A Study Combining mFOLFOX6 With Tivozanib or Bevacizumab in Patients With Metastatic Colorectal Cancer as First Line Therapy
A Phase 2, Open Label, Multicenter, Randomized Trial Comparing Tivozanib in Combination With mFOLFOX6 to Bevacizumab in Combination With mFOLFOX6, In Stage IV Metastatic Colorectal Cancer (mCRC) Subjects
2 other identifiers
interventional
265
11 countries
65
Brief Summary
The objective of this study is to compare the progression free survival (PFS), overall survival (OS), objective response rate (ORR), time to treatment failure (TTF), duration of response (DoR), quality of life, safety and tolerability of tivozanib in combination with mFOLFOX6 and bevacizumab in combination with mFOLFOX6.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 colorectal-cancer
Started Dec 2011
65 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 21, 2011
CompletedFirst Posted
Study publicly available on registry
November 23, 2011
CompletedStudy Start
First participant enrolled
December 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2015
CompletedResults Posted
Study results publicly available
April 3, 2015
CompletedJuly 8, 2015
June 1, 2015
1.8 years
November 21, 2011
February 19, 2015
June 9, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Investigator-assessed Progression-Free Survival (PFS)
The time from the date of randomization until objective tumor progression or death due to any cause. Objective tumor progression was determined through radiological imaging and based on the requirements of the Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1): Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of existing non-target lesions or the appearance of one or more new lesions. Participants who did not progress or had not died at the time of the analysis were censored at the date of last tumor assessment where non-progression was documented.
From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group.
Secondary Outcomes (20)
Progression-Free Survival (PFS) Based on Independent Radiological Review (IRR)
3 years
Overall Survival (OS)
From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group.
Objective Response Rate (ORR)
From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group.
Duration of Response (DoR)
From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group.
Time to Treatment Failure (TTF)
From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group.
- +15 more secondary outcomes
Study Arms (2)
Tivozanib + mFOLFOX6
EXPERIMENTALParticipants received 1.5 mg of tivozanib orally once daily beginning on Day 1 of each cycle for 21 days followed by 7 days off treatment. Participants also received modified FOLFOX6 (mFOLFOX6) chemotherapy every 2 weeks on Days 1 and 15 of each cycle.
Bevacizumab + mFOLFOX6
ACTIVE COMPARATORParticipants received a dose of 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle. Participants also received mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle.
Interventions
mFOLFOX6 regimen is a combination therapy of oxaliplatin 85 mg/m\^2 administered as an intravenous bolus over 2 hours on Days 1 and 15, leucovorin calcium 400 mg/m\^2 administered as an intravenous bolus over 2 hours on Days 1 and 15, fluorouracil 400 mg/m\^2 administered as an intravenous bolus over 5 to 15 minutes on Days 1 and 15, then 2400 mg/m\^2 continuous intravenous infusion over 46 hours on Days 1 to 3 and 15 to 17.
Eligibility Criteria
You may qualify if:
- Documented diagnosis of metastatic colorectal cancer
- One measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- No prior systemic chemotherapy for advanced colorectal cancer; no fluorouracil containing adjuvant therapy in previous 6 months
- Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
You may not qualify if:
- Any prior Vascular Endothelial Growth Factor (VEGF)-directed therapy or any other agent or investigational agent targeting the VEGF pathway
- Primary Central Nervous System (CNS) malignancies or CNS metastases
- Hematologic abnormalities:
- Hemoglobin \< 9.0 g/dL,
- Absolute neutrophil count (ANC) \< 2000 per mm\^3,
- Platelet count \< 100,000 per mm\^3,
- Prothrombin (PT) or Partial Thromboplastin Time (PTT) \> 1.5 X Upper Limit of Normal (ULN)
- Serum chemistry abnormalities:
- Total bilirubin \> 1.5 X ULN,
- Aspartate aminotransferase (AST) or Alanine Aminotransferase (ALT) \> 2.5 X ULN,
- Alkaline phosphatase \> 2.5 X ULN,
- Serum albumin \< 2.0 g/dL,
- Creatinine \> 1.5 X ULN,
- Proteinuria \> 2+ by urine dipstick
- Significant cardiovascular disease
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (73)
Banner MD Anderson Cancer Research Center
Gilbert, Arizona, 85234, United States
Genesis Cancer Center
Hot Springs, Arizona, 71913, United States
Arizona Clinical Research Center
Tucson, Arizona, 85715, United States
University of California San Diego-Morris Cancer Center
La Jolla, California, 92093, United States
UC Irvine Medical Center, Division of Hematology/Oncology
Orange, California, 92868, United States
Desert Hematology Oncology Medical Group, Inc.
Rancho Mirage, California, 92270, United States
Mountain Blue Cancer Care Center
Golden, Colorado, 80033, United States
University of Florida, Davis Cancer Center (VA)
Gainesville, Florida, 32610, United States
Cleveland Clinic Florida
Weston, Florida, 33331, United States
Queen's Medical Center
Honolulu, Hawaii, 96813, United States
University of Hawaii
Honolulu, Hawaii, 96813, United States
Kaiser Foundation Hospitals
Honolulu, Hawaii, 96819, United States
Northwestern University
Chicago, Illinois, 60611, United States
Illinios Cancer Care
Peoria, Illinois, 61615, United States
Investigative Clinical Research of Indiana, LLC
Indianapolis, Indiana, 46260, United States
Horizon Oncology Research, Inc.
Lafayette, Indiana, 47905, United States
Associates of Oncology Hematology, P.C.
Rockville, Maryland, 20850, United States
University of Michigan Health
Ann Arbor, Michigan, 48109, United States
NYU Cancer Institute
New York, New York, 10016, United States
Alamance Regional Medical Center
Burlington, North Carolina, 27215, United States
Tri Country Hematology / Oncology
Canton, Ohio, 44718, United States
Signal Point Clinical Research Center, LLC
Middletown, Ohio, 45042, United States
Cancer Care Associates
Tulsa, Oklahoma, 74136, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Oncology Hematology of Lehigh Valley
Bethlehem, Pennsylvania, 18015, United States
Northern Utah Associates
Ogden, Utah, 84403, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
St George Hospital
Kogarah, New South Wales, 2217, Australia
Tweed Hospital
Tweed Heads, New South Wales, 2485, Australia
Calvary Mater Newcastle
Waratah, New South Wales, 2298, Australia
Flinders Medical Centre
Bedford Park, South Australia, 5042, Australia
Royal Hobart Hospital
Hobart, Tasmania, 7000, Australia
Ballarat Health Services
Ballarat, Victoria, 3350, Australia
Cabrini Hospital Malvern
Malvern, Victoria, 3144, Australia
Border Medical Oncology
Wodonga, Victoria, 3690, Australia
Medizinische Universitat Graz
Graz, 8036, Austria
Salzburger Landesklinken
Salzburg, 5020, Austria
Klinikum Wels-Grieskirchen GmbH
Wels, 4600, Austria
Ziekenhuisnetwerk Antwerpen - AZ Middelheim
Antwerp, 2020, Belgium
Imelda VZW
Bonheiden, 2820, Belgium
AZ Sint-Lucas Brugge
Bruges, 8310, Belgium
AZ Groeninge - Campus Sint-Niklaas
Kortrijk, 8500, Belgium
British Columbia Cancer Agency
Vancouver, British Columbia, V5Z 4E6, Canada
QEII Health Science Centre
Halifax, Nova Scotia, B3H 2Y9, Canada
Hopital De La Cite-De-La-Sante
Laval, Quebec, H7M 3L9, Canada
Hopital Saint-Luc - Pavillon Principal
Montreal, Quebec, H2X 3J4, Canada
Chuq Centre Hospitalier Universitaire De Quebec
Québec, Quebec, G1R 2J6, Canada
Masarykuv onkologicky ustav
Brno, 656 53, Czechia
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05, Czechia
Tampereen yliopistollinen sairaala
Tampere, FI-33520, Finland
Turun yliopistollinen keskussairaala
Turku, FI-20520, Finland
Orszagos Onkologiai Intezet
Budapest, 1122, Hungary
Petz Aladar Megyei Oktato Korhaz
Győr, 9024, Hungary
Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza
Gyula, 5700, Hungary
Fejer Megyei Szent Gyorgy Korhaz
Székesfehérvár, 8000, Hungary
Azienda Ospedaliero- Universitaria di Bologna - Policlinico S.Orsola-Malpighi
Bologna, 40128, Italy
Fondazione del Piemonte per I'Oncologia IRCC
Candiolo, 10060, Italy
IRCCS Azienda Ospedaliera Universitaria San Martino - Istituto Nazionale per la Ricerca sul Cancro
Genova, 16132, Italy
Istituto Clinico Humanitas
Rozzano (MI), 20089, Italy
Amphia Ziekenhuis
Breda, 4819 EV, Netherlands
Hospital Universitario Miguel Servet
Zaragoza, Aragon, 50009, Spain
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, 39008, Spain
Corporacio Sanitaria Parc Tauli
Sabadell, Catalonia, 08208, Spain
Hospital Mutua de Terrassa
Terrassa, Catalonia, 08221, Spain
Centro Oncologico de Galicia
Galicia, 15009, Spain
Centro Integral Oncologico Clara Campal
Madrid, 28050, Spain
Addenbrooke's Hospital
Cambridge, CB2 2QQ, United Kingdom
Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
Beatson West of Scotland Cancer Center
Glasgow, G12 0YN, United Kingdom
University College Hospital
London, NW1 2BU, United Kingdom
Maidstone Hospital
Maidstone, ME16 9QQ, United Kingdom
Christie Hospital
Manchester, M20 4BX, United Kingdom
Peterborough and Stamford Hospitals NHS Foundation Trust
Peterborough, PE3 6DA, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Director
- Organization
- AVEO
Study Officials
- STUDY DIRECTOR
Medical Director
AVEO Pharmaceuticals, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 21, 2011
First Posted
November 23, 2011
Study Start
December 1, 2011
Primary Completion
September 1, 2013
Study Completion
January 1, 2015
Last Updated
July 8, 2015
Results First Posted
April 3, 2015
Record last verified: 2015-06