AURORA: Aiming to Understand the Molecular Aberrations in Metastatic Breast Cancer. (AURORA)

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Procedure: metastatic lesion biopsy

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: AURORA BIG HQ; Email: aurora.bighq@bigagainstbc.org

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Recruiting
    • Institut Jules Bordet
  • Brussels, Belgium, 1200
    • Recruiting
    • Cliniques Universitaires St-Luc
  • Charleroi, Belgium, 6000
    • Recruiting
    • Grand Hopital Charleroi
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
  • Liège, Belgium, 4000
    • Active, not recruiting
    • CHU de Liege
  • Namur, Belgium, 5000
    • Recruiting
    • Clinique et Maternité Sainte-Elisabeth (CMSE - Namur)
• Germany
  • Essen, Germany, 45136
    • Completed
    • Kliniken Essen-Mitte, Klinik für Senologie/ Brustzentrum
  • München, Germany, 80336
    • Active, not recruiting
    • Frauenkliniken Maistrasse-Innenstadt und Großhadern
• Iceland
  • Reykjavík, Iceland, 101
    • Active, not recruiting
    • Landspitali
• Italy
  • Biella, Italy
    • Completed
    • Ospedale degli Infermi - S.O.C.Oncologia
  • Bolzano, Italy, 39100
    • Active, not recruiting
    • Ospedale di Bolzano - Oncologia Medica
  • Carpi, Italy
    • Active, not recruiting
    • Ospedale Ramazzini di Carpi
  • Genova, Italy, 16132
    • Active, not recruiting
    • IRCCS AOU San Martino-IST
  • Legnago, Italy, 37045
    • Active, not recruiting
    • ULSS 21 Legnago
  • Milano, Italy, 20141
    • Active, not recruiting
    • Istituto Europeo di Oncologia
  • Parma, Italy, 43126
    • Active, not recruiting
    • UOC Oncologia Medica - AOU Parma
  • Pavia, Italy
    • Completed
    • Fondazione Salvatore Maugeri
  • Reggio Emilia, Italy
    • Active, not recruiting
    • IRCCS Az Ospedaliera S.Maria Nuova
• Luxembourg
  • Luxembourg, Luxembourg, 1210
    • Active, not recruiting
    • Centre Hospitalier
• Portugal
  • Lisboa, Portugal, 1400-038
    • Recruiting
    • Champalimaud Foundation
• Spain
  • A Coruña, Spain, 15006
    • Recruiting
    • Complexo Hospitalario Universitario A Coruña
  • Barcelona, Spain, 08003
    • Recruiting
    • Hospital del Mar
  • Barcelona, Spain, 08035
    • Active, not recruiting
    • Hospital Vall d'Hebron
  • Barcelona, Spain, 08028
    • Active, not recruiting
    • Dr Rosell Oncology Institute, Quirón Dexeus University Hospital
  • Castellón De La Plana, Spain, 12002
    • Completed
    • Consorcio Hospitalario Provincial de Castellon
  • Cáceres, Spain, 10003
    • Active, not recruiting
    • Hospital San Pedro de Alcantara
  • Lleida, Spain, 25198
    • Active, not recruiting
    • Hospital Universitari Arnau de Vilanova
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Active, not recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28033
    • Active, not recruiting
    • MD Anderson Cancer Center
  • Madrid, Spain, 28050
    • Active, not recruiting
    • Centro Integral Oncologico Clara Campa
  • Sevilla, Spain, 41013
    • Completed
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46010
    • Active, not recruiting
    • Hospital Clinico Universitario de Valencia
  • Valencia, Spain, 46009
    • Recruiting
    • Instituto Valenciano de Oncologia
  • Valencia, Spain, 46014
    • Completed
    • Hospital General Universitario de Valencia
• Sweden
  • Gothenburg, Sweden
    • Active, not recruiting
    • Sahlgrenska University Hospital
  • Jönköping, Sweden, 55185
    • Active, not recruiting
    • Ryhov County Hospital
• Switzerland
  • Baden, Switzerland
    • Completed
    • Kantonsspital Baden
  • Bern, Switzerland
    • Completed
    • Inselspital Bern
  • Chur, Switzerland
    • Completed
    • Kantonsspital Graubuenden
  • Lucerne, Switzerland, 6003
    • Completed
    • Luzerner Kantonsspital, Division of Medical Oncology
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Active, not recruiting
    • Queen Elizabeth Hospital - University Hospitals Birmingham NHS Foundation Trust
  • Bristol, United Kingdom, BS2 8HW
    • Active, not recruiting
    • University Hospitals Bristol NHS Foundation Trust
  • Cardiff, United Kingdom, CF15 7QZ
    • Active, not recruiting
    • Velindre NHS Trust
  • Dundee, United Kingdom, DD1 9SY
    • Active, not recruiting
    • NHS Tayside, Ninewells Hospital
  • Edinburgh, United Kingdom, EH4 2XU
    • Active, not recruiting
    • Edinburgh Cancer Centre - Western General Hospital
  • Glasgow, United Kingdom, G12 0YN
    • Active, not recruiting
    • Beatson West of Scotland Cancer Centre
  • Manchester, United Kingdom
    • Active, not recruiting
    • Christie NHS Foundation Trust
  • Nottingham, United Kingdom
    • Active, not recruiting
    • Nottingham University Hospital NHS Trust
  • Swansea, United Kingdom, SA2 8QA
    • Active, not recruiting
    • Singleton Hospital - ABM University Health Board
  • Truro, United Kingdom, TR1 3LJ
    • Active, not recruiting
    • Royal Cornwall Hospital - Royal Cornwall Hospitals NHS Trust
  • Yeovil, United Kingdom, BA21 4AT
    • Active, not recruiting
    • Yeovil District Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: metastatic lesion biopsy; biopsy of metastatic lesion will be performed at program inclusion or maximum 6 months prior to inclusion. Sample of primary tumor must be available at inclusion.	Procedure: metastatic lesion biopsy; a medical test commonly performed by a surgeon or an interventional radiologist in order to collect tissues for examination; in this case from a metastatic lesion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metastatic Breast Cancer (MBC) understanding	To improve the understanding of locally recurrent/advanced BC and MBC by using high-throughput technologies on primary, metastatic, as well as plasma ctDNA samples, to explore tumor heterogeneity, clonal evolution and transcriptional changes associated with mutational and copy number variation (CNV) patterns.	1 year after end of acrrual

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Building new therapeutic hypotheses	To build new therapeutic hypotheses based on findings generated by Targeted Gene Sequencing (TGS).	1 year after end of accrual and subsequently during follow up period of 10 years
Feasibility of implementing a global molecular screening platform for MBC	To provide evidence that can contribute in assessing the feasibility of implementing a global molecular screening platform of MBC	1 year after end of accrual
Patient identification to match with biomarker-driven clinical trials	To identify patients with candidate driver alterations in their tumors that can be matched to biomarker-driven clinical trials.	on ongoing basis during 3 years' patient recruitment
Identification of "exceptional responders" and "rapid progressors"; the outlier patients	To discover biomarkers of response and/or resistance to systemic therapy using genomic and transcriptomic data of "exceptional responders" and "rapid progressors" (collectively referred to as "outliers", as defined in the AURORA protocol).	1 year after end of accrual and subsequently during follow up period of 10 years
Patients' prognosis determination	To evaluate the prognostic relevance of genomic alterations detected in plasma ctDNA samples, tumor metastatic biopsies and archived primary tissue.	1 year after end of accrual and subsequently during follow up period of 10 years
Correlation between molecular alterations and standardly assessed efficacy endpoints	To correlate molecular alterations in patients with the efficacy endpoints (response rate, progression-free survival and overall survival).	1 year after end of accrual and subsequently during follow up period of 10 years

Collaborators and Investigators

• Sponsor: Breast International Group
• Collaborators: Jules Bordet Institute; Frontier Science & Technology Research Foundation, Inc.
• Investigators: Principal Investigator: Philippe Aftimos, MD, Institut Jules Bordet, Brussels, Belgium; Principal Investigator: Angel Guerrero Zotano, MD, Instituto Valenciano de Oncologia, Valencia, Spain; Principal Investigator: Matteo Benelli, PhD, Breast International Group

Publications and helpful links

Helpful Links

• sponsor's website

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2014
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): March 1, 2031

Study Registration Dates

• First Submitted: March 19, 2014
• First Submitted That Met QC Criteria: March 31, 2014
• First Posted (Estimated): April 2, 2014

Study Record Updates

• Last Update Posted (Actual): July 16, 2025
• Last Update Submitted That Met QC Criteria: July 11, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: breast cancer; biomarker; metastatic; exploratory; molecular screening; Aurora; targeted gene sequencing; molecular aberrations
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: BIG 14-01; 1408-BCG (Other Identifier: EORTC); GBG 85 (Other Identifier: German Breast Cancer Group (GBG)); ICR-CTSU/2014/10050 (Other Identifier: The Institute of Cancer Research, UK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No