Clinical trial NCT02102165: AURORA: Aiming to Understand the Molecular Aberrations in Metastatic Breast Cancer.
Official title: AURORA: Aiming to Understand the Molecular Aberrations in Metastatic Breast Cancer.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Metastatic Breast Cancer
Keywords: Aurora
breast cancer
metastatic
molecular screening
targeted gene sequencing
molecular aberrations
exploratory
biomarker
Lead sponsor: Breast International Group
Sponsor class: OTHER
Collaborators: name: Jules Bordet Institute
name: Frontier Science & Technology Research Foundation, Inc.
First posted: 2014-04-02
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

Brief summary: This program initially aims to recruit 1300 breast cancer patients from a large number of hospitals across Europe. Eligible patients are those who are 18 or older, either female or male, and who have not received more than 1 type of treatment from the time metastases were discovered, metastasi(e)s has just been diagnosed or their disease has come back (disease relapse). Biopsy samples from both the primary and metastatic (or relapsed) tumor will be collected for central analyses, together with blood, serum and plasma samples. Any samples not analyzed immediately will be stored in an independent bio-repository to enable future (not yet defined) research aimed at better understanding metastatic breast cancer.

In summary, the main objectives of AURORA are to better understand the genetic aberrations in metastatic breast cancer and to discover the mechanisms of response or resistance to therapy, in order to ultimately identify the "right therapy for each individual patient". At the same time, patients with genetic aberrations that are being targeted by new drugs in development will be offered the possibility to participate in clinical trials, when approved and available in their countries. Ultimately, the aim of AURORA is to improve the outcomes of all patients diagnosed with metastatic breast cancer.


Eligibility criteria: Inclusion Criteria:

1. Female or male ≥ 18 years with diagnosis of locally recurrent/advanced BC not amenable to treatment with curative intent or MBC who have not received more than 1 line of systemic therapy (any type) in the metastatic setting.

   Under protocol 4.0, eligible patients will be limited to locally recurrent/advanced breast cancer not amenable to treatment with curative intent or MBC with:
   * histopathology-confirmed TNBC as defined by ER \<1% and HER2 negative following ASCO-CAP guidelines
   * ILC (either based on ILC morphology or negative E-cadherin expression confirmed by IHC). Mixed ILC/invasive ductal carcinoma are not eligible for the ILC cohort.
   * late relapse BC (any subtype). Late relapse is defined as a patient with a radiologic or histologic confirmation of advanced or MBC relapse \> 10 years from the primary BC diagnosis.
2. Written informed consent prior to registration into the program.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
4. Availability of primary tumor tissue for research purposes.
5. Patient must have a metastatic lesion accessible for biopsy and must agree with the biopsy procedure.

   1. Up until protocol 3.0, up to 100 patients with bone-only metastasis have been included without a metastatic biopsy, if plasma samples have been collected at screening, and if the patient met all other eligibility criteria.
   2. In protocol 4.0, metastatic tumor biopsies from bone lesions will be accepted provided that the chosen site of biopsy was not previously irradiated.
   3. Brain tissue is accepted if it is obtained through surgical excision not planned for AURORA, but as part of the routine clinical practice.
6. The biopsy of the metastatic lesion must be conducted either at the initial diagnosis of the BC relapse before the initiation of 1st line systemic therapy or at the 1st disease progression before initiation of a second line systemic treatment. There is no restriction in the type of therapeutic modality considered as 1st line systemic treatment, which can consist of any type of treatment administered after the diagnosis of the advanced BC relapse till the 1st disease progression thereafter.
7. Biopsies obtained during routine clinical practice are accepted if both formalin-fixed paraffin-embedded (FFPE) and Frozen Tissue (FT) blocks were collected concurrently from the same metastatic lesion and if collected at the pre-specified timelines for AURORA.
8. Availability of a whole blood, serum and plasma samples collected at the time of screening.
9. Patient agrees to provide blood samples at regular intervals, from the screening as well as during the follow-up phase of the program.

