A Study Combining mFOLFOX6 With Tivozanib or Bevacizumab in Patients With Metastatic Colorectal Cancer as First Line Therapy - Full Text View

Purpose

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.

Condition	Intervention	Phase
Colorectal Cancer	Drug: Tivozanib Drug: Bevacizumab Drug: mFOLFOX6	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Bevacizumab

U.S. FDA Resources

Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:

Progression-Free Survival (PFS) based on investigator radiological tumor assessment [ Time Frame: 3 years ] [ Designated as safety issue: No ]
The time from the date of randomization until objective tumor progression or death due to any cause. Objective tumor progression is defined by radiological assessments by the investigators.

Secondary Outcome Measures:

Progression-Free Survival (PFS) based on Independent Radiological Review (IRR) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
The time from the date of randomization until the date of radiological disease progression assessed by the IRR or until death due to any cause, even in the absence of radiological progression.
Overall survival (OS) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
The time from the date of randomization until death from any cause.
Objective Response Rate (ORR) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
The proportion of subjects with a confirmed complete response (CR ) or partial response (PR).
Duration of Response (DoR) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
The time from the date of the first documented radiological response (CR or PR) to the date of first documented radiological progression.
Time to Treatment Failure (TTF) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
The time from randomization to treatment discontinuation for any reason, including disease progression, toxicity, withdrawn consent, or death.
Health Related Quality of life (HRQoL) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Time to deterioration in HRQoL measured by Colorectal cancer (CRC) subscale of the Functional Assessment of cancer Therapy Colorectal (FACT-C) scale, change in score from baseline using the EQ-5D and Fact Colorectal Symptom Index (FCSI).
Safety as assessed by physical examination, vital signs, laboratory assessments, 12-lead electrocardiogram (ECGs), and adverse events [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Assessment of relationship of biomarker that may be predictive of level of response between 2 study arms: Biomarker Lactate Dehydrogenase ( LDH) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Assessment of relationship of biomarker that may be predictive of level of response between 2 study arms: Vascular Endothelial Growth Factor (VEGF-C,VEGF-D, VEGF-A) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Assessment of relationship of biomarker that may be predictive of relationship between 2 study arms: CD68 [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Assessment of relationship of biomarker that may be predictive of level of response between 2 study arms: myeloid-derived gene signature (MGS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Assessment of relationship of biomarker that may be predictive of level of response between 2 study arms: Serum soluble cytokines [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment:	265
Study Start Date:	November 2011
Estimated Study Completion Date:	December 2015
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm A: Tivozanib + mFOLFOX6	Drug: Tivozanib Oral and Intravenous Other Names: AV951 ASP4130 Drug: mFOLFOX6 Oxaliplatin, Leucovorin Calcium, Fluorouracil Bolus, Fluorouracil Infusion
Active Comparator: Arm B: Bevacizumab + mFOLFOX6	Drug: Bevacizumab Intravenous Other Name: Avastin Drug: mFOLFOX6 Oxaliplatin, Leucovorin Calcium, Fluorouracil Bolus, Fluorouracil Infusion

Detailed Description:

A 2:1 randomization between tivozanib in combination with mFOLFOX6 to bevacizumab in combination with mFOLFOX6. Subjects will be stratified by origin of cancer, Lactate Dehydrogenase (LDH) status, and number of metastatic sites.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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,
- ANC < 2000 per mm3,
- Platelet count < 100,000 per mm3,
- 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
Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug
Non-healing wound, bone fracture, or skin ulcer
Inadequate recovery from any prior surgical procedure or major surgical procedure within 8 weeks prior to administration, or anticipation of major surgical procedure during the course of the study
History of significant gastrointestinal (GI) toxicity, diarrhea, or stomatitis within the last 6 weeks
An active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug
Serious/active infection or infection requiring antibiotics
Significant bleeding disorders within 6 months prior to administration of first dose of study drug
Active second primary malignancy, other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer and ductal or lobular carcinoma in situ of the breast. Subject is not considered to have a currently active malignancy if they have completed anti-cancer therapy and have been disease free for > 5 years
History of allergic reactions, or intolerance, attributed to compounds of similar chemical or biologic composition to 5-fluorouracil, history of Grade 3 hypersensitivity to oxaliplatin, history of allergic reaction to folic acid
Female subject is pregnant or lactating
Known history of genetic or acquired immune suppression disease including Human Immunodeficiency Virus (HIV); subjects on immune suppressive therapy for organ transplant
Inability to swallow pills, malabsorption syndrome or gastrointestinal disease, major resection of the stomach or small bowel, or gastric bypass
Uncontrolled neuro-psychiatric disorder or altered mental status
Peripheral neuropathy ≥ Grade 2
Participating in another interventional protocol

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01478594

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Locations

United States, Arizona
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States, 85234
Genesis Cancer Center
Hot Springs, Arizona, United States, 71913
Arizona Clinical Research Center
Tucson, Arizona, United States, 85715
United States, California
University of California San Diego
La Jolla,, California, United States, 92093
UC Irvine Medical Center, Division of Hematology/Oncology
Orange, California, United States, 92868
Desert Hematology Oncology Medical Group, Inc.
Rancho Mirage, California, United States, 92270
United States, Colorado
Mountain Blue Cancer Care Center
Wheat Ridge, Colorado, United States, 80033
United States, Connecticut
Stamford Hospital
Stamford, Connecticut, United States, 06902
United States, Florida
University of Florida, Davis Cancer Center (VA)
Gainesville, Florida, United States, 32610
Cleveland Clinic Florida
Weston, Florida, United States, 33331
United States, Hawaii
Kaiser Foundation Hospitals
Honolulu, Hawaii, United States, 96819
University of Hawaii
Honolulu, Hawaii, United States, 96813
Queen's Medical Center
Honolulu, Hawaii, United States, 96813
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Illinios Cancer Care
Peoria, Illinois, United States, 61615
United States, Indiana
Investigative Clinical Research of Indiana, LLC
Indianapolis, Indiana, United States, 46260
Horizon Oncology Research, Inc.
Lafayette, Indiana, United States, 47905
United States, Maryland
Associates of Oncology Hematology, P.C.
Rockville, Maryland, United States, 20850
United States, Michigan
University of Michigan Hospital and Health Center
Ann Arbor, Michigan, United States, 48109
United States, New York
NYU Cancer Institute
New York, New York, United States, 10016
United States, North Carolina
Alamance Regional Medical Center Cancer Center
Burlington, North Carolina, United States, 27215
United States, Ohio
Tri Country Hematology / Oncology
Canton, Ohio, United States, 44718
Signal Point Clinical Research Center, LLC
Middletown, Ohio, United States, 45042
United States, Oklahoma
Cancer Care Associates
Tulsa, Oklahoma, United States, 74136
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
St. Luke's Hospital and Health Network
Bethlehem, Pennsylvania, United States, 18015
United States, Utah
Northern Utah Associates
Ogden, Utah, United States, 84403
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Australia, New South Wales
St George Hospital
Kogarah, New South Wales, Australia, 2217
Tweed Hospital
Tweed Heads, New South Wales, Australia, 2485
Calvary Mater Newcastle
Waratah, New South Wales, Australia, 2298
Australia, South Australia
Flinders Medical Centre
Bedford Park, South Australia, Australia, 5042
Australia, Tasmania
Royal Hobart Hospital
Hobart, Tasmania, Australia, 7000
Australia, Victoria
Ballarat Health Services
Ballarat, Victoria, Australia, 3350
Cabrini Hospital Malvern
Malvern, Victoria, Australia, 3144
Border Medical Oncology
Wodonga, Victoria, Australia, 3690
Austria
Medizinische Universitat Graz
Graz, Austria, 8036
Salzburger Landesklinken
Salzburg, Austria, 5020
Klinikum Wels-Grieskirchen GmbH
Wels, Austria, 4600
Belgium
Ziekenhuisnetwerk Antwerpen - AZ Middelheim
Antwerpen, Belgium, 2020
Imelda VZW
Bonheiden, Belgium, 2820
AZ Sint-Lucas Brugge
Brugge, Belgium, 8310
AZ Groeninge - Campus Sint-Niklaas
Kortrijk, Belgium, 8500
