AURORA: Aiming to Understand the Molecular Aberrations in Metastatic Breast Cancer.
- Conditions
- Metastatic Breast Cancer
- Interventions
- Procedure: metastatic lesion biopsy
- Registration Number
- NCT02102165
- Lead Sponsor
- Breast International Group
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1000
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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.
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Written informed consent prior to registration into the program.
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Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
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Availability of primary tumor tissue for research purposes.
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Patient must have a metastatic lesion accessible for biopsy and must agree with the biopsy procedure.
- 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.
- In protocol 4.0, metastatic tumor biopsies from bone lesions will be accepted provided that the chosen site of biopsy was not previously irradiated.
- Brain tissue is accepted if it is obtained through surgical excision not planned for AURORA, but as part of the routine clinical practice.
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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.
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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.
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Availability of a whole blood, serum and plasma samples collected at the time of screening.
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Patient agrees to provide blood samples at regular intervals, from the screening as well as during the follow-up phase of the program.
- The patient has received more than 1 line of systemic therapy (any type) in the metastatic setting.
- Patients who have received prior palliative radiotherapy to the only site that is accessible to biopsy.
- Presence of severe hematopoietic, renal, and/or hepatic dysfunction, including but not restricted to albumin < 3 g/dl.
- Known increased risk of hemorrhage during biopsy procedure, as evaluated by the treating physician.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description metastatic lesion biopsy 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.
- Primary Outcome Measures
Name Time Method Metastatic Breast Cancer (MBC) understanding 1 year after end of acrrual 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.
- Secondary Outcome Measures
Name Time Method Feasibility of implementing a global molecular screening platform for MBC 1 year after end of accrual To provide evidence that can contribute in assessing the feasibility of implementing a global molecular screening platform of MBC
Identification of "exceptional responders" and "rapid progressors"; the outlier patients 1 year after end of accrual and subsequently during follow up period of 10 years 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).
Patients' prognosis determination 1 year after end of accrual and subsequently during follow up period of 10 years To evaluate the prognostic relevance of genomic alterations detected in plasma ctDNA samples, tumor metastatic biopsies and archived primary tissue.
Correlation between molecular alterations and standardly assessed efficacy endpoints 1 year after end of accrual and subsequently during follow up period of 10 years To correlate molecular alterations in patients with the efficacy endpoints (response rate, progression-free survival and overall survival).
Patient identification to match with biomarker-driven clinical trials on ongoing basis during 3 years' patient recruitment To identify patients with candidate driver alterations in their tumors that can be matched to biomarker-driven clinical trials.
Building new therapeutic hypotheses 1 year after end of accrual and subsequently during follow up period of 10 years To build new therapeutic hypotheses based on findings generated by Targeted Gene Sequencing (TGS).
Trial Locations
- Locations (52)
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
MD Anderson Cancer Center
🇪🇸Madrid, Spain
Ospedale di Bolzano - Oncologia Medica
🇮🇹Bolzano, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Institut Jules Bordet
🇧🇪Brussels, Belgium
Cliniques Universitaires St-Luc
🇧🇪Brussels, Belgium
Grand Hopital Charleroi
🇧🇪Charleroi, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
CHU de Liège
🇧🇪Liège, Belgium
Landspitali
🇮🇸Reykjavík, Iceland
Clinique et Maternité Sainte-Elisabeth (CMSE - Namur)
🇧🇪Namur, Belgium
Frauenkliniken Maistrasse-Innenstadt und Großhadern
🇩🇪München, Germany
Kliniken Essen-Mitte, Klinik für Senologie/ Brustzentrum
🇩🇪Essen, Germany
Ospedale degli Infermi - S.O.C.Oncologia
🇮🇹Biella, Italy
Ospedale Ramazzini di Carpi
🇮🇹Carpi, Italy
IRCCS AOU San Martino-IST
🇮🇹Genova, Italy
Fondazione Salvatore Maugeri
🇮🇹Pavia, Italy
UOC Oncologia Medica - AOU Parma
🇮🇹Parma, Italy
ULSS 21 Legnago
🇮🇹Legnago, Italy
IRCCS Az Ospedaliera S.Maria Nuova
🇮🇹Reggio Emilia, Italy
Champalimaud Foundation
🇵🇹Lisboa, Portugal
Centre Hospitalier
🇱🇺Luxembourg, Luxembourg
Complexo Hospitalario Universitario A Coruña
🇪🇸A Coruña, Spain
Hospital San Pedro de Alcantara
🇪🇸Cáceres, Spain
Consorcio Hospitalario Provincial de Castellón
🇪🇸Castellón De La Plana, Spain
Dr Rosell Oncology Institute, Quirón Dexeus University Hospital
🇪🇸Barcelona, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Universitari Arnau de Vilanova
🇪🇸Lleida, Spain
Instituto Valenciano de Oncología
🇪🇸Valencia, Spain
Centro Integral Oncológico Clara Campa
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Sahlgrenska University Hospital
🇸🇪Gothenburg, Sweden
Ryhov County Hospital
🇸🇪Jönköping, Sweden
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Inselspital Bern
🇨🇭Bern, Switzerland
Kantonsspital Baden
🇨🇭Baden, Switzerland
Kantonsspital Graubuenden
🇨🇭Chur, Switzerland
Queen Elizabeth Hospital - University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Luzerner Kantonsspital, Division of Medical Oncology
🇨🇭Lucerne, Switzerland
University Hospitals Bristol NHS Foundation Trust
🇬🇧Bristol, United Kingdom
Edinburgh Cancer Centre - Western General Hospital
🇬🇧Edinburgh, United Kingdom
Velindre NHS Trust
🇬🇧Cardiff, United Kingdom
NHS Tayside, Ninewells Hospital
🇬🇧Dundee, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Singleton Hospital - ABM University Health Board
🇬🇧Swansea, United Kingdom
Nottingham University Hospital NHS Trust
🇬🇧Nottingham, United Kingdom
Royal Cornwall Hospital - Royal Cornwall Hospitals NHS Trust
🇬🇧Truro, United Kingdom
Yeovil District Hospital NHS Foundation Trust
🇬🇧Yeovil, United Kingdom
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain