Combination Chemotherapy and Bevacizumab as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer (TRIBE)
2015年3月10日 更新者：Gruppo Oncologico del Nord-Ovest
A PHASE III RANDOMIZED TRIAL OF FOLFOXIRI + BEVACIZUMAB VERSUS FOLFIRI + BEVACIZUMAB AS FIRST- LINE TREATMENT FOR METASTATIC COLORECTAL CANCER
RATIONALE: Drugs used in chemotherapy, such as irinotecan, oxaliplatin, leucovorin, and fluorouracil, 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 bevacizumab, 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 bevacizumab may kill more tumor cells.
PURPOSE: This randomized phase III trial is comparing two combination chemotherapy regimens given together with bevacizumab to see how well they work as first-line therapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.
調査の概要
詳細な説明
OBJECTIVES:
Primary
- To compare the progression-free survival of bevacizumab in combination with oxaliplatin, irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFOXIRI) versus bevacizumab in combination with irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFIRI) in patients with unresectable, metastatic colorectal cancer.
Secondary
- To evaluate the safety profile, including long-term adverse events of these regimens in these patients.
- To compare the overall response rate, duration of response, and secondary R0 surgery rates of metastases and overall survival between treatment arms.
- To evaluate potential surrogate markers predictive of bevacizumab activity.
OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status (0 vs 1-2), prior adjuvant chemotherapy (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms.
- Arm I (FOLFOXIRI): Patients receive irinotecan hydrochloride IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1.
- Arm II (FOLFIRI): Patients receive irinotecan hydrochloride IV over 1 hour, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1.
In both arms, treatment repeats every 2 weeks for up to 12 courses. Treatment with bevacizumab, fluorouracil, and leucovorin calcium continues in the absence of disease progression or unacceptable toxicity.
Patients undergo serum extraction and blood sample collection periodically for genotyping studies. Patients also undergo collection of tumoral sections from paraffin embedded primary and/or metastatic lesions periodically for immunohistochemical analyses.
After completion of study treatment, patients are followed every 8 weeks.
研究の種類
介入
入学 (実際)
509
段階
- フェーズ 3
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Alessandria、イタリア、15100
- Ospedale Civile Ss. Antonio E Biagio Di Alessandria - Alessandria (Al) Oncologia Medica
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Ancona、イタリア、60100
- A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona - Ancona (An) Oncologia Medica
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Arezzo、イタリア、52100
- P.O. Zona Aretina - Ospedale S. Donato Di Arezzo - Arezzo (Ar) Oncologia Medica
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Aviano、イタリア、33081
- Irccs Centro Di Riferimento Oncologico (Cro) - Aviano (Pn) Oncologia Medica
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Brescia、イタリア、25122
- Ospedale S. Orsola F.B.F. - Brescia - Brescia (Bs) Oncologia Medica
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Brescia、イタリア、25124
- Istituto Ospedaliero Fondazione Poliambulanza Di Brescia - Brescia (Bs) Oncologia Medica
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Brindisi、イタリア、72100
- Stabilimento "Perrino" - Brindisi - Brindisi (Br) Oncologia Medica
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Caltanissetta、イタリア、93100
- Azienda Ospedaliera S. Elia - Caltanissetta (Cl) Oncologia Medica
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Carrara、イタリア、54033
- Ausl 1 Di Massa E Carrara - Carrara (Ms) Oncologia Medica
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Cecina、イタリア、57023
- Ospedale Cecina - Cecina (Li) Oncologia Medica
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Cremona、イタリア、26100
- Istituti Ospitalieri - Cremona - Cremona (Cr) Oncologia Medica
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Cuneo、イタリア、12100
- Azienda Ospedaliera S. Croce E Carle Di Cuneo - Cuneo (Cn) Oncoematologia
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Empoli、イタリア、50053
- Ausl 11 Di Empoli (Fi) - Empoli (Fi) Oncologia Medica
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Fabriano、イタリア、60044
- U.S.L.N.6 -Ospedale Civile 'E.Profili'-F - Fabriano (An) Oncologia Medica
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Firenze、イタリア、50122
- Ausl 10 Di Firenze - Firenze (Fi) Oncologia Medica
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Genova、イタリア、16132
- Irccs Istituto Nazionale Per La Ricerca Sul Cancro (Ist) - Genova (Ge) Oncologia Medica
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Lecce、イタリア、73100
- Ausl Le Di Lecce - Lecce (Le) Oncologia Medica
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Legnano、イタリア、37045
- Aulss 21 Di Legnago (Vr) - Legnago (Vr) Oncologia Medica
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Lido di Camaiore、イタリア、55053
- Ausl 12 Di Viareggio (Lu) - Lido Di Camaiore (Lu) Oncologia Medica
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Livorno、イタリア、57100
- Ospedale Livorno - Livorno (Li), Oncologia Medica
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Lucca、イタリア、25124
- Presidio Ospedaliero Piana Di Lucca - Lucca (Lu) Oncologia Medica
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Milano、イタリア、20132
- Irccs Fondazione Centro S. Raffaele Del Monte Tabor - Milano (Mi) Oncologia Medica
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Milano、イタリア、20162
- Ospedale Ca' Granda-Niguarda - Milano - Milano (Mi) Oncologia Medica
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Monza、イタリア、20052
- S.Gerardo - Monza - Monza (Mi) Oncologia Medica
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Napoli、イタリア、80131
- A.O. Universitaria Federico Ii Di Napoli Oncologia Medica
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Novara、イタリア、28100
- A.O. Universitaria Maggiore Della Carita' Di Novara Oncologia Medica
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Parma、イタリア、43100
- A.O. Universitaria Di Parma Oncologia Medica
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Perugia、イタリア、06012
- Asl 1 Di Citta' Di Castello (Pg) - Citta' Di Castello (Pg) Oncologia Medica
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Perugia、イタリア、06156
- A.O. Di Perugia - Ospedale S. Maria Della Misericordia (Ex Silvestrini) - Perugia (Pg) Oncologia Medica
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Pesaro、イタリア、61100
- Azienda Ospedaliera San Salvatore - Pesaro (Pu) Oncologia Medica
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Pescia、イタリア、51017
- Ospedale Della Valdinievole - Pescia (Pt) Oncologia Medica
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Piombino、イタリア、57100
- Ospedale Piombino - Piombino (Li) Oncologia Medica
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Pisa、イタリア、56100
- Ausl 5 Di Pisa - Pisa (Pi) Oncologia Medica
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Pisa、イタリア、56100
- A.O. Universitaria Pisana Oncologia Medica
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Pisa、イタリア、56126
- Alfredo Falcone A.O. Universitaria Pisana - Pisa (Pi) Oncologia Medica
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Pistoia、イタリア、51100
- Ausl 3 Di Pistoia - Pistoia (Pt) Oncologia Medica
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Prato、イタリア、59100
- Ausl 4 Di Prato - Prato (Po) Oncologia Medica
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Reggio Emilia、イタリア、42100
- Ospedale Di S. Maria Nuova - Reggio Nell'Emilia (Re) Oncologia Medica
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Rome、イタリア、00155
- Policlinico Universitario Campus Bio-Medico Di Roma Oncologia Medica
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Rome、イタリア、00161
- Policlinico Umberto I Di Roma Oncologia Medica
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Rome、イタリア、00168
- Policlinico Universitario Gemelli Di Roma Oncologia Medica
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Siena、イタリア、53100
- A.O. Universitaria Senese Oncologia Medica
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Sondrio、イタリア、23100
- Ospedale Civile - Sondrio - Sondrio (So) Oncologia Medica
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Torino、イタリア、10134
- A.O. Universitaria S. Giovanni Battista-Molinette Di Torino Oncologia Medica
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年～75年 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
DISEASE CHARACTERISTICS:
Histologically confirmed colorectal cancer
- Unresectable metastatic disease
- Measurable disease, defined as ≥ 1 measurable lesion according to RECIST criteria
- No prior chemotherapy for metastatic disease
- No untreated brain metastases, spinal cord compression, or primary brain tumors
- No history or evidence of CNS disease by physical examination unless adequately treated (e.g., uncontrolled seizure despite standard medical therapy or history of stroke)
PATIENT CHARACTERISTICS:
Inclusion criteria:
- ECOG performance status (PS) 0-2 (≤ 70 years of age) OR ECOG PS 0 (71-75 years of age)
- Life expectancy ≥ 12 weeks
- Neutrophils ≥ 1.5 x 10^9/L
- Platelet count ≥ 100 x 10^9/L
- Hemoglobin > 9 g/dL
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN if f liver metastases present)
- Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN if liver metastases present)
- Creatinine clearance > 50 mL/min OR serum creatinine ≤ 1.5 times ULN
- Proteinuria < 2+ by dipstick OR urine protein ≤ 1 g by 24-hr urine collection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
Exclusion criteria:
- Serious, nonhealing wound, ulcer, or bone fracture
- Evidence of bleeding diathesis or coagulopathy
- Uncontrolled hypertension
Clinically significant (i.e., active) cardiovascular disease, including any of the following:
- Cerebrovascular accidents within the past 6 months
- Myocardial infarction within the past 6 months
- Unstable angina
- New York Heart Association class II-IV congestive heart failure
- Serious cardiac arrhythmia requiring medication
- Known allergy to Chinese hamster ovary cell proteins or any of the components of the study medications
- Other co-existing malignancy or malignancy diagnosed within the past 5 years, except for basal cell or squamous cell carcinoma, or carcinoma in situ of the cervix
- Symptomatic peripheral neuropathy ≥ grade 1 according to the NCI Common Toxicity Criteria
- Lack of physical integrity of the upper gastrointestinal tract
- Malabsorption syndrome
- Inability to take oral medication
- Significant traumatic injury within the past 28 days
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- More than 4 weeks since prior radiotherapy
- More than 10 days since prior and no concurrent ongoing treatment with anticoagulants for therapeutic purposes
- More than 28 days since prior and no concurrent major surgical procedure
- More than 28 days since prior open biopsy
- More than 30 days since prior investigational agents
- No concurrent chronic daily high-dose acetylsalicylic acid (> 325 mg/day)
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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 |
|---|---|
|
実験的：Arm I (FOLFOXIRI)
Patients receive irinotecan hydrochloride IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1.
Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1.
|
与えられた IV
与えられた IV
与えられた IV
与えられた IV
与えられた IV
|
|
実験的：Arm II (FOLFIRI)
Patients receive irinotecan hydrochloride IV over 1 hour, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1.
Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1.
|
与えられた IV
与えられた IV
与えられた IV
与えられた IV
|
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 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Progression free survival
時間枠：up to 54 months
|
To compare the progression free survival of bevacizumab in combination with oxaliplatin, irinotecan and infusional 5FU/LV ("GONO" FOLFOXIRI regimen) to bevacizumab in combination with irinotecan and infusional 5FU/LV (FOLFIRI regimen)
|
up to 54 months
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
Overall response rate
時間枠：up to 54 months
|
up to 54 months
|
|
Duration of response
時間枠：up to 54 months
|
up to 54 months
|
|
Secondary R0 surgery rates of metastases
時間枠：up to 54 months
|
up to 54 months
|
|
Overall survival
時間枠：up to 54 months
|
up to 54 months
|
|
Surrogate markers predictive of bevacizumab activity
時間枠：up to 54 months
|
up to 54 months
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者：Alfredo Falcone, MD、Presidio Ospedaliero Di Livorno
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Tokunaga R, Cao S, Naseem M, Lo JH, Battaglin F, Puccini A, Berger MD, Soni S, Millstein J, Zhang W, Stintzing S, Loupakis F, Cremolini C, Heinemann V, Falcone A, Lenz HJ. Prognostic Effect of Adenosine-related Genetic Variants in Metastatic Colorectal Cancer Treated With Bevacizumab-based Chemotherapy. Clin Colorectal Cancer. 2019 Mar;18(1):e8-e19. doi: 10.1016/j.clcc.2018.09.003. Epub 2018 Sep 13.
- Cremolini C, Loupakis F, Masi G, Lonardi S, Granetto C, Mancini ML, Chiara S, Moretto R, Rossini D, Vitello S, Allegrini G, Tonini G, Bergamo F, Tomasello G, Ronzoni M, Buonadonna A, Bustreo S, Barbara C, Boni L, Falcone A. FOLFOXIRI or FOLFOXIRI plus bevacizumab as first-line treatment of metastatic colorectal cancer: a propensity score-adjusted analysis from two randomized clinical trials. Ann Oncol. 2016 May;27(5):843-9. doi: 10.1093/annonc/mdw052. Epub 2016 Feb 9.
- Cremolini C, Antoniotti C, Stein A, Bendell J, Gruenberger T, Rossini D, Masi G, Ongaro E, Hurwitz H, Falcone A, Schmoll HJ, Di Maio M. Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer. J Clin Oncol. 2020 Aug 20:JCO2001225. doi: 10.1200/JCO.20.01225. Online ahead of print.
- Rossini D, Germani MM, Lonardi S, Pietrantonio F, Dell'Aquila E, Borelli B, Allegrini G, Maddalena G, Randon G, Marmorino F, Zaniboni A, Buonadonna A, Boccaccino A, Conca V, Antoniotti C, Passardi A, Masi G, Cremolini C. Treatments after second progression in metastatic colorectal cancer: A pooled analysis of the TRIBE and TRIBE2 studies. Eur J Cancer. 2022 Jul;170:64-72. doi: 10.1016/j.ejca.2022.04.019. Epub 2022 May 17.
