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

January 10, 2019 updated by: Spanish Breast Cancer Research Group

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

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

Study Overview

Status

Terminated

Conditions

Detailed Description

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).

Study Type

Observational

Enrollment (Actual)

26

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Málaga, Spain, 29010
        • Hospital Clinico Universitario Virgen de la Victoria

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

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

Description

Inclusion Criteria:

  • patients with breast cancer, at a disseminated stage
  • patients treated with bevacizumab in combination with weekly paclitaxel as first line chemotherapy and who have progressed
  • alive patients authorizing the extraction and analysis of their biological samples.

Exclusion Criteria:

  • patients with a second neoplasia
  • deceased patients
  • patients who have not agreed to participate in the study
  • HER2 positive patients
  • patients with CNS metastases when first treated with bevacizumab in combination with paclitaxel
  • patients with local-regional recurrence only and
  • patients with status NED (resected metastases)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genome-Wide Association Study (GWAS) and microRNA (miRNA) profiling for identification of genetic variants and blood miRNA signatures predictors of bevacizumab response.
Time Frame: 18 months
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
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Spanish Breast Cancer Research Group

Collaborators

Hoffmann-La Roche
Roche Farma, S.A

Investigators

  • Study Director: Study Director, Hospital Clinico Universitario Virgen de la Victoria

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 18, 2012

Primary Completion (Actual)

April 10, 2013

Study Completion (Actual)

April 10, 2013

Study Registration Dates

First Submitted

April 20, 2012

First Submitted That Met QC Criteria

May 14, 2012

First Posted (Estimate)

May 15, 2012

Study Record Updates

Last Update Posted (Actual)

January 14, 2019

Last Update Submitted That Met QC Criteria

January 10, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GEICAM/2011-07 (Other Identifier: GEICAM/2011-07)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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