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

Overview

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.

Interventions

• 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

Primary outcome measures

• Metastatic Breast Cancer (MBC) understanding [Time frame: 1 year after end of acrrual]

Secondary outcome measures (6)

• Identification of "exceptional responders" and "rapid progressors"; the outlier patients [Time frame: 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 [Time frame: 1 year after end of accrual]
• Patient identification to match with biomarker-driven clinical trials [Time frame: on ongoing basis during 3 years' patient recruitment]
• Building new therapeutic hypotheses [Time frame: 1 year after end of accrual and subsequently during follow up period of 10 years]
• Patients' prognosis determination [Time frame: 1 year after end of accrual and subsequently during follow up period of 10 years]
• Correlation between molecular alterations and standardly assessed efficacy endpoints [Time frame: 1 year after end of accrual and subsequently during follow up period of 10 years]

Eligibility criteria

Inclusion criteria

• 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.
• Written informed consent prior to registration into the program.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
• Availability of primary tumor tissue for research purposes.
• 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.
• 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.
• 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.
• Availability of a whole blood, serum and plasma samples collected at the time of screening.
• 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

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Screening

Study locations

Spain · 15 centers

• Complexo Hospitalario Universitario A Coruña — A Coruña
• Hospital del Mar — Barcelona
• Dr Rosell Oncology Institute, Quirón Dexeus University Hospital — Barcelona
• Hospital Vall d'Hebron — Barcelona
• Consorcio Hospitalario Provincial de Castellón — Castellon
• Hospital San Pedro de Alcantara — Cáceres
• Hospital Universitari Arnau de Vilanova — Lleida
• MD Anderson Cancer Center — Madrid
• … and 7 more centers

United Kingdom · 11 centers

• Queen Elizabeth Hospital - University Hospitals Birmingham NHS Foundation Trust — Birmingham
• University Hospitals Bristol NHS Foundation Trust — Bristol
• Velindre NHS Trust — Cardiff
• NHS Tayside, Ninewells Hospital — Dundee
• Edinburgh Cancer Centre - Western General Hospital — Edinburgh
• Beatson West of Scotland Cancer Centre — Glasgow
• Christie NHS Foundation Trust — Manchester
• Nottingham University Hospital NHS Trust — Nottingham
• … and 3 more centers

Italy · 9 centers

• Ospedale degli Infermi - S.O.C.Oncologia — Biella
• Ospedale di Bolzano - Oncologia Medica — Bolzano
• Ospedale Ramazzini di Carpi — Carpi
• IRCCS AOU San Martino-IST — Genova
• ULSS 21 Legnago — Legnago
• Istituto Europeo di Oncologia — Milan
• UOC Oncologia Medica - AOU Parma — Parma
• Fondazione Salvatore Maugeri — Pavia
• … and 1 more center

Belgium · 6 centers

• Institut Jules Bordet — Brussels
• Cliniques Universitaires St-Luc — Brussels
• Grand Hopital Charleroi — Charleroi
• UZ Leuven — Leuven
• CHU de Liège — Liège
• Clinique et Maternité Sainte-Elisabeth (CMSE - Namur) — Namur

Switzerland · 4 centers

• Kantonsspital Baden — Baden
• Inselspital Bern — Bern
• Kantonsspital Graubuenden — Chur
• Luzerner Kantonsspital, Division of Medical Oncology — Lucerne

Germany · 2 centers

• Kliniken Essen-Mitte, Klinik für Senologie/ Brustzentrum — Essen
• Frauenkliniken Maistrasse-Innenstadt und Großhadern — München

Sweden · 2 centers

• Sahlgrenska University Hospital — Gothenburg
• Ryhov County Hospital — Jönköping

Iceland · 1 center

• Landspitali — Reykjavik

Luxembourg · 1 center

• Centre Hospitalier — Luxembourg

Portugal · 1 center

• Champalimaud Foundation — Lisbon

Identifiers

NCT: NCT02102165 · BIG 14-01 · 1408-BCG · GBG 85 · ICR-CTSU/2014/10050

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