Evaluation of Degree of Conversion of HER2 Receptor Between Primary Breast Cancer and Metastasis

This study has been completed.
Sponsor:
Collaborator:
Roche Farma, S.A
Information provided by:
Spanish Breast Cancer Research Group
ClinicalTrials.gov Identifier:
NCT01377363
First received: June 8, 2011
Last updated: June 20, 2011
Last verified: June 2011
  Purpose

This is a Prospective Clinical Trial without drugs, to determine the HER2 status in the metastasis of patients with primary breast cancer HER2. 236 patients have been recruited and 32 Sites have been taking part in this Clinical Trial.

Primary Objective:

  • To determine prospectively the probability of stage HER2 conversion between the different subtypes of primary breast cancer (luminal, triple negative and HER2) and their metastasis.

Secondary Objective:

- To determine the probability of changes in ER and PR between different subtypes of primary breast cancer and their metastasis.

  • Analyze the variability in the measurement of HER2, ER and PR between local laboratories and central laboratory.
  • Evaluate HER2 conversion rate compared to previously received treatment.
  • Evaluate whether the location of metastasis biopsied relates to the probability of conversion of HER2.
  • Compare the disease-free survival (DFS) and survival post relapse (SPR) of patients with or without conversion of HER2 and ER/PR.
  • Compare the response rate (RR) and time to progression (TTP) for subsequent anti-tumor treatment of patients with or without conversion of HER2.
  • Analyze the extent to which discrepancies in the HER2 receptor status, ER and PR between the primary tumor and metastasis alter the clinical management of patients.
  • Analyze the feasibility of performing biopsies.
  • Evaluate whether the HER2 status conversion really is associated with activation of intracellular markers of the HER2 signaling pathway: pMAPK, PERK, pAKT, PTEN, PIGF-1R in paired samples (primary tumor and their metastasis).
  • Check if there is any change in the molecular subtypes (luminal, triple negative, HER2) between primary tumors and metastases in patients with HER2 conversion.

Condition
Breast Cancer

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Evaluation of Degree of Conversion of HER2 Receptor Between Primary Breast Cancer and Metastasis

Resource links provided by NLM:


Further study details as provided by Spanish Breast Cancer Research Group:

Primary Outcome Measures:
  • Evaluation of degree of conversion of HER2 receptor between primary breast cancer and metastases [ Time Frame: 2 years since the beginning of the Study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the probability of changes in ER and PR between different subtypes of primary breast cancer and their metastases [ Time Frame: 2 years since beginning of the Study ] [ Designated as safety issue: No ]
    To obtain the contingency table to calculate the probability of changes in ER and PR between different subtypes of primary breast cancers and their metastases.

  • Analyze the variability in the measurement of HER2, ER and PR between local laboratories and central laboratory [ Time Frame: 2 years since the beginning of the Study ] [ Designated as safety issue: No ]
    The contingency table will compare the measurement between the local laboratory in relation to the central laboratory, for each of the HER2 receptor ER and PR (for these two last ones of joint form)

  • Evaluate HER2 conversion rate compared to previously received treatment [ Time Frame: 2 years since the beginning of the Study ] [ Designated as safety issue: No ]
    For each of the types of treatment received will obtain the contingency table that allows to evaluate the conversion rate between the primary tumour HER2 and HER2 for metastases

  • Evaluate whether the location of biopsied metastases relates to the probability of conversion of HER2. [ Time Frame: 2 years since the beginning of the Study ] [ Designated as safety issue: No ]
    The frequency distribution of HER2 conversions according to biopsied metastases sites will be obtained to evaluate the possibility of finding statistically significant differences between them

  • Compare the disease-free survival (DFS) and survival post relapse (SPR) of patients with or without conversion of HER2 and ER/PR [ Time Frame: 2 years since the beginning of the Study ] [ Designated as safety issue: No ]
    Survival curves and disease-free survival post-relapse among patients with and without conversion of HER2 are compared using the log-rank test.In addition, for the analysis of post-relapse survival, also will be analyzed under stratified manner the patients with first metastases and subsequent progression.

  • Compare the response rate (RR) and time to progression (TTP) for subsequent anti-tumor treatment of patients with or without conversion of HER2 [ Time Frame: 2 years since the beginning of the Study ] [ Designated as safety issue: No ]
    To compare statistically response rates and median time to progression (TTP) for patients with and without conversion of HER 2

  • Analyze the extent to which discrepancies in the HER2 receptor status, ER and PR between the primary tumor and metastases alter the clinical management of patients. [ Time Frame: 2 years since the beginning of the Study ] [ Designated as safety issue: No ]
    to obtain contingency tables between the variables HER2, ER and PR in relation to the change variable clinical management of patients and determine their statistical significance

  • Analyze the feasibility of performing biopsies. [ Time Frame: 2 years since the beginning of the Study ] [ Designated as safety issue: No ]
    to obtain the distribution of absolute and relative frequencies for the variable "viability of biopsies (analyzable / not studied)".

  • To evaluate whether the HER2 status conversion really is associated with activation of intracellular markers of the HER2 signaling pathway: pMAPK, pERK, pAKT, pTEN, PIGF-1R in paired samples (primary tumor and their metastases). [ Time Frame: 2 years since the beginning of the Study ] [ Designated as safety issue: No ]
    To obtain contingency tables for each of pMAPK , pERK, pAKT, pTEN, PIGF-1R proteins that relate their condition (+/-) in the primary tumor and metastases in HER2-discordant cases.

