Combination Chemotherapy and Bevacizumab as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer (TRIBE)
This study has been completed.
Sponsor:
Gruppo Oncologico del Nord-Ovest
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
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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:
Drug Information available for:
Fluorouracil
Calcium Gluconate
Leucovorin calcium
Oxaliplatin
Levoleucovorin
Irinotecan
Irinotecan hydrochloride
Bevacizumab
U.S. FDA Resources
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
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 | |
| Asl 1 Di Citta' Di Castello (Pg) - Citta' Di Castello (Pg) Oncologia Medica | |
| Perugia, Italy, 06012 | |
| A.O. Di Perugia - Ospedale S. Maria Della Misericordia (Ex Silvestrini) - Perugia (Pg) Oncologia Medica | |
| Perugia, Italy, 06156 | |
| 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 | |
| Ausl 5 Di Pisa - Pisa (Pi) Oncologia Medica | |
| Pisa, Italy, 56100 | |
| Alfredo Falcone A.O. Universitaria Pisana - Pisa (Pi) Oncologia Medica | |
| Pisa, Italy, 56126 | |
| A.O. Universitaria Pisana 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 Universitario Gemelli Di Roma Oncologia Medica | |
| Rome, Italy, 00168 | |
| Policlinico Universitario Campus Bio-Medico Di Roma Oncologia Medica | |
| Rome, Italy, 00155 | |
| Policlinico Umberto I Di Roma Oncologia Medica | |
| Rome, Italy, 00161 | |
| 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
| 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 Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Fluorouracil Oxaliplatin Irinotecan Bevacizumab |
Camptothecin Leucovorin Levoleucovorin Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antimetabolites, Antineoplastic Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Vitamin B Complex Vitamins Micronutrients |
ClinicalTrials.gov processed this record on May 23, 2013