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

This study has been completed.
Sponsor:
Information provided by:
Gruppo Oncologico del Nord-Ovest
ClinicalTrials.gov Identifier:
NCT00719797
First received: July 19, 2008
Last updated: October 12, 2012
Last verified: July 2009
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Biological: bevacizumab
Drug: fluorouracil
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Drug: oxaliplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE IIIIII RANDOMIIZED TRIIAL OF FOLFOXIIRII + BEVACIIZUMAB VERSUS FOLFIIRII + BEVACIIZUMAB AS FIIRST-- LIINE TREATMENT FOR METASTATIIC COLORECTAL CANCER

Resource links provided by NLM:


Further study details as provided by Gruppo Oncologico del Nord-Ovest:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: up to 54 months ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • Overall response rate [ Time Frame: up to 54 months ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: up to 54 months ] [ Designated as safety issue: No ]
  • Secondary R0 surgery rates of metastases [ Time Frame: up to 54 months ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: up to 54 months ] [ Designated as safety issue: No ]
  • Surrogate markers predictive of bevacizumab activity [ Time Frame: up to 54 months ] [ Designated as safety issue: No ]

Enrollment: 509
Study Start Date: July 2008
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: bevacizumab
Given IV
Drug: fluorouracil
Given IV
Drug: irinotecan hydrochloride
Given IV
Drug: leucovorin calcium
Given IV
Drug: oxaliplatin
Given IV
Experimental: 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.
Biological: bevacizumab
Given IV
Drug: fluorouracil
Given IV
Drug: irinotecan hydrochloride
Given IV
Drug: leucovorin calcium
Given IV

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00719797

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

Additional Information:
No publications provided by Gruppo Oncologico del Nord-Ovest

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00719797     History of Changes
Other Study ID Numbers: CDR0000598582, GONO-TRIBE, ASL608LIOM04, EUDRACT:2008-001537-10
Study First Received: July 19, 2008
Last Updated: October 12, 2012
Health Authority: Italy: Ethics Committee

Keywords provided by Gruppo Oncologico del Nord-Ovest:
stage IV rectal cancer
stage IV colon cancer
stage III rectal cancer
stage III colon cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Bevacizumab
Camptothecin
Fluorouracil
Irinotecan
Leucovorin
Levoleucovorin
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antidotes
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on November 24, 2014