- Antoniotti C, Germani MM, Rossini D, Lonardi S, Pietrantonio F, Santini D, Marmorino F, Allegrini G, Daniel F, Raimondi A, Borelli B, Zaniboni A, Conca V, Abraham J, Spetzler D, Maiello E, Boccaccino A, Passardi A, Giordano M, Tamburini E, Korn MW, Masi G, Cremolini C. FOLFOXIRI and bevacizumab in patients with early-onset metastatic colorectal cancer. A pooled analysis of TRIBE and TRIBE2 studies. Eur J Cancer. 2022 May;167:23-31. doi: 10.1016/j.ejca.2022.02.031. Epub 2022 Mar 30.
- Cremolini C, Antoniotti C, Lonardi S, Bergamo F, Cortesi E, Tomasello G, Moretto R, Ronzoni M, Racca P, Loupakis F, Zaniboni A, Tonini G, Buonadonna A, Marmorino F, Allegrini G, Granetto C, Masi G, Zagonel V, Sensi E, Fontanini G, Boni L, Falcone A. Primary tumor sidedness and benefit from FOLFOXIRI plus bevacizumab as initial therapy for metastatic colorectal cancer. Retrospective analysis of the TRIBE trial by GONO. Ann Oncol. 2018 Jul;29(7):1528-1534. doi: 10.1093/annonc/mdy140. Epub 2018 Apr 20.
- Cremolini C, Del Re M, Antoniotti C, Lonardi S, Bergamo F, Loupakis F, Borelli B, Marmorino F, Citi V, Cortesi E, Moretto R, Ronzoni M, Tomasello G, Zaniboni A, Racca P, Buonadonna A, Allegrini G, Ricci V, Di Donato S, Zagonel V, Boni L, Falcone A, Danesi R. DPYD and UGT1A1 genotyping to predict adverse events during first-line FOLFIRI or FOLFOXIRI plus bevacizumab in metastatic colorectal cancer. Oncotarget. 2017 Dec 21;9(8):7859-7866. doi: 10.18632/oncotarget.23559. eCollection 2018 Jan 30.
- Cremolini C, Casagrande M, Loupakis F, Aprile G, Bergamo F, Masi G, Moretto R R, Pietrantonio F, Marmorino F, Zucchelli G, Tomasello G, Tonini G, Allegrini G, Granetto C, Ferrari L, Urbani L, Cillo U, Pilati P, Sensi E, Pellegrinelli A, Milione M, Fontanini G, Falcone A. Efficacy of FOLFOXIRI plus bevacizumab in liver-limited metastatic colorectal cancer: A pooled analysis of clinical studies by Gruppo Oncologico del Nord Ovest. Eur J Cancer. 2017 Mar;73:74-84. doi: 10.1016/j.ejca.2016.10.028. Epub 2016 Dec 13.
- Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, Mezi S, Tomasello G, Ronzoni M, Zaniboni A, Tonini G, Carlomagno C, Allegrini G, Chiara S, D'Amico M, Granetto C, Cazzaniga M, Boni L, Fontanini G, Falcone A. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015 Oct;16(13):1306-15. doi: 10.1016/S1470-2045(15)00122-9. Epub 2015 Aug 31.
- Cremolini C, Loupakis F, Antoniotti C, Lonardi S, Masi G, Salvatore L, Cortesi E, Tomasello G, Spadi R, Zaniboni A, Tonini G, Barone C, Vitello S, Longarini R, Bonetti A, D'Amico M, Di Donato S, Granetto C, Boni L, Falcone A. Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest. Ann Oncol. 2015 Jun;26(6):1188-1194. doi: 10.1093/annonc/mdv112. Epub 2015 Feb 23.
- Loupakis F, Cremolini C, Masi G, Lonardi S, Zagonel V, Salvatore L, Cortesi E, Tomasello G, Ronzoni M, Spadi R, Zaniboni A, Tonini G, Buonadonna A, Amoroso D, Chiara S, Carlomagno C, Boni C, Allegrini G, Boni L, Falcone A. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014 Oct 23;371(17):1609-18. doi: 10.1056/NEJMoa1403108.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2008年7月1日
一次修了 (実際)
2011年5月1日
試験登録日
最初に提出
2008年7月19日
QC基準を満たした最初の提出物
2008年7月19日
最初の投稿 (見積もり)
2008年7月22日
学習記録の更新
投稿された最後の更新 (見積もり)
2015年3月11日
QC基準を満たした最後の更新が送信されました
2015年3月10日
最終確認日
2015年3月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- CDR0000598582
- GONO-TRIBE
- ASL608LIOM04
- EUDRACT:2008-001537-10
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。