Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Heart and Blood Diseases

Digestive System Diseases

Breast Neoplasms

Hypertension

Colorectal Neoplasms

Breast Diseases

Skin Diseases

Vascular Diseases

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Herbal and Botanical

Paclitaxel

Albumin-Bound Paclitaxel

Oxaliplatin

Bevacizumab

Irinotecan

Capecitabine

Cola

Patients who received the addition of Bevacizumab (BV) every 2-3 weeks to Chemotherapy (CT) with either oxaliplatin or irinotecan plus fluoropyrimidines in patients with Metastatic Colorectal Cancer (MCRC), either paclitaxel or capecitabine in patients with Metastatic Breast Cancer (MBC), as first-line therapy.

Study Director

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.

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.

Blood samples (serum or plasma) Tissue samples

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

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).

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).

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.

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.

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.

Roche Farma, S.A

Spanish Breast Cancer Research Group

The Safety Population (SP) included 135 patients who signed the Informed Consent and received at least 1 dose of Chemotherapy combined with Bevacizumab.

The Intent to Treat (ITT) Population included 143 patients who signed the Informed Consent.

Serious Adverse Events and/or Other (Not Including Serious) Adverse Events (AEs) have been calculated in the SP (n=135), and All-Cause Mortality have been calculated in the ITT population (n=143) as per protocol.

The Safety Population (SP) included 135 patients who signed the Informed Consent and received at least 1 dose of Chemotherapy combined with Bevacizumab.

The Intent to Treat (ITT) Population included 143 patients who signed the Informed Consent.

Serious Adverse Events and/or Other (Not Including Serious) Adverse Events (AEs) have been calculated in the SP (n=135), and All-Cause Mortality have been calculated in the ITT population (n=143).

Bevacizumab + Chemotherapy

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Spain

Region of Enrollment

ECOG score runs from 0 to 5, with 0 denoting perfect health and 5 death. 0 - Asymptomatic

1. - Symptomatic but completely ambulatory
2. - Symptomatic, \<50% in bed during the day
3. - Symptomatic, \>50% in bed, but not bedbound
4. - Bedbound
5. - Death

Eastern Cooperative Oncology Group (ECOG) status

Blood Pressure Systolic

Blood Pressure Diastolic

Pulse

Only women were assessed for this measure

Women Menopausal Status

Previous arterial hypertension

Cancer type

Scientific Director / Medical Lead / Project Manager

No AHT : 0 to 0.5 years

No AHT : 0.5 to 1 years

No AHT : 1 to 1.5 years

No AHT : 1.5 to 2 years

No AHT : 2 to 2.5 years

No AHT: 2.5 to 3 years

Yes AHT: 0 to 0.5 years

Yes AHT: 0.5 to 1 years

Yes AHT: 1 to 1.5 years

Yes AHT: 1.5 to 2 years

Yes AHT: 2 to 2.5 years

Yes AHT: 2.5 to 3 years

There were 30 patients who were not included in Population per Protocol because of the following: 6 patients didn't fulfil inclusion and exclusion criteria, 8 patients didn't received Bevacizumab, 16 patients didn't have Holter assessment performed at baseline and/or at any other study visit.

Number of Participants With or Without Blood Pressure Increase as a Predictor of Progression Free Survival (PFS)

There were 30 patients who were not included in Population per Protocol because of the following: 6 patients didn't fulfil inclusion and exclusion criteria, 8 patients didn't received Bevacizumab, 16 patients didn't have Holter assessment performed at baseline and/or at any other study visit

Progression Free Survival (PFS)

White coat AHT in cycle 1

White coat AHT in cycle 2

White coat AHT in cycle 3

Number of Participants With "White Coat" AHT While at Home

White coat AHT in baseline

Number of Participants With "White Coat" AHT With 24 Hours Ambulatory BP Measure

Overall Study

GEI-BEV-2011-01 is an Observational multicenter study. The study, involving 200 (100 non-responders and 100 best responders) metastatic breast cancer patients, will search for specific genetic variants (SNPs) and miRNA signatures associated with bevacizumab response. Only patients suffering from metastatic (disseminated at the time of diagnosis) breast cancer, treated with bevacizumab, will be included.

1. -To identify genetic variants as bevacizumab response predictors in metastatic breast cancer
2. To identify miRNA signatures in whole blood as bevacizumab response predictors in metastatic breast cancer patients.

The main endpoint will be progression-free survival (PFS)

The duration of the study will be approximately 18 months

In certain solid neoplasias, antiangiogenic therapies improve response rates and time to progression. However, treatment with antiangiogenic drugs do not improve patient´s overall survival, in addition to being quite toxic and expensive. It is therefore critical to identify reliable predictive factors for drug efficacy and potential toxicity. Pharmacogenomics and pharmacogenetics are emerging as important tools in the optimization of different therapeutic strategies against cancer. Thus, gene expression profiling and genome-wide association studies (GWAS) offer the promise to more effectively tailor individual cancer treatments by identifying new biomarkers for clinical efficacy. They likely represent a real progress in our understanding of cancer as a complex process and an improvement in patient management and treatment. This grant proposal is aimed at: i) identify genetic variants (SNPs) responsible for the different bevacizumab treatment response observed in metastatic breast cancer patients and ii) determine specific blood microRNA (miRNA) signatures associated with the bevacizumab response The reference endpoint for patient selection will be progression free survival (PFS). To increase the statistical significance of the study, patients will be categorized in two groups: non-responders (PFS\<12 weeks) and best responders (PFS\>52 weeks). Blood samples will be drawn prospectively from selected patients, they will be processed to obtain purified total DNA and RNA and, finally, they will be analyzed by next-gen GWAS and miRNA profiling, respectively. DNA samples will be hybridized to ultrahigh density Omni microarrays, containing 2.5 million genetic variants while RNA samples will be hybridized to Affymetrix microarrays containing an up-to-date collection of human miRNA sequences (miRBase v15, 1105 human miRNA probes). Standard computational analysis of both sets of microarray data will performed and the results will be correlated with the main endpoint of the study (PFS).

A Combined GWAS and miRNA for the Identification of Bevacizumab Response Predictors in Metastatic Breast Cancer

A Combined Genome-Wide Association Study (GWAS) and microRNA (miRNA) Profiling Approach for the Identification of Bevacizumab Response Predictors in Metastatic Breast Cancer

Genome-Wide Association Study (GWAS) and microRNA profiling will be performed from DNA and microRNA obtained from blood samples of metastatic breast cancer patients treated with Bevacizumab. Next-generation microarray thecnologies will be performed. Patients will be categorized in two groups: non-responders and best responders. Results of standard computational analysis of microarrays will be correlated with progression free survival data for identification of genetic variants and microRNA signatures predictors of Bevacizumab response

Study title	NCT ID	Conditions	Eligibility	Organization
Evaluation of Hypertension as a Predictor of Efficacy Bevacizumab in Metastatic Breast Cancer and Colorectal Cancer	NCT01733628	Metastatic Colo... Metastatic Brea...	18 Years -	Spanish Breast Cancer Research Group
A Combined GWAS and miRNA for the Identification of Bevacizumab Response Predictors in Metastatic Breast Cancer	NCT01598285	Breast Cancer I...	18 Years -	Spanish Breast Cancer Research Group
Evaluation of Hypertension as a Predictor of Efficacy Bevacizumab in Metastatic Breast Cancer and Colorectal Cancer	NCT01733628	Metastatic Colo... Metastatic Brea...	18 Years -	Spanish Breast Cancer Research Group

Spots Global Cancer Trial Database for bevacizumab response predictors