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AzTrials

Colorectal CancerPhase 3NCT00640471

Cetuximab With or Without Brivanib in Treating Patients With K-Ras Wild Type Tumours and Metastatic Colorectal Cancer

A Phase 3 study testing cetuximab and brivanib alaninate in people with Colorectal Cancer, run by NCIC Clinical Trials Group at 37 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

RATIONALE: Brivanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
cetuximab and brivanib alaninate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
750 participants
Where
37 sitesCanada
Study dates
12 May 2008to 10 Jan 2013
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ECOG performance status 0-2
  • Absolute granulocyte count ≥ 1.5 x 10^9/L
  • Platelet count ≥ 75 x 10^9/L
  • Hemoglobin ≥ 80 g/L
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (2.0 times ULN with documented liver metastases)
  • ALT and AST ≤ 2.5 times ULN (5.0 times ULN with documented liver metastases)
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  • Serum creatinine ≤ 1.5 times ULN or creatinine clearance > 50 mL/min
  • Magnesium > 0.5 mmol/L (1.2 mg/dL)
  • LVEF > 45% by ECHO or MUGA scan
  • No proteinuria ≥ 2+ on dipstick or ≥ 1 g on 24 hour urine collection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to, during, and for 12 weeks after completion of study treatment
  • Able (i.e., sufficiently fluent) and willing to complete the quality of life (EORTC QLQ-C30 and Skindex-16) and health utilities questionnaires (HUI3) in either English or French

Who cannot join

  • A history of other malignancies, except: adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
  • Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy
  • Any condition (e.g., psychological, geographical, etc.) that does not permit compliance with the protocol
  • Uncontrolled or significant cardiovascular disease including any of the following:
  • Myocardial infarction within 12 months
  • Uncontrolled angina within 6 months
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  • Clinically significant congestive heart failure
  • Stroke, transient ischemic attack, or other ischemic event within 12 months
  • Severe cardiac valve dysfunction
  • Uncontrolled hypertension (consistent elevation of systolic BP > 150 and diastolic BP > 100 mmHg)
  • History of a thromboembolic event in the last 6 months despite being treated with anticoagulation
  • Patients are eligible if they have experienced a thromboembolic event greater than 6 months previously and have initiated and are stable on anticoagulation or if they have previously initiated and are stable on anticoagulation for prevention of thromboembolic events
  • Severe restrictive lung disease or radiological pulmonary findings of "interstitial lung disease" on the baseline chest x-ray which, in the opinion of the investigator, represents significant pathology
  • Serious non-healing wounds, ulcers, or bone fractures
  • History of allergy to brivanib (alaninate or related drug class
  • Unable to swallow tablets
  • PRIOR CONCURRENT THERAPY:
  • See Disease Characteristics
  • Adequately recovered from recent surgery, chemotherapy and/or radiation therapy
  • At least 4 weeks must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or prior radiation therapy
  • No prior cetuximab or other therapy* with targets the EGFR pathway (e.g., erlotinib hydrochloride, gefitinib hydrochloride, panitumumab)
  • May have received a single prior regimen which targets the VEGFR pathway (e.g., bevacizumab , vatalanib, AZD2171, sorafenib tosylate, sunitinib malate, or others)
  • No prior murine monoclonal antibody therapy (e.g., edrecolomab)
  • No other concurrent chemotherapy
  • No other concurrent therapies targeting the EGFR pathway (e.g., erlotinib, gefitinib, panitumumab, or others) or other therapies targeting the VEGFR pathway (e.g., bevacizumab , vatalanib, AZD2171, sorafenib tosylate, sunitinib malate, or others)
  • Concurrent antihypertensive therapies allowed
  • Concurrent aspirin allowed
  • No other concurrent noncytotoxic experimental agents

Trial locations and contacts

37 sites in 1 country.

37 sites in 1 country

Canada37 sites

  • BCCA - Abbotsford Centre

    Abbotsford British Columbia, British Columbia, V2S 0C2

  • The Royal Victoria Hospital

    Barrie, Ontario, L4M 6M2

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • PEI Cancer Treatment Centre,Queen Elizabeth Hospital

    Charlottetown, Prince Edward Island, C1A 8T5

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Hopital Charles LeMoyne

    Greenfield Park, Quebec, J4V 2H1

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • BCCA - Cancer Centre for the Southern Interior

    Kelowna, British Columbia, V1Y 5L3

  • Cancer Centre of Southeastern Ontario at Kingston

    Kingston, Ontario, K7L 5P9

  • Grand River Regional Cancer Centre

    Kitchener, Ontario, N2G 1G3

  • L'Hotel-Dieu de Levis

    Lévis, Quebec, G6V 3Z1

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • The Moncton Hospital

    Moncton, New Brunswick, E1C 6Z8

  • The Vitalite Health Network - Dr. Leon Richard

    Moncton, New Brunswick, E1C 8X3

  • CHUM - Hopital Notre-Dame

    Montreal, Quebec, H2L 4M1

  • McGill University - Dept. Oncology

    Montreal, Quebec, H2W 1S6

  • Hopital du Sacre-Coeur de Montreal

    Montreal, Quebec, H4J 1C5

  • Stronach Regional Health Centre at Southlake

    Newmarket, Ontario, L3Y 2P9

  • Lakeridge Health Oshawa

    Oshawa, Ontario, L1G 2B9

  • Ottawa Health Research Institute - General Division

    Ottawa, Ontario, K1H 8L6

  • CHUQ-Pavillon Hotel-Dieu de Quebec

    Québec, Quebec, G1R 2J6

  • CHA-Hopital Du St-Sacrement

    Québec, Quebec, G1S 4L8

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • Atlantic Health Sciences Corporation

    Saint John, New Brunswick, E2L 4L2

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • Algoma District Cancer Program

    Sault Ste. Marie, Ontario, P6B 0A8

  • Centre hospitalier universitaire de Sherbrooke

    Sherbrooke, Quebec, J1H 5N4

  • Niagara Health System

    St. Catharines, Ontario, L2R 7C6

  • Dr. H. Bliss Murphy Cancer Centre

    St. John's, Newfoundland and Labrador, AIB 3V6

  • BCCA - Fraser Valley Cancer Centre

    Surrey, British Columbia, V3V 1Z2

  • Thunder Bay Regional Health Science Centre

    Thunder Bay, Ontario, P7B 6V4

  • Toronto East General Hospital

    Toronto, Ontario, M4C 3E7

  • Odette Cancer Centre

    Toronto, Ontario, M4N 3M5

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

  • Univ. Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

  • BCCA - Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

About this study

Official title: A Phase III Randomized Study of Brivanib Alaninate (BMS-582664) in Combination With Cetuximab (Erbitux®) Versus Placebo in Combination With Cetuximab (Erbitux®) in Patients With K-RAS Wild Type Tumors Previously Treated With Combination Chemotherapy for Metastatic Colorectal Carcinoma

RATIONALE: Brivanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving brivanib together with cetuximab is more effective than cetuximab alone in treating patients with metastatic colorectal cancer.

PURPOSE: This randomized phase III trial is studying cetuximab to see how well it works compared with cetuximab given together with brivanib in treating patients with metastatic colorectal cancer.

Read the detailed description

OBJECTIVES:

Primary

  • To compare the overall survival of patients with previously treated K-Ras wild type metastatic colorectal carcinoma treated with brivanib alaninate in combination with cetuximab versus placebo in combination with cetuximab.

Secondary

  • To compare the progression-free survival of these patients.
  • To compare the objective response rate and duration of response in these patients.
  • To compare the quality of life of these patients.
  • To compare the health utilities of these patients.
  • To conduct a comparative economic evaluation of these patients.
  • To evaluate the safety profile of this regimen in these patients.
  • To explore an association between FGF-2, BRAF mutations, amphiregulin (AREG) and epiregulin (EREG) as determined from paraffin embedded tumor specimens and the potential for clinical benefit from the addition of brivanib alaninate or placebo to cetuximab in terms of overall survival, progression-free survival and objective response rate compared to cetuximab alone.
  • To explore associations with mRNA and/or protein expression and/or variations in genes associated with epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), angiogenesis, and other related pathways and the potential for clinical benefit from the addition of brivanib alaninate to cetuximab in terms of overall survival, progression-free survival, and objective response rate compared to cetuximab alone.
  • To explore an association with changes of Collagen IV in the blood and the potential for clinical benefit from the addition of brivanib alaninate to cetuximab in terms of overall survival, progression-free survival and objective response rate compared to cetuximab alone.
  • To establish a comprehensive tumor bank linked to a clinical database for the further study of molecular markers in colorectal cancer.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center and ECOG performance status (0-1 vs 2). Patients are randomized to 1 of 2 arms.

  • Arm I: Patients receive oral brivanib alaninate once daily and cetuximab IV over 60-120 minutes once weekly.
  • Arm II: Patients receive oral placebo once daily and cetuximab IV over 60-120 minutes once weekly.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Tumor tissue and blood samples are collected for correlative studies. Samples are analyzed for biomarker levels (Collagen IV, FGF-2, and epiregulin, amphiregulin, and BRAF mutation status) and correlation with response.

After completion of study treatment, patients are followed at 4 weeks and then every 8 weeks thereafter.

Being tested
cetuximab, brivanib alaninate
Keywords
recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer
Medical subject headings
Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cetuximabBiological

    cetuximab (Erbitux®) - Initial dose - Day 1 (Week 1): 400 mg/m2 IV over 120 minutes Maintenance Infusions (subsequent weeks): 250 mg/m2 IV over 60 minutes

  • brivanib alaninateDrug

    brivanib (BMS-582664) 800 mg po, QD

Study groups in NCT00640471
Study groupRoleWhat they receive
BrivanibActive comparatorNot described
Receives: Biological: cetuximab; Drug: brivanib alaninate
PlaceboActive comparatorNot described
Receives: Biological: cetuximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival

    Measured: 3 years

Secondary outcomes (8)

  1. Progression-free survival

    Measured: 3 years

  2. Objective response rate

    Measured: 3 years

  3. Duration of response

    Measured: 3 years

  4. Quality of life (using EORTC QLQ-C30 and Skindex-16 Dermatology Survey)

    Measured: 3 years

  5. Health utilities (using HUI3 Health Utilities Index)

    Measured: 3 years

  6. Economic evaluation

    Measured: 3 years

  7. Safety profile

    Measured: 3 years

  8. Molecular markers

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2008 (estimated)
  2. Study start12 May 2008
  3. Primary completion6 Sep 2011
  4. Study completion10 Jan 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
750 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00640471
Sponsor's protocol ID
CO20
Other IDs
CAN-NCIC-CO20, CDR0000590316
Status last verified
Apr 2020
First submitted
20 Mar 2008
Last updated
4 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Quality of life (QoL) assessment in patients (pts) with K-RAS wild-type (WT) chemotherapy refractory metastatic colorectal cancer (mCRC) treated with cetuximab (CET) plus brivanib alaninate (BRIV) or placebo: Results of the NCIC Clinical Trials Group and AGITG CO.20 trial. J Clin Oncol 30, 2012 (suppl 4; abstr 542). Jolie Ringash, Heather-Jane Au, Lillian L. Siu, Jeremy D. Shapiro, Derek J. Jonker, John Raymond Zalcberg, Malcolm J. Moore, Andrew H. Strickland, Rami Kotb, Mark Jeffery, Thierry Alcindor, Siobhan Ng, Muhammad Salim, Sabe S. Sabesan, Jacob C. Easaw, Jennifer Anne Shannon, Fabyolla El-Tahche, Ian B. Walters, Dongsheng Tu, Christopher J. O'Callaghan.

  • Phase III randomized trial of cetuximab (CET) plus either brivanib alaninate (BRIV) or placebo in patients (pts) with metastatic (MET) chemotherapy refractory K-RAS wild-type (WT) colorectal carcinoma (CRC): The NCIC Clinical Trials Group and AGITG CO.20 trial. J Clin Oncol 30, 2012 (suppl 4; abstr 386). Lillian L. Siu, Jeremy D. Shapiro, Derek J. Jonker, Christos Stelios Karapetis, John Raymond Zalcberg, John Simes, Felix Couture, Malcolm J. Moore, Timothy Jay Price, Jehan Siddiqui, Louise M. Nott, Danielle Charpentier, Winston S. Liauw, Michael B. Sawyer, Michael Jefford, Nadine M Magoski, Andrew Mark Haydon, Ian B. Walters, Dongsheng Tu, Christopher J. O'Callaghan.

  • Final analysis of the phase III randomized trial of cetuximab (CET) plus either brivanib alaninate (BRIV) or placebo in patients (pts) with chemotherapy refractory, K-RAS wild-type (WT), metastatic colorectal carcinoma (mCRC): The NCIC Clinical Trials Group and AGITG CO.20 trial. J Clin Oncol 30, 2012 (suppl; abstr 3504). Lillian L. Siu, Jeremy David Shapiro, Derek J. Jonker, Christos Stelios Karapetis, John Raymond Zalcberg, John Simes, Felix Couture, Malcolm J. Moore, Timothy Jay Price, Jehan Siddiqui, Louise M. Nott, Danielle Charpentier, Winston S. Liauw, Michael B. Sawyer, Michael Jefford, Nadine M Magoski, Andrew Mark Haydon, Ian B. Walters, Dongsheng Tu, Christopher J. O'Callaghan.

  • Analysis of plasma biomarkers potentially associated with antiangiogenic resistance in NCIC CTG/AGITG CO.20: A phase III randomized trial of cetuximab (CET) plus either brivanib alaninate (BRIV) or placebo in patients (pts) with chemotherapy refractory, k-RAS wild-type (WT), metastatic colorectal carcinoma (mCRC). J Clin Oncol 30, 2012 (suppl; abstr 3572). Jeremy David Shapiro, Lillian L. Siu, Christopher J O'Callaghan, John Raymond Zalcberg, Malcolm J. Moore, Timothy Jay Price, Catherine Doyle, John Simes, Brian Peter Findlay, Michelle F. Cronk, Asif Shaikh, Warren Lance Joubert, Benoit Samson, Antonino Bonaventura, Craig Underhill, David Wyld, Ian B. Walters, Penny Phillips, Dongsheng Tu, Derek J. Jonker.

  • Siu LL, Shapiro JD, Jonker DJ, Karapetis CS, Zalcberg JR, Simes J, Couture F, Moore MJ, Price TJ, Siddiqui J, Nott LM, Charpentier D, Liauw W, Sawyer MB, Jefford M, Magoski NM, Haydon A, Walters I, Ringash J, Tu D, O'Callaghan CJ. Phase III randomized, placebo-controlled study of cetuximab plus brivanib alaninate versus cetuximab plus placebo in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal carcinoma: the NCIC Clinical Trials Group and AGITG CO.20 Trial. J Clin Oncol. 2013 Jul 1;31(19):2477-84. doi: 10.1200/JCO.2012.46.0543. Epub 2013 May 20.

    PubMed 23690424

  • Nicholls DL, Xu MC, Zhan L, Sharma D, Hueniken K, Chiasson K, Wahba M, Brown MC, Grant B, Shapiro J, Karapetis CS, Simes J, Jonker D, Tu D, O'Callaghan C, Chen E, Liu G. Machine Learning Models of Early Longitudinal Toxicity Trajectories Predict Cetuximab Concentration and Metastatic Colorectal Cancer Survival in the Canadian Cancer Trials Group/AGITG CO.17/20 Trials. JCO Clin Cancer Inform. 2025 Apr;9:e2400114. doi: 10.1200/CCI.24.00114. Epub 2025 Apr 11.

    PubMed 40215447

  • Hay AE, Pater JL, Corn E, Han L, Camacho X, O'Callaghan C, Chong N, Bell EN, Tu D, Earle CC. Pilot study of the ability to probabilistically link clinical trial patients to administrative data and determine long-term outcomes. Clin Trials. 2019 Feb;16(1):14-17. doi: 10.1177/1740774518815653. Epub 2018 Nov 22.

    PubMed 30466310

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing cetuximab and brivanib alaninate in people with Colorectal Cancer, run by NCIC Clinical Trials Group at 37 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (time frame: 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00640471, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2023.

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