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Combination Chemotherapy and Bevacizumab as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer (TRIBE)

10. marts 2015 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

509

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Italien
      • Alessandria, Italien, 15100
        • Ospedale Civile Ss. Antonio E Biagio Di Alessandria - Alessandria (Al) Oncologia Medica
      • Ancona, Italien, 60100
        • A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona - Ancona (An) Oncologia Medica
      • Arezzo, Italien, 52100
        • P.O. Zona Aretina - Ospedale S. Donato Di Arezzo - Arezzo (Ar) Oncologia Medica
      • Aviano, Italien, 33081
        • Irccs Centro Di Riferimento Oncologico (Cro) - Aviano (Pn) Oncologia Medica
      • Brescia, Italien, 25122
        • Ospedale S. Orsola F.B.F. - Brescia - Brescia (Bs) Oncologia Medica
      • Brescia, Italien, 25124
        • Istituto Ospedaliero Fondazione Poliambulanza Di Brescia - Brescia (Bs) Oncologia Medica
      • Brindisi, Italien, 72100
        • Stabilimento "Perrino" - Brindisi - Brindisi (Br) Oncologia Medica
      • Caltanissetta, Italien, 93100
        • Azienda Ospedaliera S. Elia - Caltanissetta (Cl) Oncologia Medica
      • Carrara, Italien, 54033
        • Ausl 1 Di Massa E Carrara - Carrara (Ms) Oncologia Medica
      • Cecina, Italien, 57023
        • Ospedale Cecina - Cecina (Li) Oncologia Medica
      • Cremona, Italien, 26100
        • Istituti Ospitalieri - Cremona - Cremona (Cr) Oncologia Medica
      • Cuneo, Italien, 12100
        • Azienda Ospedaliera S. Croce E Carle Di Cuneo - Cuneo (Cn) Oncoematologia
      • Empoli, Italien, 50053
        • Ausl 11 Di Empoli (Fi) - Empoli (Fi) Oncologia Medica
      • Fabriano, Italien, 60044
        • U.S.L.N.6 -Ospedale Civile 'E.Profili'-F - Fabriano (An) Oncologia Medica
      • Firenze, Italien, 50122
        • Ausl 10 Di Firenze - Firenze (Fi) Oncologia Medica
      • Genova, Italien, 16132
        • Irccs Istituto Nazionale Per La Ricerca Sul Cancro (Ist) - Genova (Ge) Oncologia Medica
      • Lecce, Italien, 73100
        • Ausl Le Di Lecce - Lecce (Le) Oncologia Medica
      • Legnano, Italien, 37045
        • Aulss 21 Di Legnago (Vr) - Legnago (Vr) Oncologia Medica
      • Lido di Camaiore, Italien, 55053
        • Ausl 12 Di Viareggio (Lu) - Lido Di Camaiore (Lu) Oncologia Medica
      • Livorno, Italien, 57100
        • Ospedale Livorno - Livorno (Li), Oncologia Medica
      • Lucca, Italien, 25124
        • Presidio Ospedaliero Piana Di Lucca - Lucca (Lu) Oncologia Medica
      • Milano, Italien, 20132
        • Irccs Fondazione Centro S. Raffaele Del Monte Tabor - Milano (Mi) Oncologia Medica
      • Milano, Italien, 20162
        • Ospedale Ca' Granda-Niguarda - Milano - Milano (Mi) Oncologia Medica
      • Monza, Italien, 20052
        • S.Gerardo - Monza - Monza (Mi) Oncologia Medica
      • Napoli, Italien, 80131
        • A.O. Universitaria Federico Ii Di Napoli Oncologia Medica
      • Novara, Italien, 28100
        • A.O. Universitaria Maggiore Della Carita' Di Novara Oncologia Medica
      • Parma, Italien, 43100
        • A.O. Universitaria Di Parma Oncologia Medica
      • Perugia, Italien, 06012
        • Asl 1 Di Citta' Di Castello (Pg) - Citta' Di Castello (Pg) Oncologia Medica
      • Perugia, Italien, 06156
        • A.O. Di Perugia - Ospedale S. Maria Della Misericordia (Ex Silvestrini) - Perugia (Pg) Oncologia Medica
      • Pesaro, Italien, 61100
        • Azienda Ospedaliera San Salvatore - Pesaro (Pu) Oncologia Medica
      • Pescia, Italien, 51017
        • Ospedale Della Valdinievole - Pescia (Pt) Oncologia Medica
      • Piombino, Italien, 57100
        • Ospedale Piombino - Piombino (Li) Oncologia Medica
      • Pisa, Italien, 56100
        • Ausl 5 Di Pisa - Pisa (Pi) Oncologia Medica
      • Pisa, Italien, 56100
        • A.O. Universitaria Pisana Oncologia Medica
      • Pisa, Italien, 56126
        • Alfredo Falcone A.O. Universitaria Pisana - Pisa (Pi) Oncologia Medica
      • Pistoia, Italien, 51100
        • Ausl 3 Di Pistoia - Pistoia (Pt) Oncologia Medica
      • Prato, Italien, 59100
        • Ausl 4 Di Prato - Prato (Po) Oncologia Medica
      • Reggio Emilia, Italien, 42100
        • Ospedale Di S. Maria Nuova - Reggio Nell'Emilia (Re) Oncologia Medica
      • Rome, Italien, 00155
        • Policlinico Universitario Campus Bio-Medico Di Roma Oncologia Medica
      • Rome, Italien, 00161
        • Policlinico Umberto I Di Roma Oncologia Medica
      • Rome, Italien, 00168
        • Policlinico Universitario Gemelli Di Roma Oncologia Medica
      • Siena, Italien, 53100
        • A.O. Universitaria Senese Oncologia Medica
      • Sondrio, Italien, 23100
        • Ospedale Civile - Sondrio - Sondrio (So) Oncologia Medica
      • Torino, Italien, 10134
        • A.O. Universitaria S. Giovanni Battista-Molinette Di Torino Oncologia Medica

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 75 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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)

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.
Biologisk: bevacizumab
Givet IV
Medicin: oxaliplatin
Givet IV
Medicin: leucovorin calcium
Givet IV
Medicin: fluorouracil
Givet IV
Medicin: irinotecan hydrochlorid
Givet IV
Eksperimentel: 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.
Biologisk: bevacizumab
Givet IV
Medicin: leucovorin calcium
Givet IV
Medicin: fluorouracil
Givet IV
Medicin: irinotecan hydrochlorid
Givet IV

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Progression free survival
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Tidsramme
Overall response rate
Tidsramme: up to 54 months
up to 54 months
Duration of response
Tidsramme: up to 54 months
up to 54 months
Secondary R0 surgery rates of metastases
Tidsramme: up to 54 months
up to 54 months
Overall survival
Tidsramme: up to 54 months
up to 54 months
Surrogate markers predictive of bevacizumab activity
Tidsramme: up to 54 months
up to 54 months

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Gruppo Oncologico del Nord-Ovest

Efterforskere

  • Ledende efterforsker: Alfredo Falcone, MD, Presidio Ospedaliero di Livorno

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. juli 2008

Primær færdiggørelse (Faktiske)

1. maj 2011

Datoer for studieregistrering

Først indsendt

19. juli 2008

Først indsendt, der opfyldte QC-kriterier

19. juli 2008

Først opslået (Skøn)

22. juli 2008

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

11. marts 2015

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

10. marts 2015

Sidst verificeret

1. marts 2015

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • CDR0000598582
  • GONO-TRIBE
  • ASL608LIOM04
  • EUDRACT:2008-001537-10

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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