  • Check if there is any change in the molecular subtypes (luminal, triple negative, HER2) between primary tumors and metastases in patients with HER2 conversion [ Time Frame: 2 years since the beginning of the Study ] [ Designated as safety issue: No ]
    To obtein contingency tables to evaluate if there is any change of molecular phenotype between primary tumor and metastasis in patients with conversion HER2.Contingency tables will be obtained according to molecular subtype (luminal, triple negative, HER2) and based on molecular markers of the subtype.


Biospecimen Retention:   Samples Without DNA

primary tumor sample and metastasis sample


Enrollment: 236
Study Start Date: December 2009
Groups/Cohorts
Not treatment
Locally recurrent breast carcinoma or metastatic

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Female patients diagnosed of primary breast carcinoma with locally recurrent breast carcinoma or metastasic

Criteria

Inclusion Criteria:

  • Patients who have given their written informed consent to participate in the study.

    • Women over 18 years.
    • Breast cancer locally recurrent or metastatic at first relapse or after successive progressions.
    • Patient has to have available a sample of the primary tumor in paraffin.
    • Patients who are planning for the next 6 weeks, the biopsy (fine needle aspiration / drainage of fluid cavities, open biopsy, core biopsy) of locally recurrent or metastatic lesion [local relapse in the chest wall, nodal , cutaneous or subcutaneous metastases, peripheral lymph nodes and other soft tissues accessible, bone metastases, visceral metastases (lung, liver, brain, etc..) or pleural effusion / ascites / pericardial / cerebrospinal] according to clinical practice center.

Exclusion Criteria:

  • Patients with cognitive impairment that might impede a proper understanding of the written informed consent, according to medical criteria.
  • ipsilateral breast local relapses or contralateral breast away.
  • Patients diagnosed with a second neoplasm, with the exception of cervical carcinoma in situ and non-melanoma skin carcinoma treated properly.
  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: NCT01377363

Sponsors and Collaborators
Spanish Breast Cancer Research Group
Roche Farma, S.A
Investigators
Study Chair: Ana Lluch, MD Hospital Clinico Universitario de Valencia
Study Chair: Eduardo Martinez, MD Consorcio Hospitalario Provincial de Castellon
Principal Investigator: Amparo Oltra, MD Hospital Virgen De los LIrios
Principal Investigator: Antonio Galan, MD Hospital de Sagunto
Principal Investigator: Amparo Ruiz Instituto Valenciano de Oncologia
Principal Investigator: Vicente Carañana, MD Hospital Arnau de Vilanova de valencia
Principal Investigator: Rosa Llorente, MD Hospital Dr. Peset
Principal Investigator: Marian Lavin, MD Hospital La Fé
Principal Investigator: Cristina Llorca, MD Hospital General de Elda
Principal Investigator: Miguel Ruiz, MD Hospital Punta de Europa
Principal Investigator: Manuel Codes, MD Hospital Virgen Macarena
Principal Investigator: Ruben De Toro, MD Hospital de Jerez
Principal Investigator: Isabel Blancas, MD Hospital Clinico San Cecilio de Granada
Principal Investigator: Salomon Manjon, MD University Hospital Virgen de las Nieves
Principal Investigator: Silvia Antolin, MD Complejo Hospitalario Universitario A Coruña
Principal Investigator: Helena López, MD Hospital San Pedro de Alcantara
Principal Investigator: Gustavo Catalan, MD Hospital Son Llàtzer
Principal Investigator: Maria Jo Echarri, MD Hospital Severo Ochoa
Principal Investigator: Ramon Perez, MD Hospital Quiron de Madrid
Principal Investigator: Clara Olier, MD Hospital Universitario Fundación Alcorcón.
Principal Investigator: Noelia Martinez, MD Hospital Universitario Ramón y Cajal
Principal Investigator: José An Garcia, MD Hospital Clinico Universitario San Carlos
Principal Investigator: Adolfo Murias, MD Hospital Materno Insular de Canarias
Principal Investigator: Lioba Ferrera, MD Hospital Nuestra Señora de La Candelaria
Principal Investigator: Alberto Arcediano, MD Hospital General Universitario de Guadalajara
Principal Investigator: Miguel An Cruz, MD Hospital Virgen de la Salud
Principal Investigator: Elisa Garcia, MD Hopsital Morales Meseguer
Principal Investigator: Antonio Antón, MD Hopsital Universitario Miguel Servet
Principal Investigator: Ignacio Tusquets, MD Hospital del Mar
Principal Investigator: Montserrat Muñoz, MD Hospital Clinic i Provincial
Principal Investigator: Joan Dorca, MD Hospital Josep Trueta ICO Girona
Principal Investigator: Ana Miguel, MD Althaia Xarxa Assistencial de Manresa
  More Information

Additional Information:
No publications provided by Spanish Breast Cancer Research Group

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eva Carrasco, MD, Spanish Breast Cancer Research Group
ClinicalTrials.gov Identifier: NCT01377363     History of Changes
Other Study ID Numbers: CONVERTHER/GEICAM 2009-03
Study First Received: June 8, 2011
Last Updated: June 20, 2011
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Spanish Breast Cancer Research Group:
metastatic breast cancer
primary breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on October 01, 2014