Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01377363
Recruitment Status : Completed
First Posted : June 21, 2011
Last Update Posted : October 15, 2019
Sponsor:
Collaborator:
Roche Farma, S.A
Information provided by (Responsible Party):
Spanish Breast Cancer Research Group

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

Condition or disease
Breast Cancer

Detailed Description:

Population definition: Women previously diagnosed with a primary breast carcinoma who present locally recurrent or metastatic lesions and who meet the selection criteria. The expected sample size is 175 patients.

Observation period: Each patient in the study will be observed from their inclusion in the study until 1 year after the inclusion of the last patient in the study. These visits will match with the scheduled follow-up visits made by the patient according to the usual clinical practice of the site.

Determination of sample size: The calculation of the sample size will be based on determining a number of patients that will achieve the main objective of the study.

The fulfillment of the secondary objectives of the study will be obtained from the size determined by the main objective.

Main objective of the study is to: Prospectively determine the probability of conversion of the HER2 stage between the different subtypes of primary breast cancer (luminal, triple negative and HER2) and their respective metastases.

A review of the literature has allowed to find several published works with varying percentages of HER2 disagreements determined by IHQ + FISH or FISH, which have allowed to estimate an average percentage of disagreements of 10.45% (range between 4% and 20%). Considering the hypothesis that the level of disagreement in each of the different subtypes of primary, luminal, triple negative and HER2 breast cancer, is presented in an approximately similar frequency, that is to say approximately 10.45%.

From the aforementioned data, an average conversion rate to be expected of 10% will be assumed. An alpha risk of 0.05 will be accepted, with an accuracy of +/- 0.09 percentage units, with a bilateral contrast, for which it would be necessary to include 43 patients for each of the three groups mentioned above (luminal, triple negative and HER2), which consequently includes 129 patients. If a loss rate is assumed (patients registered with biopsies finally not performed or not valid, or with inconclusive results or reflecting other diagnoses) of approximately 25%, the necessary size would increase to a total of 172 patients.

Based on these calculations, the final sample size would be 175 patients

Layout table for study information
Study Type : Observational
Actual Enrollment : 236 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Evaluation of Degree of Conversion of HER2 Receptor Between Primary Breast Cancer and Metastasis
Actual Study Start Date : December 11, 2009
Actual Primary Completion Date : November 30, 2012
Actual Study Completion Date : November 30, 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Group/Cohort
Not treatment
Locally recurrent breast carcinoma or metastatic



Primary Outcome Measures :
  1. Evaluation of degree of conversion of human epidermal growth factor receptor 2 (HER2) receptor between primary breast cancer and metastases [ Time Frame: 2 years since the beginning of the Study ]

    The conversion of HER2 is defined as the variation of the HER2 status between the primary tumor and the metastases, both from an initially negative to positive state and from an initially positive to negative state.

    The definition of the different molecular subtypes of primary breast cancer will be the following:

    • Luminal: immunohistochemical phenotype Estrogen Receptor (ER) positive and/or Progesterone Receptor (PR) positive, independently of HER2 status.
    • Triple negative: immunohistochemical phenotype ER negative, PR negative and HER2 negative.
    • HER2: immunohistochemical phenotype ER negative, PR negative and HER2 positive. For the calculation of this probability, a sample of the remnant of the primary tumor and the biopsy of the metastasis, performed according to the usual clinical practice of the site, will be sent to the central laboratory for analysis by immunohistochemistry (IHQ) and in situ hybridization (FISH) analysis.


Secondary Outcome Measures :
  1. 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 ]
    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.

  2. 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 ]
    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)

  3. Evaluate HER2 conversion rate compared to previously received treatment [ Time Frame: 2 years since the beginning of the Study ]
    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

  4. 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 ]
    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

  5. 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 ]
    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.

  6. 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 ]
    To compare statistically response rates and median time to progression (TTP) for patients with and without conversion of HER 2

  7. 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 ]
    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

  8. Analyze the feasibility of performing biopsies. [ Time Frame: 2 years since the beginning of the Study ]
    To obtain the distribution of absolute and relative frequencies for the variable "viability of biopsies (analyzable / not studied)".

  9. Evaluate if the HER2 status conversion is associated with activation of intracellular markers of the HER2 signaling pathway: phosphorylated MAPK (pMAPK), phosphorylated ERK (pERK), phosphorylated AKT (pAKT), PTEN, PIGF-1R in primary tumor and metastases [ Time Frame: 2 years since the beginning of the Study ]
    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.

  10. 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 ]
    To obtain 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


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01377363


Locations
Show Show 32 study locations
Sponsors and Collaborators
Spanish Breast Cancer Research Group
Roche Farma, S.A
Investigators
Layout table for investigator information
Study Director: Study Director Hospital Clinico Universitario de Valencia
Study Director: Study Director Consorcio Hospitalario Provincial de Castellon

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Spanish Breast Cancer Research Group
ClinicalTrials.gov Identifier: NCT01377363    
Other Study ID Numbers: CONVERTHER/GEICAM 2009-03
First Posted: June 21, 2011    Key Record Dates
Last Update Posted: October 15, 2019
Last Verified: October 2019
Keywords provided by Spanish Breast Cancer Research Group:
metastatic breast cancer
primary breast cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases