Evaluation Study of Hypertension as a Predictor of Efficacy Bevacizumab (BV) in Combination With Chemotherapy (CT) in Metastatic Colorectal Cancer (MCC) and Metastatic Breast Cancer (MBC).
Conditions: Metastatic Colorectal Cancer, Metastatic Breast Cancer
Sponsor: Spanish Breast Cancer Research Group

GEICAM/2011-04 (BRECOL) 
 
Study Code: GEI-BEV-2011-02. 
 
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GRUPO ESPAÑOL DE INVESTIGACIÓN EN CÁNCER DE MAMA 
 
 
 
 
 
SPONSOR STUDY CODE: GEICAM/2011-04  
STUDY CODE: GEI-BEV-2011-02 
Version 1: 23rd of February 2012 
 
PROMOTOR:  
GEICAM Foundation (Grupo Español de Investigación en Cáncer de Mama) 
Avenida de los Pirineos 7, oficina 1-14 
28703 San Sebastián de los Reyes (Madrid), Spain 
Phone number: 0034916592870 
Fax: 0034916510406 
Email address: geicam@geicam.org 
 
MEDICAL COORDINATOR INVESTIGATOR: 
Dr. Álvaro Rodríguez Lescure. Hospital General Univ. de Elche, Alicante, Spain. 
Dr. Javier Gallego Plazas. Hospital General Univ. de Elche, Alicante, Spain. 
Dr. Francisco Marín. Hospital Universitario Virgen de la Arrixaca, Murcia, Spain. 
CLINICAL PHASE: Observational Post-authorization study 
CONFIDENTIAL: The information and data included in this protocol contain confidential information that is the property of the 
GEICAM Foundation. No person is authorized to make it public without prior written permission from the GEICAM Foundation. 
These limitations will also apply to all information considered privileged or confidential that will be provided in the future. This 
material may be disclosed and used by your team and collaborators, as necessary to carry out the clinical study. 
 
1. 
STUDY SUMMARY  
 
EVALUATION OF HYPERTENSION AS A PREDICTIVE FACTOR OF 
EFFECTIVENESS BEVACIZUMAB (BV) ASSOCIATED WITH CHEMOTHERAPY 
(CT) IN METASTATIC COLORECTAL CANCER (MCRC) AND METASTATIC 
BREAST CANCER (MBC). 

GEICAM/2011-04 (BRECOL) 
 
Study Code: GEI-BEV-2011-02. 
 
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1.1. 
SPONSOR IDENTIFICATION AND ADDRESS. 
FUNDACIÓN GRUPO ESPAÑOL DE INVESTIGACIÓN EN CÁNCER DE MAMA 
(GEICAM) 
Avenida de los Pirineos 7, Planta 1ª-oficina 1-14 
28703 San Sebastián de los Reyes (Madrid), España 
Telephone number: +34916592870 Fax: +34916510406 
webpage: www.geicam.org 
1.2. 
STUDY TITLE. 
Evaluation of hypertension as a predictive factor of effectiveness Bevacizumab (BV) 
associated with chemotherapy (CT) in Metastatic Colorectal Cancer (MCRC) and Metastatic 
Breast Cancer (MBC).  
 
1.3. 
STUDY CODE. 
GEI-BEV-2011-02 
Sponsor Code: GEICAM/2011-04 
1.4. 
MEDICAL INVESTIGATOR COORDINATOR AND MANAGER. 
Dr. Alvaro Rodríguez Lescure 
 
 
Dr. Javier Gallego Plazas 
Medical Oncology Service 
 
 
Medical Oncology Service 
Hospital General Univ. de Elche 
 
 
Hospital General Univ. de Elche 
Camí de L´Amazara, 11 
 
 
Camí de L´Amazara, 11 
03202 Elche, Alicante (España). 
 
 
03202 Elche, Alicante (España). 
Phone number: +34966616250 
 
 
Phone number: +34966616250 
 
Dr. Francisco Marín 
Cardiology Service 
Hospital Universitario Virgen de la Arrixaca 
Ctra. Madrid-Cartagena s/n 
30120 El Palmar, Murcia (España) 
Phone number: +34968381027 

GEICAM/2011-04 (BRECOL) 
 
Study Code: GEI-BEV-2011-02. 
 
