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

Study Overview
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Brief Summary
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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.

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

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Procedure: metastatic lesion biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women or men with metastatic or locally relapsed breast cancer manageable with systemic therapy Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1. Written informed consent prior to enrollment into the program. Patient aged ≥ 18 years Patient agrees to provide archived primary tumor tissue Patient agrees to provide newly collected metastatic lesions tissue samples (archived material up to 6 months is allowed provided both Formalin Fixed Paraffin Embedded (FFPE) block and Frozen Tissue are available and were collected from the same lesion at the same time) Patient agrees to provide blood samples 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 Patients with bone-only metastatic disease Patients with brain-only metastatic disease, unless surgical excision is planned (in which case tissue will be collected for AURORA purpose) Known presence of severe hematopoietic, renal, and/or hepatic dysfunction (according to the local PI) Platelet count<100 000/mm3, INR>1.5 (international normalized ratio; blood clotting time) , Albumin<30 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 Any anti-VEGF (vascular endothelial growth factor) or anti-VEGFR (vascular endothelial growth factor receptor) treatment administered less than 4 weeks before new biopsy procedure or no appropriate wash-out period for patients on anticoagulation therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: metastatic lesion biopsy<br>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<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metastatic Breast Cancer (MBC) understanding | To improve the understanding of MBC by performing high coverage Targeted Gene Sequencing (TGS) and RNA sequencing on matched primary and metastatic 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 | 
| Patients' prognosis determination | To evaluate the prognostic relevance of genomic alterations detected in tumor metastatic biopsies and archived primary tissue | 1 year after end of accrual and subsequently during follow up period of 10 years | 
| Identification of exceptional responders and rapid progressors; the outlier patients | To discover biomarkers of response and/or resistance to systemic therapy using genomic and transcriptomics 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 | 
| 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 | 
| 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) set forth in clinical study protocols. | 1 year after end of accrual and subsequently during follow up period of 10 years | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aurora, breast cancer, metastatic, molecular screening, targeted gene sequencing, molecular aberrations, exploratory, biomarker