Combination Chemotherapy With or Without Cetuximab Before and After Surgery in Treating Patients With Resectable Liver Metastases Caused By Colorectal Cancer
A Prospective Randomised Open Label Trial of Oxaliplatin/Fluoropyrimidine Versus Oxaliplatin/Fluoropyrimidine Plus Cetuximab Pre and Post Operatively in Patients With Resectable Colorectal Liver Metastasis Requiring Chemotherapy
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, leucovorin, and capecitabine, 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 combination chemotherapy together with monoclonal antibodies before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery. It is not yet known whether combination chemotherapy is more effective with or without cetuximab in treating liver metastases caused by colorectal cancer.
PURPOSE: This randomized phase III trial is studying combination chemotherapy to compare how well it works when given with or without cetuximab before and after surgery in treating patients with resectable liver metastases caused by colorectal cancer.
調査の概要
状態
詳細な説明
OBJECTIVES:
Primary
- Compare progression-free survival of patients with resectable colorectal liver metastases treated with neoadjuvant and adjuvant combination chemotherapy with vs without cetuximab.
Secondary
- Compare the overall survival of patients treated with these regimens.
- Compare the quality of life of patients treated with these regimens.
- Compare the cost effectiveness of these regimens in these patients.
OUTLINE: This is a prospective, randomized, multicenter, open-label study. Patients are stratified according to participating center and assigned chemotherapy regimen. Patients are randomized to 1 of 2 treatment arms.
Neoadjuvant therapy:
Arm I: Patients receive 1 of the following chemotherapy regimens:
- OxMdG: Patients receive leucovorin calcium IV over 2 hours and oxaliplatin IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- CAPOX: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Arm II: Patients receive 1 of the following regimens:
- OxMdG + cetuximab: Patients receive cetuximab IV over 1-2 hours on day 1 and OxMdG chemotherapy as in arm I. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- CAPOX + cetuximab: Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and CAPOX chemotherapy as in arm I. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- Surgery: Beginning 2-6 weeks after completion of chemotherapy, patients in both arms undergo liver resection.
Adjuvant therapy: Beginning 4-8 weeks after completion of surgery, patients receive treatment (OxMdG or CAPOX with or without cetuximab) as in arm I or II of neoadjuvant therapy.
- Arm I: Treatment with OxMdG repeats every 2 weeks for up to 6 courses and treatment with CAPOX repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Treatment with OxMdG + cetuximab repeats every 2 weeks for up to 6 courses and treatment with CAPOX + cetuximab repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, every 12 weeks during chemotherapy, at completion of study treatment, every 3 months for 1 year, and then every 6 months thereafter.
Cost per life year and per quality-adjusted life year is assessed at baseline, every 12 weeks during treatment, and then at 3, 5, and 10 years.
After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
研究の種類
入学 (予想される)
段階
- フェーズ 3
連絡先と場所
研究場所
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England
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Basildon、England、イギリス、SS16 5NL
- 募集
- Basildon University Hospital
-
コンタクト：
- Pauline Leonard, MD
- 電話番号：44-1702-435-555
-
Basingstoke、England、イギリス、RG24 9NA
- 募集
- Basingstoke and North Hampshire NHS Foundation Trust
-
コンタクト：
- Charlotte Rees, MD
- 電話番号：44-125-631-4793
-
Bournemouth、England、イギリス、BH7 7DW
- 募集
- Royal Bournemouth Hospital
-
コンタクト：
- Tamas Hickish, MD
- 電話番号：44-1202-303-626
- メール：tamas.hickish@rbch.nhs.uk
-
Cambridge、England、イギリス、CB2 0QQ
- 募集
- Addenbrooke's Hospital
-
コンタクト：
- Pippa Corrie, PhD, FRCP
- 電話番号：44-1223-274-401
- メール：pippa.corrie@addenbrookes.nhs.uk
-
Guildford、England、イギリス、GU2 7XX
- 募集
- St. Luke's Cancer Centre at Royal Surrey County Hospital
-
コンタクト：
- Sharadah Essapen, MD
- 電話番号：44-1483-571-122
-
Liverpool、England、イギリス、L9 7AL
- 募集
- Aintree University Hospital
-
コンタクト：
- Graeme J. Poston, MD
- 電話番号：44-151-525-5980
- メール：graeme.poston@aintree.nhs.uk
-
Liverpool、England、イギリス、L9 7AL
- 募集
- Royal Liverpool University Hospital
-
コンタクト：
- Paula Ghaneh, MD
-
London、England、イギリス、SW3 6JJ
- 募集
- Royal Marsden - London
-
コンタクト：
- David Cunningham, MD
- 電話番号：44-20-8661-3156
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London、England、イギリス、EC1A 7BE
- 募集
- Saint Bartholomew's Hospital
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London、England、イギリス、W6 8RF
- 募集
- Charing Cross Hospital
-
コンタクト：
- Charles P. Lowdell, MD, BSc, MBBS, FRCP, FRCR
- 電話番号：44-208-383-0576
- メール：charles.lowdell@imperial.nhs.uk
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London、England、イギリス、NW3 2PF
- 募集
- UCL Cancer Institute
-
コンタクト：
- Astrid Mayer, MD
- 電話番号：44-207-794-0500
- メール：a.mayer@ucl.ac.uk
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Merseyside、England、イギリス、CH63 4JY
- 募集
- Clatterbridge Centre for Oncology
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Newport、England、イギリス、PO30 5TG
- 募集
- St. Mary's Hospital
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コンタクト：
- Christopher Baughan, MD
- 電話番号：44-1983-524-081
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Nottingham、England、イギリス、NG5 1PB
- 募集
- Cancer Research Centre at Weston Park Hospital
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コンタクト：
- J. Hornbuckle, MD
- 電話番号：44-115-969-1169 ext. 47599
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Poole Dorset、England、イギリス、BH15 2JB
- 募集
- Dorset Cancer Centre
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コンタクト：
- Tamas Hickish, MD
- 電話番号：44-1202-442-532
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Salisbury、England、イギリス、SP2 8BJ
- 募集
- Salisbury District Hospital
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Southampton、England、イギリス、SO16 6YD
- 募集
- Southampton General Hospital
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コンタクト：
- John N. Primrose, MD
- 電話番号：44-23-8079-6144
- メール：j.n.primrose@soton.ac.uk
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Sutton、England、イギリス、SM2 5PT
- 募集
- Royal Marsden - Surrey
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Westcliff-On-Sea、England、イギリス、SS0 0RY
- 募集
- Southend University Hospital NHS Foundation Trust
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コンタクト：
- Pauline Leonard, MD
- 電話番号：44-1702-435-555
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Worthing、England、イギリス、BN11 2DH
- 募集
- Worthing Hospital
-
コンタクト：
- Andrew Webb, MD
- 電話番号：44-1903-205-111
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Wales
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Cardiff、Wales、イギリス、CF14 2TL
- 募集
- Velindre Cancer Center at Velindre Hospital
-
コンタクト：
- Timothy Maughan, MD
- 電話番号：44-2920-316-904
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Cardiff、Wales、イギリス、CF14 4XW
- 募集
- University Hospital of Wales
-
コンタクト：
- Timothy Maughan, MD
- 電話番号：44-2920-316-904
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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* or radiologically confirmed primary adenocarcinoma of the colon or rectum
- Advanced and/or metastatic disease NOTE: *Liver metastases should not be biopsied
Must have potentially resectable liver metastases present, as defined by any of the following:
- Metachronous metastases AND complete resection of the primary tumor without gross or microscopic evidence of residual disease (R0)
- Synchronous metastases AND R0 resection of the primary tumor > 1 month before study entry
- Synchronous metastases with sufficient evidence (e.g., by CT scan or diagnostic laparoscopy) that both the primary tumor and the liver metastases can be completely resected during the same procedure and resection of primary tumor can be delayed for 3-4 months
- Suboptimally resectable disease (i.e., potentially resectable disease with compromise of the resection margins)
- No detectable extrahepatic tumor that cannot be completely resected
- Unidimensionally measurable disease
- No brain metastases
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- WBC ≥ 4,000/mm³
- ANC ≥ 1,500/mm³
- Platelet count > 150,000/mm³
- Bilirubin ≤ 1.25 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 5 times ULN
- AST or ALT ≤ 3 times ULN
- Creatinine clearance > 50 mL/min OR glomerular filtration rate > 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
- No psychiatric or neurological condition that would preclude study compliance
- No partial or complete bowel obstruction
- No preexisting neuropathy > grade 1
- No other prior or concurrent malignant disease that, in the opinion of the investigator, would preclude study treatment
- No concurrent severe uncontrolled medical illness (including poorly-controlled angina or myocardial infarction within the past 3 months) that would preclude study treatment
- No known hypersensitivity reaction to any of the components of the study drugs
PRIOR CONCURRENT THERAPY:
- No prior systemic chemotherapy for metastatic disease
- More than 6 months since prior adjuvant chemotherapy comprising fluorouracil, leucovorin calcium, capecitabine, or irinotecan hydrochloride
- More than 1 month since prior rectal chemoradiotherapy comprising fluorouracil and leucovorin calcium
- No concurrent contraindicated medication
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：OxMdG / IrMdG chemotherapy
OxMdG / IrMdG chemotherapy for 12 weeks Followed by surgery OxMdG / IrMdG chemotherapy for 12 weeks
|
|
|
実験的：OxMdG / IrMdG chemotherapy with cetuximab
OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks Followed by Surgery OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks
|
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 |
|---|---|
|
Progression-free survival
時間枠：end of study
|
end of study
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
全生存
時間枠：勉強の終わり
|
勉強の終わり
|
|
Response rate before surgery as assessed by RECIST criteria
時間枠：end of study
|
end of study
|
|
Pathological resection status
時間枠：end of study
|
end of study
|
|
Toxicity
時間枠：end of study
|
end of study
|
|
Quality of life as assessed by the EQ-5D, EORTC QLQ-C30, and EORTC QLQ-LMC21
時間枠：end of study
|
end of study
|
|
Cost effectiveness
時間枠：end of study
|
end of study
|
|
Safety
時間枠：end of study
|
end of study
|
協力者と研究者
捜査官
- スタディチェア：John N. Primrose, MD、University Hospital Southampton NHS Foundation Trust
研究記録日
主要日程の研究
研究開始
一次修了 (予想される)
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 (見積もり)
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
- CDR0000549541
- USCTU-4351
- USCTU-EPOC
- EUDRACT-2006-003121-82
- ISRCTN22944367
- EU-20732
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。