Clinical trial NCT01377363: Evaluation of Degree of Conversion of HER2 Receptor Between Primary Breast Cancer and Metastasis
Official title: Evaluation of Degree of Conversion of HER2 Receptor Between Primary Breast Cancer and Metastasis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Keywords: metastatic breast cancer
primary breast cancer
Lead sponsor: Spanish Breast Cancer Research Group
Sponsor class: OTHER
Collaborators: name: Roche Farma, S.A
First posted: 2011-06-21
Enrollment: 236
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Female patients diagnosed of primary breast carcinoma with locally recurrent breast carcinoma or metastasic

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.

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

Eligibility 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.

Primary outcomes:
measure: Evaluation of degree of conversion of human epidermal growth factor receptor 2 (HER2) receptor between primary breast cancer and metastases
timeFrame: 2 years since the beginning of the Study
Secondary outcomes:
measure: To determine the probability of changes in ER and PR between different subtypes of primary breast cancer and their metastases
timeFrame: 2 years since beginning of the Study
measure: Analyze the variability in the measurement of HER2, ER and PR between local laboratories and central laboratory
timeFrame: 2 years since the beginning of the Study
measure: Evaluate HER2 conversion rate compared to previously received treatment
timeFrame: 2 years since the beginning of the Study
measure: Evaluate whether the location of biopsied metastases relates to the probability of conversion of HER2.
timeFrame: 2 years since the beginning of the Study
measure: Compare the disease-free survival (DFS) and survival post relapse (SPR) of patients with or without conversion of HER2 and ER/PR
timeFrame: 2 years since the beginning of the Study
measure: Compare the response rate (RR) and time to progression (TTP) for subsequent anti-tumor treatment of patients with or without conversion of HER2
timeFrame: 2 years since the beginning of the Study
measure: 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.
timeFrame: 2 years since the beginning of the Study
measure: Analyze the feasibility of performing biopsies.
timeFrame: 2 years since the beginning of the Study
measure: 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
timeFrame: 2 years since the beginning of the Study
measure: Check if there is any change in the molecular subtypes (luminal, triple negative, HER2) between primary tumors and metastases in patients with HER2 conversion
timeFrame: 2 years since the beginning of the Study
Other outcomes:
Locations:
city: Alcoy
country: Spain
facility: Hospital Virgen de los Lirios
state: Alicante
city: Elda
country: Spain
facility: Hospital General de Elda
state: Alicante
city: Manresa
country: Spain
facility: Althaia Xarxa Asistencial de Manresa
state: Barcelona
city: Castello de la Plana
country: Spain
facility: Consorcio Hospitalario Provincial de Castellón
state: Castellón
city: Algeciras
country: Spain
facility: Hospital Punta de Europa
state: Cádiz
city: Jerez De La Frontera
country: Spain
facility: Hospital Jerez de la Frontera
state: Cádiz
city: Palma De Mallorca
country: Spain
facility: Hospital de Son Llàtzer
state: Islas Baleares
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario de A Coruña
state: La Coruña
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Materno Insular de Canarias
state: Las Palmas
city: Alcorcón
country: Spain
facility: Fundación Hospital Alcorcón
state: Madrid
city: Leganés
country: Spain
facility: Hospital Universitario Severo Ochoa
state: Madrid
city: Pozuelo De Alarcón
country: Spain
facility: Hospital Universitario Quirón salud Madrid
state: Madrid
city: Santa Cruz De Tenerife
country: Spain
facility: Hospital Universitario Nuestra Señora de Candelaria
state: Tenerife
city: Sagunto
country: Spain
facility: Hospital de Sagunto
state: Valencia
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Gerona
country: Spain
facility: Hospital Universitari de Girona Doctor Josep Trueta
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Granada
country: Spain
facility: Hospital Universitario San Cecilio
city: Guadalajara
country: Spain
facility: Hospital Universitario de Guadalajara
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Murcia
country: Spain
facility: Hospital General Universitario Morales Meseguer
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Toledo
country: Spain
facility: Hospital Virgen de la Salud
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Arnau Vilanova
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Hospital Clinico Universitario de Valencia
name: Study Director
role: STUDY_DIRECTOR
affiliation: Consorcio Hospitalario Provincial de Castellon
name: Study Director
role: STUDY_DIRECTOR
References:
citation: de Duenas EM, Hernandez AL, Zotano AG, Carrion RM, Lopez-Muniz JI, Novoa SA, Rodriguez AL, Fidalgo JA, Lozano JF, Gasion OB, Carrascal EC, Capilla AH, Lopez-Barajas IB, Mateu MM, de Ceballos Reyna MH, Ferrando AO, Janez NM, Ballerini VC, Torres AA, Catalan G, Saenz JA, Menjon S, Gonzalez-Angulo AM. Prospective evaluation of the conversion rate in the receptor status between primary breast cancer and metastasis: results from the GEICAM 2009-03 ConvertHER study. Breast Cancer Res Treat. 2014 Feb;143(3):507-15. doi: 10.1007/s10549-013-2825-2. Epub 2014 Jan 11.
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citation: Lluch A, Gonzalez-Angulo AM, Casadevall D, Eterovic AK, Martinez de Duenas E, Zheng X, Guerrero-Zotano A, Liu S, Perez R, Chen K, Chacon JI, Mills GB, Antolin S, Blancas I, Lopez-Serra P, Carrasco E, Caballero R, Prat A, Rojo F, Gonzalez-Perez A, Meric-Bernstam F, Albanell J. Dynamic clonal remodelling in breast cancer metastases is associated with subtype conversion. Eur J Cancer. 2019 Oct;120:54-64. doi: 10.1016/j.ejca.2019.07.003. Epub 2019 Sep 4.
citation: Garcia-Recio S, Thennavan A, East MP, Parker JS, Cejalvo JM, Garay JP, Hollern DP, He X, Mott KR, Galvan P, Fan C, Selitsky SR, Coffey AR, Marron D, Braso-Maristany F, Burgues O, Albanell J, Rojo F, Lluch A, de Duenas EM, Rosen JM, Johnson GL, Carey LA, Prat A, Perou CM. FGFR4 regulates tumor subtype differentiation in luminal breast cancer and metastatic disease. J Clin Invest. 2020 Sep 1;130(9):4871-4887. doi: 10.1172/JCI130323.