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Trial registered on ANZCTR


Registration number
ACTRN12607000589482
Ethics application status
Approved
Date submitted
12/11/2007
Date registered
16/11/2007
Date last updated
14/12/2010
Type of registration
Prospectively registered

Titles & IDs
Public title
Brivanib and Cetuximab versus Cetuximab and Placebo in treating patients with metastatic colorectal cancer who have been previously treated with combination chemotherapy
Scientific title
Phase III randomised study of Brivanib Alaninate (BMS-582664) in combination with Cetuximab (Erbitux 'Registered trade mark') versus placebo in combination with Cetuximab (Erbitux 'Registered trade mark') in patients with K-Ras wild type tumours previously treated with combination chemotherapy for metastatic colorectal carcinoma to compare overall survival.
Secondary ID [1] 491 0
NCICCTG-CO.20 (National Cancer Institute of Canada Clinical Trials Group)
Secondary ID [2] 492 0
BMS-CA182009 (Bristol Myers-Squibb, Canada)
Secondary ID [3] 493 0
AGITG-NCICCTG-CO.20 (Australian Gastrointestinal Trials Group)
Universal Trial Number (UTN)
Trial acronym
CO.20
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Colorectal Cancer 2534 0
Condition category
Condition code
Cancer 2635 2635 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This ia a randomised, double-blind, multicentre study. Patients will be stratified by centre and ECOG (Eastern Cooperative Oncology Group) perfomance status (ie: 0 or 1 versus 2) into one of two treatment arms.
Arm I: Patients will receive Brivanib 800mg orally daily, in addition to an initial loading dose infusion of Cetuximab (Erbitux) 400mg/m2 over 120 minutes. Thereafter, patients will receive weekly maintenance infusions of Cetuximab 250mg/m2 over 60 minutes.
Arm II: Patients will receive placebo orally daily, and an initial loading dose of Cetuximab 400mg/m2 IV over 120 minutes. Thereafter, the patients will receive a weekly maintenance infusion of Cetuximab 250mg/m2 IV over 60 minutes.
Intervention code [1] 2266 0
Treatment: Drugs
Comparator / control treatment
Treatment Arm II is the comparator (control) group. These patients will receive the placebo, in addition to a loading dose of Cetuximab 400mg/m2 intravenously, followed by weekly maintenance infusions of Cetuximab 250mg/m2.
Control group
Placebo

Outcomes
Primary outcome [1] 3544 0
To compare the overall survival of patients with previously treated metastatic colorectal cancer treated with Brivanib in combination with Cetuximab with those treated with placebo and Cetuximab
Timepoint [1] 3544 0
At interim analysis point (ie: > 263 deaths) and end of study
Secondary outcome [1] 5933 0
Compare progression-free survival in both treatment groups
Compare objective response rate and duration of response in both treatment groups.
Compare quality of life in both treatment groups.
Compare health utilities in both treatment groups.
Conduct a comparative economic evaluation of both treatment groups.
Evaluate safety profile of Cetuximab and Brivanib and Cetuximab alone in this patient population.
Timepoint [1] 5933 0
At end of study

Eligibility
Key inclusion criteria
Age > 18 years Histologically confirmed metastatic colorectal cancer Confirmed K-Ras wild type tumour Previously treated with thymidylate synthase inhibitor Previously failed treatment with irinotecan-containing regimen and oxaliplatin-containing regimen where failure is defined as either progression of disease or intolerance to the regimen due to severe allergic reaction or delayed recovery from toxicity. Measurable or evaluable disease Minimum 4 weeks have elapsed since recent surgery, chemotherapy, treatment with another investigational agent, or radiation therapy ECOG performace status of 0, 1, or 2 Provision of blood/tumor speciments for correlative studies
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
K-Ras mutant, indeterminate, or no tumour tissue available for testing History of other malignancies other than non-melanoma skin cancer, in-situ cancer of the cervix, or other curatively treated solid tumors with no evidence of disease for > 5 years Any active disease condition which would render protocol treatment dangerous or does not permit compliance with protocol Uncontrolled or significant cardiovascular disease, hypertension, or a history of thromboembolic event in last 6 months Central nervous system metastases Prior treatment with Cetuximab or other EGFR (epidermal growth factor receptor) pathway targetting agent or murine monoclonal antibody

