Evaluation of Hypertension as a Predictor of Efficacy Bevacizumab in Metastatic Breast Cancer and Metastatic Colorectal Cancer (BRECOL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Spanish Breast Cancer Research Group
Sponsor:
Collaborator:
Roche Farma, S.A
Information provided by (Responsible Party):
Spanish Breast Cancer Research Group
ClinicalTrials.gov Identifier:
NCT01733628
First received: November 20, 2012
Last updated: June 7, 2013
Last verified: June 2013
  Purpose

GEI-BEV-2011-02 is a multicenter, post-authorization observational with prospective follow-up (EPA-SP) study. Will be involved 137 metastatic breast cancer patients or metastatic colorectal cancer. The hypertension will be evaluated as a predictor of efficacy of bevacizumab associated with chemotherapy, in terms of progression-free survival (Main endpoint).

The duration of the study will be approximately 42 months.


Condition
Metastatic Colorectal Cancer
Metastatic Breast Cancer

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: 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).

Resource links provided by NLM:


Further study details as provided by Spanish Breast Cancer Research Group:

Primary Outcome Measures:
  • Blood Pressure [ Time Frame: 3 months after the first blood pressure assessment ] [ Designated as safety issue: No ]

    Blood Pressure will be determined at a baseline, within 14 days before the start of treatment, and on the first day of cycles 1, 2 and 3.

    Measurement tools for recording blood pressure:

    • Holter o Ambulatory Blood Pressure Monitoring
    • Standard Register Blood Pressure following the guidelines of the European Society of Cardiology and Hypertension, 2007


Secondary Outcome Measures:
  • Biomarkers in serum, plasma and tumoral tissue [ Time Frame: 12 months after last patient included finishes the study ] [ Designated as safety issue: No ]

    Evaluate in serum or plasma biomarkers associated with hypertension and angiogenesis [such as placental growth factor (PIGF), the growth factor vascular endothelial dependent (VEGF), the fraction soluble receptor factor vascular endothelial growth (sVEGFR1), interleukin 6 (IL-6) and von Willebrand factor (recognized marker of damage / endothelial dysfunction), among others], and its association with the efficacy to treatment with bevacizumab.

    • Evaluate in tumor tissue biomarkers related to hypertension and angiogenesis (such as genetic variants and differences in the expression levels of VEGF, ARBs, AGTR, among others), and its association with efficacy to treatment with bevacizumab.
    • Evaluate in genomic DNA genetic variants (in genes such as VEGF, VEGFR1, AGTR, AGT, ACE, ADRB1, ADRB2, ADRB3, GNAS, GNB3, etc.) involved in the development of hypertension secondary to treatment with bevacizumab.


Biospecimen Retention:   Samples With DNA

Blood samples (serum or plasma) Tissue samples


Estimated Enrollment: 137
Study Start Date: November 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Detailed Description:

Hypertension (HT) is the most common side effect seen in trials of bevacizumab in combination with chemotherapy. Based on the hypothesis that the development of hypertension during treatment would be an indicative of the successful blockade of the VEGF pathway, different studies have explored retrospectively the relationship between hypertension and the results of treatment with bevacizumab.

This study aims to demonstrate the association between hypertension (diagnosed optimally) with efficacy to treatment with bevacizumab prospectively and secondly verify if blood pressure measures taken at home are a reflection of a diagnosis of hypertension.

Also have been explored different molecular markers involved in the pathway of VEGF which might be used as predictors of response. Therefore, this study includes the collection of blood samples (serum or plasma) and tumor tissue of patients included in this study, with the aim of exploring biomarkers that correlate with treatment efficacy and toxicity.

The diagnosis of hypertension (HT) will be performed using a Holter recording, and standard blood pressure footage will be collected during the first three cycles of treatment given the Common Toxicity Criteria of the National Cancer Institute-NCI CTCAE version 4.0 and the guidelines of the European Society of Cardiology and Hypertension, 2007.

Will be collected a sample of primary tumor and blood for patients who previously have consented it. Samples will be sent to a central laboratory for analysis of biomarkers.

An interim analysis will be conducted to assess the true incidence of hypertension. Based on this analysis, will be evaluated the need to recalculate the sample size.

