Study to Evaluate Markers of Response in Locally Advanced Breast Cancer

NCT01338753 | Completed Phase 2 DMC

• 2 other identifiers: ML22197/2009-012009-011037-27
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 11

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.

Conditions

Breast Neoplasms

Keywords

breast; cancer; Pharmacogenomics; bevacizumab

Outcome Measures

Primary Outcomes (13)

• Evaluation of SNPs genotyping.

  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.

  This evaluation will be performed within 14 days before start of treatment

• Assessment of tumoral response by Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI)

  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).

  This evaluation will be performed within 14 days before start of treatment (baseline assesment).

• Assessment of tumoral response by Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI)

  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).

  This evaluation will be performed within 12-19 days after first cycle

• Assessment of tumoral response by Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI)

  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).

  This evaluation will be performed within 12-19 days aftet fifth cycle.

• Positron emission tomography (PET) scan

  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

  This evaluation will be performed within 14 days before start of treatment (baseline assesment)

• Positron emission tomography (PET) scan

  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

  This evaluation will be performed within 12-19 days after first cycle

• Positron emission tomography (PET) scan

  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

  This evaluation will be performed within 12-19 days aftet fifth cycle

• Evaluation of Genomic tissular profile in a sample of biopsy

  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

  This evaluation will be performed within 14 days before start of treatment (baseline assesment

• Evaluation of Genomic tissular profile in a sample of biopsy

  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

  This evaluation will be performed within 12-19 days after first cycle

• Evaluation of Genomic tissular profile in a sample of biopsy

  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).

  This evaluation will be performed within 12-19 days aftet fifth cycle

• Evaluation of Proteomic expression in blood serum

  To determine the proteomic expression in blood serum, a ZeptoMARK Reverse Array assay will be performed according to manufacturer's instructions.

  This evaluation will be performed within 14 days before start of treatment (baseline assesment)

• Evaluation of Proteomic expression in blood serum

  To determine the proteomic expression in blood serum, a ZeptoMARK Reverse Array assay will be performed according to manufacturer's instructions.

  This evaluation will be performed within 12-19 days after first cycle. Description:

• Evaluation of Proteomic expression in blood serum

  To determine the proteomic expression in blood serum, a ZeptoMARK Reverse Array assay will be performed according to manufacturer's instructions.

  This evaluation will be performed within 12-19 days aftet fifth cycle.

Secondary Outcomes (1)

• Evaluation of Complete pathological response in surgical piece

  This evaluation will be performed within 20-22 weeks after start of treatment.

Interventions

Bevacizumab, docetaxel and doxorubicin followed by surgery OTHER

The dosage form is Parenteral Injection (I/V) for all study drugs. Bevacizumab 15mg/kg in a single dose on day 1. Then 3 weeks later begin the cycles. On the day 1 of the cycle the patient receives Bevacizumab 15mg/kg, docetaxel 60mg/m2 and doxorubicin 50mg/m2. The cycles have a frequency of one every three weeks, and the protocol defines 4 cycles in total. The surgical procedure will be done 4-6 weeks after completion of chemotherapy.

Also known as: Avastin, Taxotere, Adriamycin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female
• Signed Informed consent form
• Ages between 18 and 70
• 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

You may not qualify if:

• Metastatic disease
• Inadequate health to receive the study chemotherapy
• Previous breast cancer treatment
• Pregnant or lactating women
• 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
• 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
• Chronical corticosteroid treatment
• Hypersensitivity reaction to bevacizumab or any of its components or any of the other study drugs or components

Sponsors & Collaborators

• Clinica Universidad de Navarra, Universidad de Navarra: lead
• Roche Farma, S.A: collaborator

Study Sites (11)

Hospital Obispo Polanco

Teruel, Aragon, 44002, Spain

Location

Hospital Miguel Servet

Zaragoza, Aragon, 50009, Spain

Location

Hospital General Yagüe

Burgos, Burgos, 09005, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital de Donosti

San Sebastián, Guipúzcoa, 20014, Spain

Location

Onkologikoa

San Sebastián, Guipúzcoa, 20014, Spain

Location

Hospital de San Millan

Logroño, La Rioja, 26006, Spain

Location

Clinica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital de Tudela

Tudela, Navarre, 31500, Spain

Location

Hospital de Basurto

Bilbao, Vizcaya, 48013, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms

Interventions

Bevacizumab; Docetaxel; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Antonio Anton, MD

  Hospital Miguel Servet

  PRINCIPAL INVESTIGATOR

• Jesus Garcia-Foncillas, MD

  Clinica Universitaria de Navarra

  PRINCIPAL INVESTIGATOR

• Alfonso Yubero, MD

  Hospital Obispo Polanco

  PRINCIPAL INVESTIGATOR

• Isabel Alvarez, MD

  Hospital Donosti

  PRINCIPAL INVESTIGATOR

• Jose Manuel Lopez-Vega, MD

  Hospital Universitario Marqués de Valdecilla

  PRINCIPAL INVESTIGATOR

• Blanca Hernando, MD

  Hospital General Yagüe

  PRINCIPAL INVESTIGATOR

• Jose Juan Illarramendi, Md

  Hospital de Navarra

  PRINCIPAL INVESTIGATOR

• Irene Gil, MD

  Hospital de Tudela

  PRINCIPAL INVESTIGATOR

• Purificacion Martinez del Prado, MD

  Hospital de Basurto

  PRINCIPAL INVESTIGATOR

• Rosa Sanchez, MD

  Complejo Hospitalario San Millán San Pedro De La Rioja

  PRINCIPAL INVESTIGATOR

• Arrate Plazaola, MD

  Onkologikoa

  PRINCIPAL INVESTIGATOR

• Serafin Morales, MD

  Hospital Universitario Arnau Vilanova de Lleida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2011
• First Posted: April 19, 2011
• Study Start: October 1, 2009
• Primary Completion: October 1, 2010
• Study Completion: May 1, 2011
• Last Updated: September 10, 2013

Record last verified: 2013-09

Locations

ES (11)