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)
Subjects will be enrolled and randomised to the study via a web-based registration & randomisation system (ie: MANGO), housed at Queen's University, Kingston, Ontario, Canada.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Dynamic Minimisation procedure
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
26/03/2008
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
750
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,QLD,SA,WA,NT,TAS
Recruitment postcode(s) [1] 486 0
3000 - 3999
Recruitment postcode(s) [2] 487 0
4000 - 4999
Recruitment postcode(s) [3] 488 0
5000 - 5999
Recruitment postcode(s) [4] 489 0
6000 - 6999
Recruitment postcode(s) [5] 490 0
7000 - 7999
Recruitment postcode(s) [6] 491 0
2000 - 2999
Recruitment outside Australia
Country [1] 649 0
New Zealand
State/province [1] 649 0
Country [2] 650 0
Singapore
State/province [2] 650 0
Country [3] 651 0
Canada
State/province [3] 651 0

Funding & Sponsors
Funding source category [1] 2780 0
Other Collaborative groups
Name [1] 2780 0
Australasian Gastro-Intestinal Trials Group (AGITG)
Country [1] 2780 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Gastro-Intestinal Trials Group (AGITG)
Address
University of Sydney
Locked Bag 77
Camperdown NSW, 1450
Country
Australia
Secondary sponsor category [1] 2512 0
Government body
Name [1] 2512 0
National Cancer Institute of Canada
Address [1] 2512 0
10 Alcorn Avenue, Suite 200
Toronto, Ontario, M4V 3B1
Country [1] 2512 0
Canada

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4700 0
Cancer Institute NSW
Ethics committee address [1] 4700 0
Level 1, Biomedical Building
Australian Technology Park
1 Central Avenue, EVELEIGH, NSW, 2015
Ethics committee country [1] 4700 0
Australia
Date submitted for ethics approval [1] 4700 0
27/08/2007
Approval date [1] 4700 0
05/03/2008
Ethics approval number [1] 4700 0
2007C/09/016

Summary
Brief summary
This study is assessing two different chemotherapy treatments – Brivanib and Cetuximab versus Cetuximab and standard treatment – in treating people with metastatic (secondary distant) colorectal (K-Ras Wild Type) cancer who have previously been treated with combination chemotherapy.

Who is it for?

You can join this study if you have completed the standard chemotherapy for metastatic colorectal cancer.

Trial details

Participants will be randomly divided into two groups. One group will receive a combination of a compound known as oral Brivanib in combination with Cetuximab; the other will receive standard treatment in combination with Cetuximab. The trial will eventually assess if there is a difference in overall survival between the two groups.

Brivanib blocks a compound known as ‘vascular endothelial growth factor receptor 2’ (VEGFR2) and this may result in the inhibition of tumour blood vessel growth. Cetuximab blocks another factor called the ‘epidermal growth factor receptor’ (EGFR) and so inhibits cell growth. If your cancer has increased in size on standard treatment for metastatic colorectal cancer (which might included 5-fluorouracil, oxaliplatin and irinotecan), your treatment options are limited. Cetuximab works in this setting but it is not part of the standard treatment. This purpose of this trial is to test if the combination of Brivanib and Cetuximab versus Cetuximab alone improve survival if the treatment you have been receiving has not worked.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28169 0
Address 28169 0
Country 28169 0
Phone 28169 0
Fax 28169 0
Email 28169 0
Contact person for public queries
Name 11326 0
Dr. Jeremy Shapiro
Address 11326 0
Dept of Medical Oncology
Cabrini Hospital
Suite 19, 183 Wattletree Road
MALVERN, VIC, 3144
Country 11326 0
Australia
Phone 11326 0
+613 9509 1866
Fax 11326 0
+613 9509 6014
Email 11326 0
[email protected]
Contact person for scientific queries
Name 2254 0
Dr. Jeremy Shapiro
Address 2254 0
Dept of Medical Oncology
Cabrini Hospital
Suite 19, 183 Wattletree Road
MALVERN, VIC, 3144
Country 2254 0
Australia
Phone 2254 0
+613 9509 1866
Fax 2254 0
+613 9509 6014
Email 2254 0
[email protected]

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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.