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1.5. 
TYPE OF SITES WHERE THE STUDY IS EXPECTED TO BE PERFORMED. 
The study will be performed in the Medical Oncology Services in Hospitals of the Spanish 
territory.  
1.6. 
ETHIC COMMITTEE (EC) TO EVALUATE. 
The study will be evaluated by the EC of the General Universitary Hospital de Elche. 
1.7. 
OBJECTIVES. 
Primary Objective 
To evaluate the increase in blood pressure (BP) as a predictor of progression-free survival 
(PFS) in patients with metastatic colorectal cancer (MRCC) or metastatic breast cancer 
(MBC) receiving treatment with bevacizumab associated with chemotherapy (CT). 
 
Secondary Objectives 
• 
To evaluate the incidence of "white coat" Hypertension BP (HBP) and its impact on 
the administration of bevacizumab in these patients. 
• 
To evaluate the increase in blood pressure (BP) as a predictor of response in these 
patients. 
 
Exploratory Objectives 
• 
To evaluate in serum or plasma of patients with MRCC or MBC biomarkers related 
to hypertension and angiogenesis [such as placental growth factor (PIGF), vascular 
endothelium-dependent growth factor (VEGF), soluble fraction of the receptor of the 
vascular endothelial growth factor (sVEGFR1), interleukin 6 (IL-6) and von 
Willebrand factor (recognized damage marker / endothelial dysfunction), among 
others), and its association with efficacy to the bevacizumab treatment. 
 
• 
To evaluate in the tumor tissue of patients with MRCC or MBC biomarkers related to 
hypertension and angiogenesis (such as genetic variants and differences in the 
expression levels of VEGF, ARA-II, AGTR, among others), and its association with 
the efficacy to the bevacizumab treatment. 
 
• 
To evaluate in genomic DNA of patients with CCRM or MBC genetic variants (in 
genes such as VEGF, VEGFR1, AGTR, AGT, ACE, ADRB1, ADRB2, ADRB3, 
GNAS, GNB3, among others) involved in the development of hypertension 
secondary to the bevacizumab treatment. 
 

GEICAM/2011-04 (BRECOL) 
 
Study Code: GEI-BEV-2011-02. 
 
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1.8. 
STUDY DESIGN. 
Multicenter study, observational post-authorization with prospective analysis (Prospective 
PASS) of efficacy predictor factors (hypertension), in terms of progression-free survival 
(PFS). 
 
1.9. 
STUDY DISEASE. 
Patients with metastatic colorectal cancer (MRCC) and metastatic breast cancer (MBC) who 
are going to receive a first line of chemotherapy treatment in combination with 
bevacizumab. 
 
1.10. DATA OF THE STUDY MEDICINES. 
Because it is an observational study, the treatment decision will be prior and independent of 
the inclusion of patients in the study and will follow the provisions of the standard of care. 
The planned treatment for patients with MRCC should be based on a combination of 
chemotherapy based on fluoropyrimidines plus bevacizumab. 
The planned treatment for patients with MBC should be based on a combination of 
paclitaxel or capecitabine plus bevacizumab. 
 
1.11. STUDY POPULATION AND TOTAL NUMBER OF PATIENTS. 
This study will include patients (women and men) with metastatic breast cancer (MBC) or 
metastatic colorectal cancer (MCRC) who have not received prior treatment for advanced 
disease and who are candidates for chemotherapy in combination with bevacizumab. 
The expected sample size is 137 patients. 
 
1.12. SCHEDULE: APPROXIMATE DURATION OF THE STUDY. 
The planned schedule is as follows: 
Presentation of the study to the EC: March 2012. 
Recruitment period: approximately 18 months. 
Follow-up Period (after the end of the recruitment): 24 months. 
Estimated date of recruitment completion: December 2013. 
Estimated date of study completion: December 2015. 
 
1.13. FUNDING SOURCE. 
The study sponsor, Fundación Grupo Español de Investigación en Cáncer de Mama 
(GEICAM), assumes the financing of the study in accordance with the guidelines of this 
protocol.  

GEICAM/2011-04 (BRECOL) 
 
Study Code: GEI-BEV-2011-02. 
 
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This financing includes all the research materials, the cost of the registration and control 
processes before the Ethics Committee and health authorities, the design, maintenance and 
management of the database, the fees of the professionals involved in the collection and 
data analysis, the cost derived from the centralized analysis of the samples, the cost of the 
statistical analysis of the information and the reports that are generated. To cover this cost, 
GEICAM will count on the help of Roche Farma S.A.; this support will in any case be 
independent of the results of the study. 
GEICAM guarantees non-interference in case selection process, analysis of the information 
and / or presentation of results, or any other process that may affect the study results.