IMAGING: Study to Evaluate Markers of Response in Locally Advanced Breast Cancer

Sponsor

Clinica Universidad de Navarra, Universidad de Navarra (Other)

Overall Status

Completed

CT.gov ID

NCT01338753

Collaborator

Roche Farma, S.A (Industry)

Enrollment

Locations

Duration (Months)

6.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms	Other: Bevacizumab, docetaxel and doxorubicin followed by surgery	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

74 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

A Multicenter Phase II Study, to Evaluate the Predictive Markers of Response in Locally Advanced Breast Cancer, Treated With Bevacizumab Combined With Neoadjuvant Chemotherapy

Study Start Date :

Oct 1, 2009

Actual Primary Completion Date :

Oct 1, 2010

Actual Study Completion Date :

May 1, 2011

Outcome Measures

Primary Outcome Measures

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 14 days before start of treatment (baseline assesment).]
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).
Assessment of tumoral response by Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) [This evaluation will be performed within 12-19 days after first 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).
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 14 days before start of treatment (baseline assesment)]
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
Positron emission tomography (PET) scan [This evaluation will be performed within 12-19 days after first 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
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 14 days before start of treatment (baseline assesment]
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 Genomic tissular profile in a sample of biopsy [This evaluation will be performed within 12-19 days after first 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 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 14 days before start of treatment (baseline assesment)]
To determine the proteomic expression in blood serum, a ZeptoMARK Reverse Array assay will be performed according to manufacturer's instructions.
Evaluation of Proteomic expression in blood serum [This evaluation will be performed within 12-19 days after first cycle. Description:]
To determine the proteomic expression in blood serum, a ZeptoMARK Reverse Array assay will be performed according to manufacturer's instructions.
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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Obispo Polanco	Teruel	Aragón	Spain	44002
2	Hospital Miguel Servet	Zaragoza	Aragón	Spain	50009
3	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria	Spain	39008
4	Hospital de Donosti	San Sebastián	Guipúzcoa	Spain	20014
5	Onkologikoa	San Sebastián	Guipúzcoa	Spain	20014
6	Hospital de San Millan	Logroño	La Rioja	Spain	26006
7	Clinica Universitaria de Navarra	Pamplona	Navarra	Spain	31008
8	Hospital de Navarra	Pamplona	Navarra	Spain	31008
9	Hospital de Tudela	Tudela	Navarra	Spain	31500
10	Hospital de Basurto	Bilbao	Vizcaya	Spain	48013
11	Hospital General Yagüe	Burgos		Spain	09005

Sponsors and Collaborators

Clinica Universidad de Navarra, Universidad de Navarra
Roche Farma, S.A

Investigators

Principal Investigator: 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