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

Metastatic Breast Cancer Clinical Trial

— BRECOL  

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01733628
• Other study ID #: GEICAM/2011-04
• Secondary ID: GEI-BEV-2011-02
• Status: Completed
• Start date: October 23, 2012
• Est. completion date: December 19, 2017

Study information

• Verified date: December 2019
• Source: Spanish Breast Cancer Research Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This 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 (PFS) (Main endpoint).

The duration of the study will be approximately 42 months.

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 Vascular Endothelial Growth Factor (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 standard BP (Blood Pressure) and Holter recording footage with the PFS. Moreover will be determined in serum, plasma and tumor tissue and certain biomarkers to correlate with efficacy to treatment with bevacizumab.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 143
• Est. completion date: December 19, 2017
• Est. primary completion date: December 19, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. Eastern Cooperative Oncology Group (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 follicle-stimulating hormone (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)

Related Conditions & MeSH terms

• Breast Neoplasms
• Colorectal Neoplasms
• Hypertension
• Metastatic Breast Cancer
• Metastatic Colorectal Cancer

Locations

Country	Name	City	State
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Complejo Hospitalario Universitario Reina Sofía	Córdoba
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Complejo Hospitalario de Jaén	Jaén
Spain	Centro Oncológico MD Anderson	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Fe	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
Spanish Breast Cancer Research Group	Roche Farma, S.A

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With or Without Blood Pressure Increase as a Predictor of Progression Free Survival (PFS)	The incidence of hypertension was studied during treatment with bevacizumab combined with chemotherapy. A Cox regression analysis was performed, entering as a dependent variable the PFS and as independent variable the Arterial Hypertension (AHT) (yes/no). AHT is introduced in the model of Cox as a time-dependent variable since its situation can change as length of the study. The date on which the AHT changes (passes from normotensive to hypertensive).	Up to 3 years
Primary	Progression Free Survival (PFS)	The PFS is the time from the patient receiving the first dose of chemotherapy for advanced disease to the date of progression, the administration of a new antineoplastic treatment that does not contain bevacizumab or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	Up to 3 years
Secondary	Number of Participants With "White Coat" AHT While at Home	The incidence of "white coat" arterial hypertension (AHT) was evaluated comparing each of the measurements in medical attention (in a doctor office) with the measurement that was made at home (without a doctor).; White Coat Hypertension is a phenomenon in which people exhibit a blood pressure level above the normal range, in a clinical setting, though they do not exhibit it in other settings.	Cycle 1, cycle 2, and cycle 3, up to 9 weeks
Secondary	Number of Participants With "White Coat" AHT With 24 Hours Ambulatory BP Measure	The incidence of "white coat" arterial hypertension (AHT) was evaluated comparing each of the measurements with the measurement that was made in the hospital. Ambulatory Blood Pressure Monitoring (ABPM) is when the blood pressure is being measured as patient moves around, living her normal daily life.; White Coat Hypertension is a phenomenon in which people exhibit a blood pressure level above the normal range, in a clinical setting, though they do not exhibit it in other settings.	Baseline, cycle 1, cycle 2, and cycle 3, up to 9 weeks

External Links

•   Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group