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.
研究概览
详细说明
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.
研究类型
介入性
注册 (实际的)
509
阶段
- 第三阶段
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Alessandria、意大利、15100
- Ospedale Civile Ss. Antonio E Biagio Di Alessandria - Alessandria (Al) Oncologia Medica
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Ancona、意大利、60100
- A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona - Ancona (An) Oncologia Medica
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Arezzo、意大利、52100
- P.O. Zona Aretina - Ospedale S. Donato Di Arezzo - Arezzo (Ar) Oncologia Medica
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Aviano、意大利、33081
- Irccs Centro Di Riferimento Oncologico (Cro) - Aviano (Pn) Oncologia Medica
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Brescia、意大利、25122
- Ospedale S. Orsola F.B.F. - Brescia - Brescia (Bs) Oncologia Medica
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Brescia、意大利、25124
- Istituto Ospedaliero Fondazione Poliambulanza Di Brescia - Brescia (Bs) Oncologia Medica
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Brindisi、意大利、72100
- Stabilimento "Perrino" - Brindisi - Brindisi (Br) Oncologia Medica
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Caltanissetta、意大利、93100
- Azienda Ospedaliera S. Elia - Caltanissetta (Cl) Oncologia Medica
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Carrara、意大利、54033
- Ausl 1 Di Massa E Carrara - Carrara (Ms) Oncologia Medica
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Cecina、意大利、57023
- Ospedale Cecina - Cecina (Li) Oncologia Medica
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Cremona、意大利、26100
- Istituti Ospitalieri - Cremona - Cremona (Cr) Oncologia Medica
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Cuneo、意大利、12100
- Azienda Ospedaliera S. Croce E Carle Di Cuneo - Cuneo (Cn) Oncoematologia
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Empoli、意大利、50053
- Ausl 11 Di Empoli (Fi) - Empoli (Fi) Oncologia Medica
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Fabriano、意大利、60044
- U.S.L.N.6 -Ospedale Civile 'E.Profili'-F - Fabriano (An) Oncologia Medica
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Firenze、意大利、50122
- Ausl 10 Di Firenze - Firenze (Fi) Oncologia Medica
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Genova、意大利、16132
- Irccs Istituto Nazionale Per La Ricerca Sul Cancro (Ist) - Genova (Ge) Oncologia Medica
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Lecce、意大利、73100
- Ausl Le Di Lecce - Lecce (Le) Oncologia Medica
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Legnano、意大利、37045
- Aulss 21 Di Legnago (Vr) - Legnago (Vr) Oncologia Medica
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Lido di Camaiore、意大利、55053
- Ausl 12 Di Viareggio (Lu) - Lido Di Camaiore (Lu) Oncologia Medica
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Livorno、意大利、57100
- Ospedale Livorno - Livorno (Li), Oncologia Medica
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Lucca、意大利、25124
- Presidio Ospedaliero Piana Di Lucca - Lucca (Lu) Oncologia Medica
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Milano、意大利、20132
- Irccs Fondazione Centro S. Raffaele Del Monte Tabor - Milano (Mi) Oncologia Medica
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Milano、意大利、20162
- Ospedale Ca' Granda-Niguarda - Milano - Milano (Mi) Oncologia Medica
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Monza、意大利、20052
- S.Gerardo - Monza - Monza (Mi) Oncologia Medica
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Napoli、意大利、80131
- A.O. Universitaria Federico Ii Di Napoli Oncologia Medica
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Novara、意大利、28100
- A.O. Universitaria Maggiore Della Carita' Di Novara Oncologia Medica
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Parma、意大利、43100
- A.O. Universitaria Di Parma Oncologia Medica
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Perugia、意大利、06012
- Asl 1 Di Citta' Di Castello (Pg) - Citta' Di Castello (Pg) Oncologia Medica
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Perugia、意大利、06156
- A.O. Di Perugia - Ospedale S. Maria Della Misericordia (Ex Silvestrini) - Perugia (Pg) Oncologia Medica
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Pesaro、意大利、61100
- Azienda Ospedaliera San Salvatore - Pesaro (Pu) Oncologia Medica
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Pescia、意大利、51017
- Ospedale Della Valdinievole - Pescia (Pt) Oncologia Medica
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Piombino、意大利、57100
- Ospedale Piombino - Piombino (Li) Oncologia Medica
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Pisa、意大利、56100
- Ausl 5 Di Pisa - Pisa (Pi) Oncologia Medica
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Pisa、意大利、56100
- A.O. Universitaria Pisana Oncologia Medica
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Pisa、意大利、56126
- Alfredo Falcone A.O. Universitaria Pisana - Pisa (Pi) Oncologia Medica
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Pistoia、意大利、51100
- Ausl 3 Di Pistoia - Pistoia (Pt) Oncologia Medica
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Prato、意大利、59100
- Ausl 4 Di Prato - Prato (Po) Oncologia Medica
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Reggio Emilia、意大利、42100
- Ospedale Di S. Maria Nuova - Reggio Nell'Emilia (Re) Oncologia Medica
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Rome、意大利、00155
- Policlinico Universitario Campus Bio-Medico Di Roma Oncologia Medica
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Rome、意大利、00161
- Policlinico Umberto I Di Roma Oncologia Medica
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Rome、意大利、00168
- Policlinico Universitario Gemelli Di Roma Oncologia Medica
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Siena、意大利、53100
- A.O. Universitaria Senese Oncologia Medica
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Sondrio、意大利、23100
- Ospedale Civile - Sondrio - Sondrio (So) Oncologia Medica
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Torino、意大利、10134
- A.O. Universitaria S. Giovanni Battista-Molinette Di Torino Oncologia Medica
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 75年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
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)
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：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.
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鉴于IV
鉴于IV
鉴于IV
鉴于IV
鉴于IV
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实验性的：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.
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鉴于IV
鉴于IV
鉴于IV
鉴于IV
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Progression free survival
大体时间：up to 54 months
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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
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次要结果测量
结果测量 |
大体时间 |
|---|---|
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Overall response rate
大体时间：up to 54 months
|
up to 54 months
|
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Duration of response
大体时间：up to 54 months
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up to 54 months
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Secondary R0 surgery rates of metastases
大体时间：up to 54 months
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up to 54 months
|
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Overall survival
大体时间：up to 54 months
|
up to 54 months
|
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Surrogate markers predictive of bevacizumab activity
大体时间：up to 54 months
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up to 54 months
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Alfredo Falcone, MD、Presidio Ospedaliero Di Livorno
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- 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.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2008年7月1日
初级完成 (实际的)
2011年5月1日
研究注册日期
首次提交
2008年7月19日
首先提交符合 QC 标准的
2008年7月19日
首次发布 (估计)
2008年7月22日
研究记录更新
最后更新发布 (估计)
2015年3月11日
上次提交的符合 QC 标准的更新
2015年3月10日
最后验证
2015年3月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- CDR0000598582
- GONO-TRIBE
- ASL608LIOM04
- EUDRACT:2008-001537-10
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.