Canada, British Columbia
British Columbia Cancer Agency
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Nova Scotia
QEII Health Services Centre
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Quebec
Hopital De La Cite-De-La-Sante
Laval, Quebec, Canada, H7M 3L9
Hopital Saint-Luc - Pavillon Principal
Montreal, Quebec, Canada, H2X 3J4
Canada
Chuq Centre Hospitalier Universitaire De Quebec
Quebec, Canada, G1R 2J6
Czech Republic
Masarykuv onkologicky ustav
Brno, Czech Republic, 656 53
Fakultni nemocnice Hradec Kralove
Hradec Kralove, Czech Republic, 500 05
Finland
Tampereen yliopistollinen sairaala
Tampere, Finland, FI-33520
Turun yliopistollinen keskussairaala
Turku, Finland, FI-20520
Hungary
Orszagos Onkologiai Intezet
Budapest, Hungary, 1122
Petz Aladar Megyei Oktato Korhaz
Gyor, Hungary, 9024
Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza
Gyula, Hungary, 5700
Fejer Megyei Szent Gyorgy Korhaz
Szekesfehervar, Hungary, 8000
Italy
Azienda Ospedaliero- Universitaria di Bologna - Policlinico S.Orsola-Malpighi
Bologna, Italy, 40128
Fondazione del Piemonte per I'Oncologia IRCC
Candiolo, Italy, 10060
IRCCS Azienda Ospedaliera Universitaria San Martino - Istituto Nazionale per la Ricerca sul Cancro
Genova, Italy, 16132
Istituto Clinico Humanitas
Rozzano (MI), Italy, 20089
Netherlands
Amphia Ziekenhuis
Breda, Netherlands, 4819 EV
Spain
Hospital Universitario Miguel Servet
Zaragoza, Aragon, Spain, 50009
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, Spain, 39008
Corporacio Sanitaria Parc Tauli
Sabadell, Cataluna, Spain, 08208
Hospital Mutua de Terrassa
Terrassa, Cataluna, Spain, 08221
Centro Oncologico de Galicia
La Coruna, Galicia, Spain, 15009
Centro Integral Oncologico Clara Campal
Madrid, Spain, 28050
United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom, CB2 2QQ
Western General Hospital
Edinburgh, United Kingdom, EH4 2XU
Beatson West of Scotland Cancer Center
Glasgow, United Kingdom, G12 0YN
University College Hospital
London, United Kingdom, NW1 2BU
Maidstone Hospital
Maidstone, United Kingdom, ME16 9QQ
Christie Hospital
Manchester, United Kingdom, M20 4BX
Peterborough and Stamford Hospitals NHS Foundation Trust
Peterborough, United Kingdom, PE3 6DA

Sponsors and Collaborators

Astellas Pharma Inc

AVEO Pharmaceuticals, Inc.

Investigators

Study Director:

Medical Director

Astellas Pharma Global Development

More Information

No publications provided

Responsible Party:	Astellas Pharma Inc
ClinicalTrials.gov Identifier:	NCT01478594 History of Changes
Other Study ID Numbers:	4130-CL-0201, 2011-003502-24
Study First Received:	November 21, 2011
Last Updated:	May 9, 2013
Health Authority:	United States: Food and Drug Administration Canada: Health Canada Belgium: Federal Agency for Medicinal Products and Health Products United Kingdom: Medicines and Healthcare Products Regulatory Agency Czech Republic: State Institute for Drug Control Australia: Department of Health and Ageing Therapeutic Goods Administration Italy: The Italian Medicines Agency Spain: Ministry of Health and Consumption Austria: Agency for Health and Food Safety Finland: Finnish Medicines Agency Hungary: National Institute of Pharmacy Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Astellas Pharma Inc:

metastatic colorectal cancer
Avastin
bevacizumab
tivozanib

mFOLFOX6
BATON-CRC
AV951
ASP4130

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
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 17, 2013