ] [ Designated as safety issue: No ]
  • Evaluation of the post-operative morbi-mortalities [ Time Frame: after the completion of phase III (january 2015-anticipated) ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 252
Study Start Date: March 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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)
 Radiation: Conformal 3D Radiotherapy with " ENI "-type prophylactic irradiation of the lymph node
40 Gy in 20 fractions / 5 weeks, PTV (1cm in every direction)
Radiation: Boost
Boost 10 Gy in 5 fr, PTV = +1cm.
Drug: 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.
Experimental: 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).
 Radiation: Conformal 3D Radiotherapy with " ENI "-type prophylactic irradiation of the lymph node
40 Gy in 20 fractions / 5 weeks, PTV (1cm in every direction)
Radiation: Boost
Boost 26 Gy in 13 fr, PTV = +1cm.
Drug: 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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 ou M1a
  7. T1-T2, N0-N1-N2-N3, M0 or M1a with a contra-indication for surgery
  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%
  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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01348217

Contacts
Contact: Jérémy SKRZYPSKI, PHD 3 80 73 75 00 (3461) ext +33 jskrzypski@cgfl.fr
Contact: Sandrine Tiago 3 45 34 80 51 ext +33 stiago@cgfl.fr

Locations
France
Centre Georges François Leclerc Recruiting
Dijon, France, 21000
Contact: Gilles CREHANGE, MD     3 80 73 75 18 ext +33     gcrehange@cgfl.fr    
Sponsors and Collaborators
Centre Georges Francois Leclerc
National Cancer Institute, France
UNICANCER
SFRO:French Society of Radiation Oncology
FFCD
Investigators
Principal Investigator: Gilles Créhange, MD Centre Georges Francois Leclerc
  More Information

No publications provided

Responsible Party: Centre Georges Francois Leclerc
ClinicalTrials.gov Identifier: NCT01348217     History of Changes
Other Study ID Numbers: 0291-1crgi09
Study First Received: April 29, 2011
Last Updated: September 24, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Georges Francois Leclerc:
unoperated cancers
oesophagus
radiochemotherapy
with and without increased doses

Additional relevant MeSH terms:
Carcinoma
Esophageal Diseases
Esophageal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
 Gastrointestinal Diseases
Digestive System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms

ClinicalTrials.gov processed this record on June 13, 2013