Exclusion Criteria:

1. The patient has received more than 1 line of systemic therapy (any type) in the metastatic setting.
2. Patients who have received prior palliative radiotherapy to the only site that is accessible to biopsy.
3. Presence of severe hematopoietic, renal, and/or hepatic dysfunction, including but not restricted to albumin \< 3 g/dl.
4. Known increased risk of hemorrhage during biopsy procedure, as evaluated by the treating physician.
5. Previous or current malignancies of other histologies within the last 5 years, with the exception of in situ carcinoma of the cervix, and adequately treated basal cell or squamous cell carcinoma of the skin.

Primary outcomes:
measure: Metastatic Breast Cancer (MBC) understanding
timeFrame: 1 year after end of acrrual
Secondary outcomes:
measure: Identification of "exceptional responders" and "rapid progressors"; the outlier patients
timeFrame: 1 year after end of accrual and subsequently during follow up period of 10 years
measure: Feasibility of implementing a global molecular screening platform for MBC
timeFrame: 1 year after end of accrual
measure: Patient identification to match with biomarker-driven clinical trials
timeFrame: on ongoing basis during 3 years' patient recruitment
measure: Building new therapeutic hypotheses
timeFrame: 1 year after end of accrual and subsequently during follow up period of 10 years
measure: Patients' prognosis determination
timeFrame: 1 year after end of accrual and subsequently during follow up period of 10 years
measure: Correlation between molecular alterations and standardly assessed efficacy endpoints
timeFrame: 1 year after end of accrual and subsequently during follow up period of 10 years
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Charleroi
country: Belgium
facility: Grand Hopital Charleroi
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHU de Liège
city: Namur
country: Belgium
facility: Clinique et Maternité Sainte-Elisabeth (CMSE - Namur)
city: Essen
country: Germany
facility: Kliniken Essen-Mitte, Klinik für Senologie/ Brustzentrum
city: München
country: Germany
facility: Frauenkliniken Maistrasse-Innenstadt und Großhadern
city: Reykjavík
country: Iceland
facility: Landspitali
city: Biella
country: Italy
facility: Ospedale degli Infermi - S.O.C.Oncologia
city: Bolzano
country: Italy
facility: Ospedale di Bolzano - Oncologia Medica
city: Carpi
country: Italy
facility: Ospedale Ramazzini di Carpi
city: Genova
country: Italy
facility: IRCCS AOU San Martino-IST
city: Legnago
country: Italy
facility: ULSS 21 Legnago
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Parma
country: Italy
facility: UOC Oncologia Medica - AOU Parma
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri
city: Reggio Emilia
country: Italy
facility: IRCCS Az Ospedaliera S.Maria Nuova
city: Luxembourg
country: Luxembourg
facility: Centre Hospitalier
city: Lisboa
country: Portugal
facility: Champalimaud Foundation
city: A Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Dr Rosell Oncology Institute, Quirón Dexeus University Hospital
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Castellón De La Plana
country: Spain
facility: Consorcio Hospitalario Provincial de Castellón
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Centro Integral Oncológico Clara Campa
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: Jönköping
country: Sweden
facility: Ryhov County Hospital
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Lucerne
country: Switzerland
facility: Luzerner Kantonsspital, Division of Medical Oncology
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital - University Hospitals Birmingham NHS Foundation Trust
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust
city: Cardiff
country: United Kingdom
facility: Velindre NHS Trust
city: Dundee
country: United Kingdom
facility: NHS Tayside, Ninewells Hospital
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre - Western General Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Manchester
country: United Kingdom
facility: Christie NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital NHS Trust
city: Swansea
country: United Kingdom
facility: Singleton Hospital - ABM University Health Board
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital - Royal Cornwall Hospitals NHS Trust
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital NHS Foundation Trust
Study officials:
affiliation: Institut Jules Bordet, Brussels, Belgium
name: Philippe Aftimos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto Valenciano de Oncologia, Valencia, Spain
name: Angel Guerrero Zotano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Breast International Group
name: Matteo Benelli, PhD
role: PRINCIPAL_INVESTIGATOR
References: