Clinical trial NCT03880097: Enabling the Study of Metabolism in Breast Cancer Through Collection of Fresh-tissue Biopsies
Official title: Enabling the Study of Metabolism in Breast Cancer Through Collection of Fresh-tissue Biopsies
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Breast Cancer
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2019-03-19
Enrollment: 240
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women over the age of 18 with a new diagnosis of breast cancer.

Brief summary: This study aims to evaluate how breast cancer cells metabolise nutrients in order to grow. Patients enrolled into this study will undergo a research biopsy that will aim to collect up to 4 cores of tumour tissue. These tissues will then be used in translational research to analyse how specific pro-tumorigenic events change breast cancer cell metabolism (compared to healthy cell metabolism).

Detailed description: Comprehensive analysis linking breast tumour subtypes and their genetic profile with tumour metabolism are required. Traditional model systems are inadequate for this purpose.

1. In vitro models do not represent a true tumour environment and are a subject of prolonged adaptation to artificial cell culture conditions.
2. There is a need for in vivo and ex vivo models representing breast cancer diversity and tumour environment that can be used for predicting and testing the personalised therapies.

Metabolic analysis of fresh tissues (by metabolomics and Mass Spectrometry Imaging (MSI)) and tissues grown as patient derived xenograft models in vivo should reveal the unperturbed relationships between genetic profiles of tumour cells, tumour microenvironment and metabolic profiles of tumours. These relationships should provide new targets for metabolism-based therapies. The experimental systems required to perform this research require fresh breast cancer biopsies.

ENSEMBLE is a prospective multi-centre cohort study that aims to address these issues. Fresh breast tumour tissue will be collected from consented female participants diagnosed with invasive breast cancer, for translational research. Up to 240 participants will be enrolled over a 36-month period and clinical follow-up data will be collected for up to 5 years. Study participants will undergo a "research biopsy" (core biopsy) for translational research that aims to collect up to four cores. The procedure is the same as the standard of care percutaneous core needle biopsy that the patient will have to inform their diagnosis, however, as it is an additional procedure, it is called a "research biopsy". Wherever possible biopsy samples will be taken from the operative specimen at the time of primary surgery however, where neo-adjuvant therapy is planned in a patient's care plan, these patients will undergo a research percutaneous biopsy prior to their surgery, performed either using image-guidance or as a clinical biopsy.

Collected tumour material will be divided: a portion will immediately be frozen in liquid nitrogen, and a portion will be kept fresh. The material will be transported to the primary receiving laboratory at the Francis Crick Institute where part of the sample will be immediately engrafted into immune-deficient mice to create a patient-derived xenograft (PDX) model. The remaining primary samples and samples from PDXs will be used for genomic, metabolomic and other biochemical analyses.

Information about participant demographics, medical history and tumour characteristics will be collected at registration. Participants may be followed up for up to 5 years for clinical outcome data and to clarify information about medical history

Eligibility criteria: Inclusion Criteria:

* Histological diagnosis of newly diagnosed breast cancer
* Known ER and HER2 receptor status
* Tumour diameter ≥1cm on imaging
* Female
* Age 18 or above
* Written informed consent

Exclusion Criteria:

* Previously treated invasive breast cancer
* Primary systemic therapy for breast cancer prior to biopsy
* Oestrogen replacement therapy (HRT) within 14 days of biopsy in ER-positive tumours
* Pregnancy or breastfeeding
* Not considered suitable by clinical team

Primary outcomes:
measure: Number of biopsies collected
timeFrame: 3 years
Secondary outcomes:
measure: Breast cancer cell biology
timeFrame: 5 years
measure: Identifying vulnerabilities in breast cancer cell metabolism
timeFrame: 5 years
Other outcomes:
Locations:
Study officials:
affiliation: University College London Hospitals
name: Neill Patani, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Whittington Hospital
name: Jayant Vaidya, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Michael Douek, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Free London NHS Foundation Trust
name: Amna Sherri, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Barts & The London NHS Trust
name: Laura Johnson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: King's College Hospital NHS Trust
name: Robert Price, MD
role: PRINCIPAL_INVESTIGATOR
References: