Clinical trial NCT01733628: Evaluation of Hypertension as a Predictor of Efficacy Bevacizumab in Metastatic Breast Cancer and Colorectal Cancer
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).
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Metastatic Colorectal Cancer
Metastatic Breast Cancer
Keywords: Hypertension
Bevacizumab Response Predictors
Metastatic Breast Cancer
Metastatic Colon Cancer
Lead sponsor: Spanish Breast Cancer Research Group
Sponsor class: OTHER
Collaborators: name: Roche Farma, S.A
First posted: 2012-11-27
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with metastatic (disseminated at the time of diagnosis) breast cancer or colorectal cancer, treated with bevacizumab.

Brief 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.

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 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.

Eligibility 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. 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)

Primary outcomes:
measure: Number of Participants With or Without Blood Pressure Increase as a Predictor of Progression Free Survival (PFS)
timeFrame: Up to 3 years
measure: Progression Free Survival (PFS)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Number of Participants With "White Coat" AHT While at Home
timeFrame: Cycle 1, cycle 2, and cycle 3, up to 9 weeks
measure: Number of Participants With "White Coat" AHT With 24 Hours Ambulatory BP Measure
timeFrame: Baseline, cycle 1, cycle 2, and cycle 3, up to 9 weeks
Other outcomes:
Locations:
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Córdoba
country: Spain
facility: Complejo Hospitalario Universitario Reina Sofía
city: Jaén
country: Spain
facility: Complejo Hospitalario de Jaén
city: Madrid
country: Spain
facility: Centro Oncológico MD Anderson
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Hospital General Universitario de Elche
name: Study Director
role: STUDY_DIRECTOR
References: