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

This study has been completed.
Sponsor:
Collaborator:
Roche Farma, S.A
Information provided by (Responsible Party):
Clinica Universidad de Navarra, Universidad de Navarra
ClinicalTrials.gov Identifier:
NCT01338753
First received: March 4, 2011
Last updated: September 9, 2013
Last verified: September 2013
  Purpose

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 Intervention Phase
Breast Neoplasms
Other: Bevacizumab, docetaxel and doxorubicin followed by surgery
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Clinica Universidad de Navarra, Universidad de Navarra:

Primary Outcome Measures:
  • Evaluation of SNPs genotyping. [ Time Frame: This evaluation will be performed within 14 days before start of treatment ] [ Designated as safety issue: No ]
    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) [ Time Frame: This evaluation will be performed within 14 days before start of treatment (baseline assesment). ] [ Designated as safety issue: No ]
    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) [ Time Frame: This evaluation will be performed within 12-19 days after first cycle ] [ Designated as safety issue: No ]
    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) [ Time Frame: This evaluation will be performed within 12-19 days aftet fifth cycle. ] [ Designated as safety issue: No ]
    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 [ Time Frame: This evaluation will be performed within 14 days before start of treatment (baseline assesment) ] [ Designated as safety issue: No ]
    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 [ Time Frame: This evaluation will be performed within 12-19 days after first cycle ] [ Designated as safety issue: No ]
    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 [ Time Frame: This evaluation will be performed within 12-19 days aftet fifth cycle ] [ Designated as safety issue: No ]
    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 [ Time Frame: This evaluation will be performed within 14 days before start of treatment (baseline assesment ] [ Designated as safety issue: No ]
    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 [ Time Frame: This evaluation will be performed within 12-19 days after first cycle ] [ Designated as safety issue: No ]
    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 [ Time Frame: This evaluation will be performed within 12-19 days aftet fifth cycle ] [ Designated as safety issue: No ]
    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 [ Time Frame: This evaluation will be performed within 14 days before start of treatment (baseline assesment) ] [ Designated as safety issue: No ]
    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 [ Time Frame: This evaluation will be performed within 12-19 days after first cycle. Description: ] [ Designated as safety issue: No ]
    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 [ Time Frame: This evaluation will be performed within 12-19 days aftet fifth cycle. ] [ Designated as safety issue: No ]
    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 [ Time Frame: This evaluation will be performed within 20-22 weeks after start of treatment. ] [ Designated as safety issue: No ]
    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.


Enrollment: 74
Study Start Date: October 2009
Study Completion Date: May 2011
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Other: Bevacizumab, docetaxel and doxorubicin followed by surgery

    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.

    Other Names:
    • Avastin
    • Taxotere
    • Adriamycin
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01338753

Locations
Spain
Hospital Obispo Polanco
Teruel, Aragón, Spain, 44002
Hospital Miguel Servet
Zaragoza, Aragón, Spain, 50009
Hospital Universitario Marqués de Valdecilla
Santander, Cantabria, Spain, 39008
Onkologikoa
San Sebastián, Guipúzcoa, Spain, 20014
Hospital de Donosti
San Sebastián, Guipúzcoa, Spain, 20014
Hospital de San Millan
Logroño, La Rioja, Spain, 26006
Hospital de Navarra
Pamplona, Navarra, Spain, 31008
Clinica Universitaria de Navarra
Pamplona, Navarra, Spain, 31008
Hospital de Tudela
Tudela, Navarra, Spain, 31500
Hospital de Basurto
Bilbao, Vizcaya, Spain, 48013
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
  More Information

No publications provided

Responsible Party: Clinica Universidad de Navarra, Universidad de Navarra
ClinicalTrials.gov Identifier: NCT01338753     History of Changes
Other Study ID Numbers: ML22197/2009-01, 2009-011037-27
Study First Received: March 4, 2011
Last Updated: September 9, 2013
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Clinica Universidad de Navarra, Universidad de Navarra:
breast
cancer
Pharmacogenomics
bevacizumab

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bevacizumab
Docetaxel
Liposomal doxorubicin
Doxorubicin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014