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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
1/12/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2015
Sample size
Target
Accrual to date
Final
265
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.

Results are available at https://clinicaltrials.gov/study/NCT01478594