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

Primary Purpose

Breast Neoplasms

Status
Completed
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Bevacizumab, docetaxel and doxorubicin followed by surgery
Sponsored by
Clinica Universidad de Navarra, Universidad de Navarra
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Breast Neoplasms focused on measuring breast, cancer, Pharmacogenomics, bevacizumab

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept 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

Sites / Locations

  • Hospital Obispo Polanco
  • Hospital Miguel Servet
  • Hospital Universitario Marqués de Valdecilla
  • Hospital de Donosti
  • Onkologikoa
  • Hospital de San Millan
  • Clinica Universitaria de Navarra
  • Hospital de Navarra
  • Hospital de Tudela
  • Hospital de Basurto
  • Hospital General Yagüe

Outcomes

Primary Outcome Measures

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.
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).
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).
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).
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
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
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
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
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
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).
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.
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.
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.

Secondary Outcome Measures

Evaluation of Complete pathological response in surgical piece
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.

Full Information

First Posted
March 4, 2011
Last Updated
September 9, 2013
Sponsor
Clinica Universidad de Navarra, Universidad de Navarra
Collaborators
Roche Farma, S.A
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1. Study Identification

Unique Protocol Identification Number
NCT01338753
Brief Title
Study to Evaluate Markers of Response in Locally Advanced Breast Cancer
Acronym
IMAGING
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 Type
Interventional

2. Study Status

Record Verification Date
September 2013
Overall Recruitment Status
Completed
Study Start Date
October 2009 (undefined)
Primary Completion Date
October 2010 (Actual)
Study Completion Date
May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Clinica Universidad de Navarra, Universidad de Navarra
Collaborators
Roche Farma, S.A

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Neoplasms
Keywords
breast, cancer, Pharmacogenomics, bevacizumab

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
74 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Other
Intervention Name(s)
Bevacizumab, docetaxel and doxorubicin followed by surgery
Other Intervention Name(s)
Avastin, Taxotere, Adriamycin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Evaluation of SNPs genotyping.
Description
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.
Time Frame
This evaluation will be performed within 14 days before start of treatment
Title
Assessment of tumoral response by Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI)
Description
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).
Time Frame
This evaluation will be performed within 14 days before start of treatment (baseline assesment).
Title
Assessment of tumoral response by Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI)
Description
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).
Time Frame
This evaluation will be performed within 12-19 days after first cycle
Title
Assessment of tumoral response by Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI)
Description
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).
Time Frame
This evaluation will be performed within 12-19 days aftet fifth cycle.
Title
Positron emission tomography (PET) scan
Description
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
Time Frame
This evaluation will be performed within 14 days before start of treatment (baseline assesment)
Title
Positron emission tomography (PET) scan
Description
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
Time Frame
This evaluation will be performed within 12-19 days after first cycle
Title
Positron emission tomography (PET) scan
Description
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
Time Frame
This evaluation will be performed within 12-19 days aftet fifth cycle
Title
Evaluation of Genomic tissular profile in a sample of biopsy
Description
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
Time Frame
This evaluation will be performed within 14 days before start of treatment (baseline assesment
Title
Evaluation of Genomic tissular profile in a sample of biopsy
Description
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
Time Frame
This evaluation will be performed within 12-19 days after first cycle
Title
Evaluation of Genomic tissular profile in a sample of biopsy
Description
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).
Time Frame
This evaluation will be performed within 12-19 days aftet fifth cycle
Title
Evaluation of Proteomic expression in blood serum
Description
To determine the proteomic expression in blood serum, a ZeptoMARK Reverse Array assay will be performed according to manufacturer's instructions.
Time Frame
This evaluation will be performed within 14 days before start of treatment (baseline assesment)
Title
Evaluation of Proteomic expression in blood serum
Description
To determine the proteomic expression in blood serum, a ZeptoMARK Reverse Array assay will be performed according to manufacturer's instructions.
Time Frame
This evaluation will be performed within 12-19 days after first cycle. Description:
Title
Evaluation of Proteomic expression in blood serum
Description
To determine the proteomic expression in blood serum, a ZeptoMARK Reverse Array assay will be performed according to manufacturer's instructions.
Time Frame
This evaluation will be performed within 12-19 days aftet fifth cycle.
Secondary Outcome Measure Information:
Title
Evaluation of Complete pathological response in surgical piece
Description
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.
Time Frame
This evaluation will be performed within 20-22 weeks after start of treatment.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio Anton, MD
Organizational Affiliation
Hospital Miguel Servet
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jesus Garcia-Foncillas, MD
Organizational Affiliation
Clinica Universitaria de Navarra
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alfonso Yubero, MD
Organizational Affiliation
Hospital Obispo Polanco
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Isabel Alvarez, MD
Organizational Affiliation
Hospital Donosti
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jose Manuel Lopez-Vega, MD
Organizational Affiliation
Hospital Universitario Marqués de Valdecilla
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Blanca Hernando, MD
Organizational Affiliation
Hospital General Yagüe
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jose Juan Illarramendi, Md
Organizational Affiliation
Hospital de Navarra
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Irene Gil, MD
Organizational Affiliation
Hospital de Tudela
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Purificacion Martinez del Prado, MD
Organizational Affiliation
Hospital de Basurto
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rosa Sanchez, MD
Organizational Affiliation
Complejo Hospitalario San Millán San Pedro De La Rioja
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Arrate Plazaola, MD
Organizational Affiliation
Onkologikoa
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Serafin Morales, MD
Organizational Affiliation
Hospital Universitario Arnau Vilanova de Lleida
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Obispo Polanco
City
Teruel
State/Province
Aragón
ZIP/Postal Code
44002
Country
Spain
Facility Name
Hospital Miguel Servet
City
Zaragoza
State/Province
Aragón
ZIP/Postal Code
50009
Country
Spain
Facility Name
Hospital Universitario Marqués de Valdecilla
City
Santander
State/Province
Cantabria
ZIP/Postal Code
39008
Country
Spain
Facility Name
Hospital de Donosti
City
San Sebastián
State/Province
Guipúzcoa
ZIP/Postal Code
20014
Country
Spain
Facility Name
Onkologikoa
City
San Sebastián
State/Province
Guipúzcoa
ZIP/Postal Code
20014
Country
Spain
Facility Name
Hospital de San Millan
City
Logroño
State/Province
La Rioja
ZIP/Postal Code
26006
Country
Spain
Facility Name
Clinica Universitaria de Navarra
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hospital de Navarra
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hospital de Tudela
City
Tudela
State/Province
Navarra
ZIP/Postal Code
31500
Country
Spain
Facility Name
Hospital de Basurto
City
Bilbao
State/Province
Vizcaya
ZIP/Postal Code
48013
Country
Spain
Facility Name
Hospital General Yagüe
City
Burgos
ZIP/Postal Code
09005
Country
Spain

12. IPD Sharing Statement

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Study to Evaluate Markers of Response in Locally Advanced Breast Cancer

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