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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01478594




Registration number
NCT01478594
Ethics application status
Date submitted
21/11/2011
Date registered
23/11/2011
Date last updated
8/07/2015

Titles & IDs
Public title
A Study Combining mFOLFOX6 With Tivozanib or Bevacizumab in Patients With Metastatic Colorectal Cancer as First Line Therapy
Scientific 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
Secondary ID [1] 0 0
2011-003502-24
Secondary ID [2] 0 0
4130-CL-0201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tivozanib
Treatment: Drugs - Bevacizumab
Treatment: Drugs - mFOLFOX6

Experimental: Tivozanib + mFOLFOX6 - Participants 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.

Active comparator: Bevacizumab + mFOLFOX6 - Participants 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.


Treatment: Drugs: Tivozanib
Capsules for oral administration

Treatment: Drugs: Bevacizumab
Solution for intravenous infusion

Treatment: Drugs: mFOLFOX6
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Investigator-assessed Progression-Free Survival (PFS)
Timepoint [1] 0 0
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 outcome [1] 0 0
Progression-Free Survival (PFS) Based on Independent Radiological Review (IRR)
Timepoint [1] 0 0
3 years
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
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 outcome [3] 0 0
Objective Response Rate (ORR)
Timepoint [3] 0 0
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 outcome [4] 0 0
Duration of Response (DoR)
Timepoint [4] 0 0
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 outcome [5] 0 0
Time to Treatment Failure (TTF)
Timepoint [5] 0 0
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 outcome [6] 0 0
Health Related Quality of Life (HRQoL)
Timepoint [6] 0 0
3 years
Secondary outcome [7] 0 0
Safety as Assessed by Physical Examination, Vital Signs, Laboratory Assessments, 12-lead Electrocardiogram (ECGs), and Adverse Events (AEs)
Timepoint [7] 0 0
From first dose through 30 days after last dose of either tivozanib or bevacizumab, until the data cut-off date of 28 February 2014. The median duration of treatment was 168.0 days in the tivozanib (tiv) arm and 162.0 days in the bevacizumab (bev) arm.
Secondary outcome [8] 0 0
Progression-free Survival Events by Lactate Dehydrogenase (LDH) Level
Timepoint [8] 0 0
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 outcome [9] 0 0
Progression-free Survival Events by Serum Vascular Endothelial Growth Factor-A (VEGF-A) Level
Timepoint [9] 0 0
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 outcome [10] 0 0
Progression-free Survival Events by Serum Vascular Endothelial Growth Factor-C (VEGF-C) Level
Timepoint [10] 0 0
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 outcome [11] 0 0
Progression-free Survival Events by Serum VEGF-C / VEGF-A Ratio
Timepoint [11] 0 0
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 outcome [12] 0 0
Progression-Free Survival Events by Soluble Vascular Endothelial Growth Factor Receptor-2 (sVEGFR-2) Level
Timepoint [12] 0 0
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 outcome [13] 0 0
Progression-Free Survival Events by Soluble Vascular Endothelial Growth Factor Receptor-3 (sVEGFR-3) Level
Timepoint [13] 0 0
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 outcome [14] 0 0
Progression-Free Survival Events by Serum Interleukin-8 (IL-8) Level
Timepoint [14] 0 0
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 outcome [15] 0 0
Progression-Free Survival Events by Serum Neuropilin Level
Timepoint [15] 0 0
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 outcome [16] 0 0
Progression-Free Survival Events by Tumor VEGF-A Ribonucleic Acid (RNA) Level
Timepoint [16] 0 0
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 outcome [17] 0 0
Progression-Free Survival Events by Tumor VEGF-C RNA Level
Timepoint [17] 0 0
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 outcome [18] 0 0
Progression-Free Survival Events by Tumor VEGF-C / VEGF-A RNA Ratio
Timepoint [18] 0 0
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 outcome [19] 0 0
Progression-Free Survival Events by Tumor VEGF-D RNA Level
Timepoint [19] 0 0
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 outcome [20] 0 0
Progression-Free Survival Events by Tumor Placental Growth Factor (PIGF) RNA Level
Timepoint [20] 0 0
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.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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,
* 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
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,TAS,VIC
Recruitment hospital [1] 0 0
St George Hospital - Kogarah
Recruitment hospital [2] 0 0
Tweed Hospital - Tweed Heads
Recruitment hospital [3] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [4] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [5] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [6] 0 0
Ballarat Health Services - Ballarat
Recruitment hospital [7] 0 0
Cabrini Hospital Malvern - Malvern
Recruitment hospital [8] 0 0
Border Medical Oncology - Wodonga
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment postcode(s) [4] 0 0
5042 - Bedford Park
Recruitment postcode(s) [5] 0 0
7000 - Hobart
Recruitment postcode(s) [6] 0 0
3350 - Ballarat
Recruitment postcode(s) [7] 0 0
3144 - Malvern
Recruitment postcode(s) [8] 0 0
3690 - Wodonga
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Hawaii
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Oklahoma
Country [14] 0 0
United States of America
State/province [14] 0 0
Oregon
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
Utah
Country [17] 0 0
United States of America
State/province [17] 0 0
Washington
Country [18] 0 0
Austria
State/province [18] 0 0
Graz
Country [19] 0 0
Austria
State/province [19] 0 0
Salzburg
Country [20] 0 0
Austria
State/province [20] 0 0
Wels
Country [21] 0 0
Belgium
State/province [21] 0 0
Antwerpen
Country [22] 0 0
Belgium
State/province [22] 0 0
Bonheiden
Country [23] 0 0
Belgium
State/province [23] 0 0
Brugge
Country [24] 0 0
Belgium
State/province [24] 0 0
Kortrijk
Country [25] 0 0
Canada
State/province [25] 0 0
British Columbia
Country [26] 0 0
Canada
State/province [26] 0 0
Nova Scotia
Country [27] 0 0
Canada
State/province [27] 0 0
Quebec
Country [28] 0 0
Czech Republic
State/province [28] 0 0
Brno
Country [29] 0 0
Czech Republic
State/province [29] 0 0
Hradec Kralove
Country [30] 0 0
Finland
State/province [30] 0 0
Tampere
Country [31] 0 0
Finland
State/province [31] 0 0
Turku
Country [32] 0 0
Hungary
State/province [32] 0 0
Budapest
Country [33] 0 0
Hungary
State/province [33] 0 0
Gyor
Country [34] 0 0
Hungary
State/province [34] 0 0
Gyula
Country [35] 0 0
Hungary
State/province [35] 0 0
Szekesfehervar
Country [36] 0 0
Italy
State/province [36] 0 0
Bologna
Country [37] 0 0
Italy
State/province [37] 0 0
Candiolo
Country [38] 0 0
Italy
State/province [38] 0 0
Genova
Country [39] 0 0
Italy
State/province [39] 0 0
Rozzano (MI)
Country [40] 0 0
Netherlands
State/province [40] 0 0
Breda
Country [41] 0 0
Spain
State/province [41] 0 0
Aragon
Country [42] 0 0
Spain
State/province [42] 0 0
Cantabria
Country [43] 0 0
Spain
State/province [43] 0 0
Cataluna
Country [44] 0 0
Spain
State/province [44] 0 0
Galicia
Country [45] 0 0
Spain
State/province [45] 0 0
Madrid
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Cambridge
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Edinburgh
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Glasgow
Country [49] 0 0
United Kingdom
State/province [49] 0 0
London
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Maidstone
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Manchester
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Peterborough

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AVEO Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
AVEO Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.