Radiochemotherapy With and Without Dose Escalation in Patients Presenting Locally Advanced or Inoperable Carcinoma of the Oesophagus (CONCORDE)
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%.
調査の概要
状態
条件
研究の種類
入学 (実際)
段階
- フェーズ2
- フェーズ 3
連絡先と場所
研究場所
-
-
-
Dijon、フランス、21000
- Centre Georges François Leclerc
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- Impossibility to adhere to the medical follow up for the trial for geographical,social or psychiatric reasons.
- Presence of a history of radiotherapy to the chest or upper abdomen for another tumour
- Peripheral neuropathy > or = grade 1 (CTC v3.0)
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
アクティブコンパレータ:ARM A
Conformal 3D Radiotherapy with " ENI "-type prophylactic irradiation of the lymph nodes:
|
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.
|
|
実験的:ARM B
Conformal 3D Radiotherapy with " ENI "-type prophylactic irradiation of the lymph nodes:
|
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.
|
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
|
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.
時間枠:end of phase II (january 2014)
|
end of phase II (january 2014)
|
|
Evaluate the rate of completes endoscopic response at 3 months
時間枠: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)
時間枠:after the end of phase III in january 2015 (anticipated)
|
after the end of phase III in january 2015 (anticipated)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Evaluate adherence
時間枠: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
時間枠:for each patient 3 months after the end treatment
|
for each patient 3 months after the end treatment
|
|
|
Evaluate death due to toxicity
時間枠: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])
時間枠: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])
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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)
|
協力者と研究者
協力者
捜査官
- 主任研究者:Gilles Créhange, MD、Centre Georges François Leclerc
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。