At the end of the study, will be performed an analysis of correlation of data measured by HTA and Holter recording footage with the SLP standard TA. Moreover will be determined in serum, plasma and tumor tissue and certain biomarkers to correlate with efficacy to treatment with bevacizumab.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with metastatic (disseminated at the time of diagnosis) breast cancer or colorectal cancer, treated with bevacizumab.

Criteria

Inclusion Criteria:

May only participate in the study patients (women and men) who meet all the following criteria:

  1. MCC or MBC patients with chemotherapy and bevacizumab established indication. The first line systemic treatment planned for patients with MCC should be based in combination chemotherapy (oxaliplatin / irinotecan plus fluoropyrimidine) associated with bevacizumab. The first line systemic treatment planned for MBC patients should be based on a combination of paclitaxel or capecitabine plus bevacizumab.
  2. Presence of measurable or evaluable disease according to RECIST 1.1, for the evaluation of the response to treatment.
  3. Equal or more than 18 years old.
  4. ECOG performance status of 0 or 1.
  5. Signed written informed consent.
  6. Women of childbearing potential must have a negative pregnancy test in serum or urine conducted in the 7 days prior to the administration of chemotherapeutic treatment assigned by your doctor, and accept the use of double barrier contraception during the study (Note : Patients who are not of childbearing age may participate without using contraceptives. Women who are of childbearing age are those who: 1) have reached natural menopause (defined as 6 months of spontaneous amenorrhea with serum FSH within postmenopausal interval as determined by the laboratory, or 12 months of spontaneous amenorrhea), 2) have undergone bilateral oophorectomy with or without hysterectomy 6 weeks before, or 3) have undergone bilateral tubal ligation). Men also should use an adequate contraception method.

Exclusion Criteria:

Patients meeting any of the following circumstances will be excluded from the study:

  1. Have received prior systemic anticancer therapy with chemotherapy for advanced disease or prior treatment with bevacizumab.
  2. Treatment with an investigational agent or biological agent within 30 days prior to inclusion in the study.
  3. Contraindications to treatment with chemotherapy and bevacizumab according to summary products characteristics.
  4. Background or current history (within five years before the start of treatment) of other malignancies, except for colorectal carcinoma and breast cancer (patients with basal cell carcinoma or squamous cell skin or cervical carcinoma in situ treated curative may be included in the study).
  5. Life expectancy less than 3 months.
  6. Patients who are pregnant or breastfeeding.
  7. Patients with an inadequate organ function (bone marrow, kidney and liver)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01733628

Contacts
Contact: Eva Carrasco Carrascal +34 6592870 geicam@geicam.org
Contact: Ruth Campo de la Fuente +34 91 6592870 rcampo@geicam.org

Locations
Spain
Corporación Sanitaria Parc Taulí Recruiting
Sabadell, Barcelona, Spain, 08208
Contact: Miguel A. Seguí, PhD., MD.         
Principal Investigator: Miguel A. Seguí, PhD., MD.         
Complejo Hospitalario Universitario A Coruña Recruiting
A Coruña, Spain, 15006
Contact: Lourdes Calvo         
Principal Investigator: Lourdes Calvo         
Hospital Virgen de la Salud Recruiting
Toledo, Spain, 45004
Contact: José I. Chacón, PhD., MD.         
Principal Investigator: José Ignacio Chacón, PhD., MD.         
Hospital Miguel Servet Recruiting
Zaragoza, Spain, 50009
Contact: Antonio Antón, PhD., MD.         
Principal Investigator: Antonio Antón, PhD., MD.         
Sponsors and Collaborators
Spanish Breast Cancer Research Group
Roche Farma, S.A
Investigators
Study Chair: Alvaro Rodríguez Lescure Hospital General Universitario de Elche
  More Information

No publications provided

Responsible Party: Spanish Breast Cancer Research Group
ClinicalTrials.gov Identifier: NCT01733628     History of Changes
Other Study ID Numbers: GEICAM/2011-04, GEI-BEV-2011-02
Study First Received: November 20, 2012
Last Updated: June 7, 2013
Health Authority: Spain: Ethic Committee
Spain: Competent Healt Authority of each Region

Keywords provided by Spanish Breast Cancer Research Group:
Hypertension
Bevacizumab Response Predictors
Metastatic Breast Cancer
Metastatic Colon Cancer

Additional relevant MeSH terms:
Hypertension
Colorectal Neoplasms
Breast Neoplasms
Vascular Diseases
Cardiovascular Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Breast Diseases
Skin Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 22, 2014