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

NCT01348217 | Completed Phase 2 DMC

• 1 other identifier: 0291-1crgi09
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 1

Brief Summary

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%.

Conditions

Esophageal Cancer

Keywords

unoperated cancers; oesophagus; radiochemotherapy; with and without increased doses

Outcome Measures

Primary Outcomes (3)

• 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.

  end of phase II (january 2014)

• Evaluate the rate of completes endoscopic response at 3 months

  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)

  after the end of phase III in january 2015 (anticipated)

Secondary Outcomes (13)

• Evaluate adherence

  every 3 months until the end of phase II (january 2014)

• Evaluate acute toxicity at 3 months

  for each patient 3 months after the end treatment

• Evaluate death due to toxicity

  each month during all the study

• Evaluate quality of life (QLQ-C30 [annex n° 2] + OG25 [annex n° 3])

  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])

  after the completion of phase III (january 2015-anticpated)

Study Arms (2)

ARM A

ACTIVE COMPARATOR

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; Radiation: Boost; Drug: chemotherapy: FOLFOX 4

ARM B

EXPERIMENTAL

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; Radiation: Boost; Drug: chemotherapy: FOLFOX 4

Interventions

Conformal 3D Radiotherapy with " ENI "-type prophylactic irradiation of the lymph node RADIATION

40 Gy in 20 fractions / 5 weeks, PTV (1cm in every direction)

ARM A; ARM B

Boost RADIATION

Boost 10 Gy in 5 fr, PTV = +1cm.

ARM A

chemotherapy: FOLFOX 4 DRUG

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.

ARM A; ARM B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Evolutive heart failure or myocardial necrosis for less than 6 months
• Myocardial infarction of more than 6 months with ischemic sequelae on myocardial scintigraphy.
• Patient cannot absorb at least 1500kcal/j before and/or during treatment
• Left heart failure.
• Stage II to IV arteriopathy in the Leriche and Fontaine classification
• Creatinine \> or = 1.25x N
• PNN \< 1,5.109 /l
• Platelets \< 100. 109 /l
• Albumin \< 30g/l
• TP \< 60% without anticoagulant
• VEMS \< 1l
• 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
• Patient already enrolled in another therapeutic trial with an experimental molecule
• Women who are pregnant or likely to be so, or who are breastfeeding
• People who are in custody or under guardianship

Sponsors & Collaborators

• Centre Georges Francois Leclerc: lead
• National Cancer Institute, France: collaborator
• UNICANCER: collaborator
• SFRO:French Society of Radiation Oncology: collaborator
• Federation Francophone de Cancerologie Digestive: collaborator

Study Sites (1)

Centre Georges François Leclerc

Dijon, 21000, France

Location

Related Publications (1)

• Bednarek C, Crehange G, Quivrin M, Cueff A, Vulquin N, Chevalier C, Cerda T, Petegnief Y, Mazoyer F, Maingon P, Bosset JF, Servagi Vernat S. Mapping of failures after radiochemotherapy in patients with non-metastatic esophageal cancer: A posteriori analysis of the dose distribution in the sites of loco-regional relapse. Radiother Oncol. 2015 Aug;116(2):252-6. doi: 10.1016/j.radonc.2015.07.019. Epub 2015 Jul 27.

  PMID: 26228970 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Gilles Créhange, MD

  Centre Georges Francois Leclerc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2011
• First Posted: May 5, 2011
• Study Start: May 6, 2011
• Primary Completion: June 7, 2011
• Study Completion: December 17, 2018
• Last Updated: January 27, 2020

Record last verified: 2020-01

Locations

FR (1)