Study to Evaluate Markers of Response in Locally Advanced Breast Cancer

Phase 2

Completed

• Conditions: Breast Neoplasms

• Registration Number: NCT01338753
• Lead Sponsor: Clinica Universidad de Navarra, Universidad de Navarra

Brief Summary

The purpose of this study is to compare the association between image and certain molecular markers with complete response in patients with locally advanced breast cancer, treated with neoadjuvant chemotherapy composed of Bevacizumab, Docetaxel and Doxorubicin.

Detailed Description

This is a pharmacogenomic phase II, multicenter, prospective clinical trial whose main objective is to evaluate the association of molecular and imaging markers with the response to bevacizumab administration in combination with docetaxel and doxorubicin as neoadjuvant chemotherapy in patients diagnose with locally advanced breast cancer.

Study Timeline

• Study Start: 2009-10
• Primary Completion: 2010-10
• Study First Submitted: 2011-03-04
• Study First Submitted QC: 2011-04-18
• Study First Posted: 2011-04-19
• Study Completion: 2011-05
• Status Verified: 2013-09
• Last Update Submitted: 2013-09-09
• Last Update Posted: 2013-09-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 74

Inclusion Criteria

• Female
• Signed Informed consent form
• Ages between 18 and 70
• 12 months of life expectancy at least
• Histologically confirmed breast cancer
• No previous treatment for locally advanced breast cancer
• Her2+ o Her2-
• Disease measurable by PET and/or MRI
• ECOG 0-1
• Adequate organic function
• Negative pregnancy test; fertile women must use anticonceptive methods after ICF and 30 days after last study drug administration
• Enough capability to follow the procedures and follow-up test included in the protocol

Exclusion Criteria

• Metastatic disease
• Inadequate health to receive the study chemotherapy
• Previous breast cancer treatment
• Pregnant or lactating women
• Major surgery or significative traumatic injure in the 28 days previous to inclusion, or during treatment.
• Minor surgery 24 hours before first bevacizumab infusion
• Concomitant or recent aspirin(>325mg/day)or clopidogrel(>75mg/day) treatment
• Concomitant or recent oral anticoagulant treatment
• History or evidence or bleeding diathesis or hereditary coagulopathy with bleeding risk
• Uncontrolled arterial hypertension
• Clinical significative heart disease, or uncontrolled severe arrhythmia disorder
• Unhealed wounds, peptic ulcer or bone fracture
• History of abdominal fistula, gastrointestinal perforation or intrabdominal abscess, 6 months before inclusion
• Evidence of any other disease, neurological or metabolical disorder or physical examination or laboratory finding related with any disease that makes the subjet ineligible for the study treatment or that put the subject in risk because of the study treatment.
• Psychiatric disorders that may prevent the subject to complete the study treatment
• Current participation in any other trial involving an investigational drug, or participation in any kind of trial 28 days before inclusion
• Chronical corticosteroid treatment
• Hypersensitivity reaction to bevacizumab or any of its components or any of the other study drugs or components
• Patients diagnosed with different neoplasms the previous 5 years excluding non melanoma skin cancer and resected cervical cancer

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Evaluation of SNPs genotyping.	This evaluation will be performed within 14 days before start of treatment	The analysis of genetic differences will be determined through analysis of single nucleotide polymorphisms. It will be assesed before starting the treatment using Affymetrix's Human Mapping 500k array set.
Assessment of tumoral response by Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI)	This evaluation will be performed within 12-19 days aftet fifth cycle.	The radiological interpretation of the images will evaluate size, shape, extent, distribution and kinetics of the lesons according to American College of Radiology Breast Imaging Reporting and Data System (ACR BIRADS- MRI (2003) guidelines).
Positron emission tomography (PET) scan	This evaluation will be performed within 12-19 days aftet fifth cycle	It will be determined the association between tissue:blood activity ratio and hypoxic tumor volume by 18F-fluoromisonidazole positron emission tomography (FMISO-PET). DNA synthesis, assesed by \[18F\]-fluoro-3'-deoxy-3'-L-fluorothymidine PET (FLT-PET), will be compared to quantitative kinetics data adquired through previously described DCE-MRI. Finally, these results will be correlated with the Risk Score obtained in the genomic analysis
Evaluation of Genomic tissular profile in a sample of biopsy	This evaluation will be performed within 12-19 days aftet fifth cycle	A correlative analysis will be performed between the expression profile of the sample obtained by Affymetrix 's GeneChip Human Genome U133 and its association with tumor response (based on the imaging markers described previously) on the proposed stages (baseline, before first cycle of treatment and after fifth cycle of treatment).
Evaluation of Proteomic expression in blood serum	This evaluation will be performed within 12-19 days aftet fifth cycle.	To determine the proteomic expression in blood serum, a ZeptoMARK Reverse Array assay will be performed according to manufacturer's instructions.

Secondary Outcome Measures

Name	Time	Method
Evaluation of Complete pathological response in surgical piece	This evaluation will be performed within 20-22 weeks after start of treatment.	To determine if a patient has undergone complete pathological response, an anatomo-pathological study will be conducted on the surgical piece. The evaluation will follow the Miller and Payne criteria; a complete response will be considered just in the absence of invasive tumor cells in breast and lymphatic nodules.

Trial Locations

Locations (11)

Hospital de Tudela; 🇪🇸 Tudela, Navarra, Spain

Hospital de Basurto; 🇪🇸 Bilbao, Vizcaya, Spain

Hospital General Yagüe; 🇪🇸 Burgos, Spain

Hospital de Navarra; 🇪🇸 Pamplona, Navarra, Spain

Hospital Universitario Marqués de Valdecilla; 🇪🇸 Santander, Cantabria, Spain

Clinica Universitaria de Navarra; 🇪🇸 Pamplona, Navarra, Spain

Hospital de Donosti; 🇪🇸 San Sebastián, Guipúzcoa, Spain

Hospital Obispo Polanco; 🇪🇸 Teruel, Aragón, Spain

Hospital Miguel Servet; 🇪🇸 Zaragoza, Aragón, Spain

Onkologikoa; 🇪🇸 San Sebastián, Guipúzcoa, Spain

Hospital de San Millan; 🇪🇸 Logroño, La Rioja, Spain