Radiation Therapy, Chemotherapy, and Cetuximab Followed by Surgery, Chemotherapy, and Cetuximab in Treating Patients With Locally Advanced or Metastatic Rectal Cancer That Can Be Removed by Surgery
Phase II Multicenter Study of the Impact of the Therapeutic Sequence of Radiochemotherapy (50 Gy + Capecitabine + Oxaliplatin + Cetuximab) Followed by Total Mesorectal Excision Surgery Then Post-surgery Chemotherapy (FOLFOX 4 + Cetuximab) in Synchronous Locally Advanced or Metastatic Cancers of the Rectum With Metastases Resectable From the Start (T3-4 Nx or T2 N+ M1).
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as capecitabine, oxaliplatin, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving radiation therapy together with combination chemotherapy and cetuximab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy and cetuximab after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase II clinical trial is studying how well giving radiation therapy together with chemotherapy and cetuximab followed by surgery, chemotherapy, and cetuximab works in treating patients with locally advanced or metastatic rectal cancer that can be removed by surgery.
調査の概要
状態
条件
詳細な説明
OBJECTIVES:
Primary
- Determine the complete remission rate at 6 months after neoadjuvant radiotherapy, capecitabine, and oxaliplatin (XELOX), and cetuximab followed by surgery, adjuvant FOLFOX 4, and cetuximab in patients with synchronous locally advanced or metastatic cancer of the rectum with resectable metastases (T3-4 Nx or T2 N+ M1).
Secondary
- Determine progression-free survival.
- Determine overall survival.
- Assess toxicities.
- Evaluate objective response in patients with measurable metastases.
- Determine the rate of local recurrence.
- Evaluate the downstaging and downsizing of patients with operable disease.
- Evaluate surgical complications in patients with operable disease.
- Evaluate biological markers predictive of response to cetuximab.
OUTLINE: This is a multicenter study.
- Neoadjuvant therapy: Patients undergo radiotherapy for 5 weeks and receive concurrent oral capecitabine twice daily on days 1-5 of each week and oxaliplatin IV over 2 hours on day 1 of each week (XELOX). Patients also receive cetuximab IV on day 1 of the first week and on days 1-7 of weeks 2-5.
- Surgery: At 6 weeks after completing chemoradiotherapy, patients with resectable disease undergo surgery comprising total mesorectal excision. Patients with progressive disease, nonresectable tumor, or who require R2 surgery are removed from the study.
- Adjuvant therapy: Patients who undergo surgery, with or without removal of metastases, receive FOLFOX 4, comprising oxaliplatin IV over 2 hours, fluorouracil IV over 46 hours, and leucovorin calcium IV on day 1, and cetuximab IV. Treatment repeats every 2 weeks for up to 6 courses (approximately 3 months). Patients who have not undergone prior surgical resection of metastases may have surgery to remove metastases after completing this second regimen of chemotherapy.
After completion of study therapy, patients are followed periodically for up to 5 years.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
-
-
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Bordeaux、フランス、33076
- Institut Bergonie
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Dijon、フランス、21079
- Centre de Lutte Contre le Cancer Georges-Francois Leclerc
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Lille、フランス、59020
- Centre Oscar Lambret
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Lyon、フランス、69373
- Centre Leon Berard
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Montpellier、フランス、34298
- Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
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Nice、フランス、06189
- Centre Antoine Lacassagne
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Pierre Benite、フランス、69495
- Centre Hospitalier Lyon Sud
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Saint Cloud、フランス、92210
- Centre Rene Huguenin
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Vandoeuvre-les-Nancy、フランス、54511
- Centre Alexis Vautrin
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Villejuif、フランス、F-94805
- Institut Gustave Roussy
-
-
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
DISEASE CHARACTERISTICS:
Histologically confirmed adenocarcinoma of the rectum
Locally advanced (T3-4 Nx) or metastatic (T2 N+ M1) synchronous disease
- Metastases must be resectable
- Primary tumor examined by endorectal echography and MRI
- Measurable disease by thoraco-abdomino-pelvic scanner
- Disease considered susceptible to treatment with radiotherapy and chemotherapy
- No diffuse metastases considered nonresectable
- No acute occlusion not caused by colostomy
PATIENT CHARACTERISTICS:
Inclusion criteria:
- ECOG performance status 0-2
- WBC ≥ 4,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 10 g/dL
- Creatinine ≤ 130 µmol/L
- Transaminases ≤ 5 times upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients of must use effective contraception
Exclusion criteria:
- Contraindication to therapy with capecitabine, oxaliplatin, cetuximab, and/or radiotherapy
- Impossible to perform translational analyses
- Uncontrolled severe illness
- Severe renal or hepatic insufficiency
- Cardiac insufficiency or symptomatic coronary disease
- Sensitive peripheral neuropathy
- Uncontrolled diabetes
- Other malignancy within the past 10 years except previously treated basal cell skin cancer or carcinoma in situ of the cervix
- Impossible to participate in study due to geographic, social, or psychiatric reasons
- Patients who are under supervision or incarcerated
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior anticancer chemotherapy or radiotherapy for this cancer
- No therapy with coumarin anticoagulants, phenytoin, sorivudine, brivudine, antacids, or allopurinol
- No concurrent participation in another therapeutic study or receiving another experimental drug
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:非ランダム化
- 介入モデル:単一グループの割り当て
- マスキング:なし(オープンラベル)
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 |
---|
Complete remission at ≥ 6 months by abdomino-pelvic-thoracic scan and a pelvic MRI
|
二次結果の測定
結果測定 |
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無増悪生存
|
全生存
|
性機能
|
後期毒性
|
手術の合併症
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括約筋機能
|
Preoperative clinical response
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Early toxicity before surgery
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Early toxicity due to surgery (mortality at 30 days, postoperative complications, surgical recovery)
|
Late radiotherapy toxicity by CTC AE v. 3.0
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Objective response of measurable metastases by RECIST
|
Downstaging and downsizing of patients with operable disease
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Predictive biomarkers of response to cetuximab
|
協力者と研究者
スポンサー
捜査官
- 主任研究者:David Azria, MD, PhD、Institut du Cancer de Montpellier - Val d'Aurelle
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
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- CDR0000565937
- FRE-FNCLCC-ACCORD-14/0604 (その他の識別子:FNCLCC)
- EU-20759
- 2006-003336-30 (EudraCT番号)
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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大腸がんの臨床試験
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