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

Metastatic Breast Cancer Clinical Trial

— AURORA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02102165
• Other study ID #: BIG 14-01
• Secondary ID: 1408-BCGGBG 85IC
• Status: Recruiting
• Phase: N/A
• Start date: April 2014
• Est. completion date: March 2031

Study information

• Verified date: April 2024
• Source: Breast International Group
• Contact: AURORA BIG HQ
• Email: aurora.bighq[@]bigagainstbc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: March 2031
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

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

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires St-Luc	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Grand Hopital Charleroi	Charleroi
Belgium	UZ Leuven	Leuven
Belgium	CHU de Liège	Liège
Belgium	Clinique et Maternité Sainte-Elisabeth (CMSE - Namur)	Namur
Germany	Kliniken Essen-Mitte, Klinik für Senologie/ Brustzentrum	Essen
Germany	Frauenkliniken Maistrasse-Innenstadt und Großhadern	München
Iceland	Landspitali	Reykjavík
Italy	Ospedale degli Infermi - S.O.C.Oncologia	Biella
Italy	Ospedale di Bolzano - Oncologia Medica	Bolzano
Italy	Ospedale Ramazzini di Carpi	Carpi
Italy	IRCCS AOU San Martino-IST	Genova
Italy	ULSS 21 Legnago	Legnago
Italy	Istituto Europeo di Oncologia	Milano
Italy	UOC Oncologia Medica - AOU Parma	Parma
Italy	Fondazione Salvatore Maugeri	Pavia
Italy	IRCCS Az Ospedaliera S.Maria Nuova	Reggio Emilia
Luxembourg	Centre Hospitalier	Luxembourg
Portugal	Champalimaud Foundation	Lisboa
Spain	Complexo Hospitalario Universitario A Coruña	A Coruña
Spain	Dr Rosell Oncology Institute, Quirón Dexeus University Hospital	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital San Pedro de Alcantara	Cáceres
Spain	Consorcio Hospitalario Provincial de Castellón	Castellón De La Plana
Spain	Hospital Universitari Arnau de Vilanova	Lleida
Spain	Centro Integral Oncológico Clara Campa	Madrid
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	MD Anderson Cancer Center	Madrid
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Instituto Valenciano de Oncología	Valencia
Sweden	Sahlgrenska University Hospital	Gothenburg
Sweden	Ryhov County Hospital	Jönköping
Switzerland	Kantonsspital Baden	Baden
Switzerland	Inselspital Bern	Bern
Switzerland	Kantonsspital Graubuenden	Chur
Switzerland	Luzerner Kantonsspital, Division of Medical Oncology	Lucerne
United Kingdom	Queen Elizabeth Hospital - University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	University Hospitals Bristol NHS Foundation Trust	Bristol
United Kingdom	Velindre NHS Trust	Cardiff
United Kingdom	NHS Tayside, Ninewells Hospital	Dundee
United Kingdom	Edinburgh Cancer Centre - Western General Hospital	Edinburgh
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Christie NHS Foundation Trust	Manchester
United Kingdom	Nottingham University Hospital NHS Trust	Nottingham
United Kingdom	Singleton Hospital - ABM University Health Board	Swansea
United Kingdom	Royal Cornwall Hospital - Royal Cornwall Hospitals NHS Trust	Truro
United Kingdom	Yeovil District Hospital NHS Foundation Trust	Yeovil

Sponsors (3)

Lead Sponsor	Collaborator
Breast International Group	Frontier Science & Technology Research Foundation, Inc., Jules Bordet Institute

Countries where clinical trial is conducted

Belgium,  Germany,  Iceland,  Italy,  Luxembourg,  Portugal,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   sponsor's website