Developing a Diagnostic Tool to Predict Response to Chemotherapy
SPAG5
Developing a Diagnostic Tool, Using SPAG5, for Predicting Clinical Benefit From Standard Anthracycline Combination (AC) in Breast Cancer
3 other identifiers
observational
4,750
1 country
1
Brief Summary
Every year nearly 62,000 people are diagnosed with breast cancer in the UK. One in eight women in the UK will develop breast cancer in their lifetime. The investigators are developing an inexpensive test to accurately predict how breast cancer patients will respond to the standard chemotherapy Anthracycline (AC). Only 15-20% of patients have no tumour remaining following AC, so a method of treatment selection is urgently needed. Breast cancers are currently treated with a combination of chemotherapy, targeted therapy and surgery. However, breast cancers are not identical; each tumour's individual characteristics affect how they respond to treatment. Recently the investigators discovered a new tumour characteristic, a protein which is unusually active in approximately 20% of breast cancers. It was found that a patient whose tumour showed high activity often respond well to AC, and vice versa. AC is an aggressive treatment which can potentially cause severe side effects, including a risk of permanent heart damage. It is important, therefore, to spare those patients who will not benefit from AC the physical and emotional side-effects of this drug. Currently, there is no predictive test for selecting which patients will benefit from AC and which will not. The investigators have shown that an accurate prediction can be made by testing the activity of a protein called 'SPerm associated AntiGen 5' (SPAG5) in tumour tissue. The aim is to develop a clinical SPAG5 testing kit that can be used by hospital laboratories to determine the activity of SPAG5 in the tumour. This information will help guide the choice of treatment and achieve better patient outcomes. In June 2018 the investigators started a three year National Institute for Health Research (NIHR) funded project to develop a lab test that could form the basis of a SPAG5 testing kit.
Trial Health
Trial Health Score
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participants targeted
Target at P75+ for all trials
Started Nov 2019
1 active site
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Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 7, 2019
CompletedFirst Submitted
Initial submission to the registry
November 18, 2019
CompletedFirst Posted
Study publicly available on registry
February 20, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 31, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
May 31, 2021
CompletedFebruary 20, 2020
November 1, 2019
1.6 years
November 18, 2019
February 18, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Production of a SPAG5 assay
The primary objective of the study is to deliver a new monoclonal antibody based test that can be used to measure the level of the SPAG5 protein in FFPE breast cancer samples. This objective will only be reached if the new antibodies statistical power, to predict response of breast cancer to chemotherapy, equals or exceeds that of the commercial research grade antibody used in our past publications. The response end points for adjuvant treatment (Surgery then Chemotherapy) will be Relapse Free Survival and Breast Cancer Specific Survival, at 5 and 10 years post treatment. The response end point for neoadjuvant treatment it will be pathological Complete Response at surgery. The delivery of this test will lead to the development of a clinical testing kit that can be used by hospital laboratories, to help guide the choice of treatment and achieve better patient outcomes.
3 years
Secondary Outcomes (1)
Testing of the SPAG5 assay against rival genetic tests
3 years
Study Arms (4)
NUH Adjuvant Breast Cancer Cohort: Historical
This is a series of breast cancer patients treated with adjuvant therapy, who were identified and samples selected for inclusion in the Nottingham Tenovus Breast research project by Prof Ian Ellis's research group (1986-1999; n=1650). The clinical dataset for this cohort of breast cancer patients has been collected in a master clinical database by the team supporting Professor Ian Ellis. The study research team will work with a pseudo-anonymised copy of this dataset.
NUH Adjuvant Breast Cancer Cohort: New
A series of breast cancer patients treated with adjuvant therapy, who were identified and samples selected for inclusion in the Nottingham Tenovus Breast research project by Prof Ian Ellis's research group (2000-2006; n=2000). The clinical dataset for this cohort of breast cancer patients has been collected in a master clinical database by the team supporting Professor Ian Ellis. The study research team will work with a pseudo-anonymised copy of this dataset.
NUH Neoadjuvant Breast Cancer Cohort
For many years clinical data on this cohort of breast cancer patients has been collected in a master clinical database by the clinical team supporting Dr Chan (1996-2021; n=900 patients). This has been used for internal audits and reviews of clinical practice. The study research team will work with a pseudo-anonymised copy of this dataset.
NUH Oncotype DX tested Adjuvant Breast Cancer Cohort
A list of patients tested with Oncotype DX as part of their standard treatment pathway (2015-2021; n=200) will be collected and will form the basis of a master clinical database for this cohort. The database will be managed and populated by the clinical team supporting Dr Chan. The study research team will work with a pseudo-anonymised copy of this dataset.
Interventions
Testing for SPAG5 expression in the tumour.
Eligibility Criteria
This is a retrospective study, involving patients diagnosed with breast cancer. For each patient cohort featured in the study plan we will be using archived patient samples collected as part of each patients standard care pathway. At no point are patients prospectively recruited to the study. Many of these cohorts have already been assembled as part of past projects to construct Tissue Micro Array's (TMA).
You may qualify if:
- Histological diagnosis of primary invasive breast cancer.
- Any hormone receptor status (Oestrogen Receptor, Progesterone Receptor).
- Any Human epidermal growth factor receptor 2 (HER2) receptor status.
- to 90 years old.
You may not qualify if:
- Histological diagnosis of any other cancer type.
- Evidence of distant metastatic disease at diagnosis.
- Insufficient tumour tissue available for research use in tissue blocks held in the NUH Trust pathology archive.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Nottingham University Hospitals NHS Trustlead
- University of Nottinghamcollaborator
- Nottingham Trent Universitycollaborator
- University of Lincolncollaborator
Study Sites (1)
Nottingham University Hospitals NHS Trust
Nottingham, Nottinghamshire, NG5 1PB, United Kingdom
Related Publications (1)
Abdel-Fatah TMA, Agarwal D, Liu DX, Russell R, Rueda OM, Liu K, Xu B, Moseley PM, Green AR, Pockley AG, Rees RC, Caldas C, Ellis IO, Ball GR, Chan SYT. SPAG5 as a prognostic biomarker and chemotherapy sensitivity predictor in breast cancer: a retrospective, integrated genomic, transcriptomic, and protein analysis. Lancet Oncol. 2016 Jul;17(7):1004-1018. doi: 10.1016/S1470-2045(16)00174-1. Epub 2016 Jun 14.
PMID: 27312051RESULT
Related Links
Biospecimen
All tissue used in this study will be stored material which was collected from patients as part of their standard treatment for breast cancer. No new tests or samples are required. This tissue is preserved in a wax block in the hospital pathology archives. It is standard practice at the hospital for patients to consent for any excess tissue, not required for diagnostic purposes, to be left available for use in research. These blocks will be collected and assessed. Those which still have sufficient tissue can be cut in to thin sections (4µm) and stained in the lab to test for the presents of proteins which are important in cancer biology.
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- RETROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 18, 2019
First Posted
February 20, 2020
Study Start
November 7, 2019
Primary Completion
May 31, 2021
Study Completion
May 31, 2021
Last Updated
February 20, 2020
Record last verified: 2019-11
Data Sharing
- IPD Sharing
- Will not share