Trial record 1 of 1 for:    4130-CL-0201
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A Study Combining mFOLFOX6 With Tivozanib or Bevacizumab in Patients With Metastatic Colorectal Cancer as First Line Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01478594
First received: November 21, 2011
Last updated: May 15, 2015
Last verified: May 2015
Results First Received: February 19, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Colorectal Cancer
Interventions: Drug: Tivozanib
Drug: Bevacizumab
Drug: mFOLFOX6

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were at least 18 years of age with Stage IV metastatic colorectal cancer (mCRC) and measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Version 1.1).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomized in a 2:1 ratio (tivozanib to bevacizumab) and stratified by lactate dehydrogenase (LDH) status (< 1.5 x the upper limit of normal [ULN] or > 1.5 x ULN), origin of cancer (rectal or colon) and number of metastatic sites (1 or > 2).

Reporting Groups
  Description
Tivozanib + mFOLFOX6 Participants received 1.5 mg tivozanib orally once daily beginning on Day 1 of each 28-day cycle for 21 days followed by 7 days off treatment. Participants also received modified FOLFOX6 (mFOLFOX6) chemotherapy consisting of oxaliplatin, 85 mg/m^2, leucovorin 400 mg/m^2, and 5-fluorouracil 400 mg/m^2 bolus then 2400 mg/m^2 every 2 weeks on Days 1 and 15 of each cycle.
Bevacizumab + mFOLFOX6 Participants received 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.

Participant Flow:   Overall Study
    Tivozanib + mFOLFOX6     Bevacizumab + mFOLFOX6  
STARTED     177     88  
Treated     177     87  
COMPLETED     112 [1]   60 [1]
NOT COMPLETED     65     28  
Randomized but Never Received Study Drug                 0                 1  
Death                 45                 18  
Lost to Follow-up                 3                 1  
Withdrawal by Subject                 9                 3  
Study Closed by Sponsor                 8                 5  
[1] Participants still on study as of 28 February 2014



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Tivozanib + mFOLFOX6 Participants received 1.5 mg tivozanib orally once daily beginning on Day 1 of each cycle for 21 days followed by 7 days off treatment. Participants also received mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle.
Bevacizumab + mFOLFOX6 Participants received 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.
Total Total of all reporting groups

Baseline Measures
    Tivozanib + mFOLFOX6     Bevacizumab + mFOLFOX6     Total  
Number of Participants  
[units: participants]
  177     88     265  
Age  
[units: years]
Mean (Standard Deviation)
  61.9  (9.58)     62.6  (11.17)     62.2  (10.12)  
Gender  
[units: participants]
     
Female     59     33     92  
Male     118     55     173  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     6     2     8  
Not Hispanic or Latino     170     86     256  
Unknown or Not Reported     1     0     1  
Race/Ethnicity, Customized  
[units: participants]
     
White     169     85     254  
Black or African American     2     0     2  
Asian     3     2     5  
Native Hawaiian or other Pacific Islander     1     1     2  
Other     2     0     2  
Region of Enrollment  
[units: participants]
     
United States     44     26     70  
Hungary     24     8     32  
Czech Republic     12     9     21  
Canada     13     4     17  
Finland     5     1     6  
Spain     22     8     30  
Belgium     10     9     19  
Austria     8     3     11  
Australia     15     9     24  
Netherlands     1     1     2  
United Kingdom     19     7     26  
Italy     4     3     7  
Eastern Cooperative Oncology Group (ECOG) performance status [1]
[units: participants]
     
ECOG Performance Status 0     95     58     153  
ECOG Performance Status 1     82     30     112  
ECOG Performance Status 2     0     0     0  
ECOG Performance Status 3     0     0     0  
ECOG Performance Status 4     0     0     0  
Lactate dehydrogenase (LDH) Status [2]
[units: participants]
     
< 1.5 Upper Limit of Normal     127     64     191  
≥ 1.5 Upper Limit of Normal     50     24     74  
Origin of Cancer  
[units: participants]
     
Rectal     53     24     77  
Colon     124     64     188  
Number of metastatic sites/organs  
[units: participants]
     
1     56     30     86  
2     80     34     114  
3     29     21     50  
≥ 4     12     3     15  
Kirsten rat sarcoma (KRAS) Mutation Status  
[units: participants]
     
Wild-type     33     21     54  
Mutant     23     16     39  
Unknown     121     51     172  
Time Since Initial Diagnosis  
[units: months]
Mean (Standard Deviation)
  9.41  (20.473)     10.88  (21.055)     9.90  (20.640)  
Number of metastatic sites at screening  
[units: metastatic┬ásites]
Mean (Standard Deviation)
  2.0  (1.02)     2.0  (0.85)     2.0  (0.97)  
[1] ECOG criteria: 0: Fully active. 1: Ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of all self-care. 3: Capable of limited self-care, confined to bed or chair more than 50% of waking hours. 4: Completely disabled, no self-care, totally confined to bed or chair. 5: Dead.
[2] The upper limit of normal (ULN) from the site was used.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Investigator-assessed Progression-Free Survival (PFS)   [ Time Frame: 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. ]

2.  Secondary:   Progression-Free Survival (PFS) Based on Independent Radiological Review (IRR)   [ Time Frame: 3 years ]

3.  Secondary:   Overall Survival (OS)   [ Time Frame: 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. ]

4.  Secondary:   Objective Response Rate (ORR)   [ Time Frame: 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. ]

5.  Secondary:   Duration of Response (DoR)   [ Time Frame: 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. ]

6.  Secondary:   Time to Treatment Failure (TTF)   [ Time Frame: 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. ]

7.  Secondary:   Health Related Quality of Life (HRQoL)   [ Time Frame: 3 years ]

8.  Secondary:   Safety as Assessed by Physical Examination, Vital Signs, Laboratory Assessments, 12-lead Electrocardiogram (ECGs), and Adverse Events (AEs)   [ Time Frame: 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. ]

9.  Secondary:   Progression-free Survival Events by Lactate Dehydrogenase (LDH) Level   [ Time Frame: 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. ]

10.  Secondary:   Progression-free Survival Events by Serum Vascular Endothelial Growth Factor-A (VEGF-A) Level   [ Time Frame: 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. ]

11.  Secondary:   Progression-free Survival Events by Serum Vascular Endothelial Growth Factor-C (VEGF-C) Level   [ Time Frame: 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. ]

12.  Secondary:   Progression-free Survival Events by Serum VEGF-C / VEGF-A Ratio   [ Time Frame: 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. ]

13.  Secondary:   Progression-Free Survival Events by Soluble Vascular Endothelial Growth Factor Receptor-2 (sVEGFR-2) Level   [ Time Frame: 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. ]

14.  Secondary:   Progression-Free Survival Events by Soluble Vascular Endothelial Growth Factor Receptor-3 (sVEGFR-3) Level   [ Time Frame: 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.  Secondary:   Progression-Free Survival Events by Serum Interleukin-8 (IL-8) Level   [ Time Frame: 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. ]

16.  Secondary:   Progression-Free Survival Events by Serum Neuropilin Level   [ Time Frame: 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. ]

17.  Secondary:   Progression-Free Survival Events by Tumor VEGF-A Ribonucleic Acid (RNA) Level   [ Time Frame: 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. ]

18.  Secondary:   Progression-Free Survival Events by Tumor VEGF-C RNA Level   [ Time Frame: 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. ]

19.  Secondary:   Progression-Free Survival Events by Tumor VEGF-C / VEGF-A RNA Ratio   [ Time Frame: 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. ]

20.  Secondary:   Progression-Free Survival Events by Tumor VEGF-D RNA Level   [ Time Frame: 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. ]

21.  Secondary:   Progression-Free Survival Events by Tumor Placental Growth Factor (PIGF) RNA Level   [ Time Frame: 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. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Executive Medical Director, Global Medical Oncology
Organization: Astellas Pharma Global Development, Inc.
e-mail: Astellas.resultsdisclosure@astellas.com


No publications provided


Responsible Party: AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01478594     History of Changes
Other Study ID Numbers: 4130-CL-0201, 2011-003502-24
Study First Received: November 21, 2011
Results First Received: February 19, 2015
Last Updated: May 15, 2015
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)