Tumour Characterisation to Guide Experimental Targeted Therapy
Research type
Research Study
Full title
Tumour Characterisation to Guide Experimental Targeted Therapy (TARGET)
IRAS ID
168337
Contact name
Matthew Krebs
Contact email
Sponsor organisation
The Christie NHS Foundation Trust
Duration of Study in the UK
3 years, 6 months, 0 days
Research summary
Summary of Research
This study proposes to collect blood samples, fresh/archival tumour tissue and other biospecimens (e.g. hair follicles, urine) from patients referred to the Phase I Clinical Trials Unit at The Christie NHS Foundation Trust with:
(I) Advanced solid cancer and limited life expectancy
(II) A rare cancer type where no further standard (or limited) treatment is available.Initially, the feasibility of establishing a pathway for consent, sample collection, storage for genetic analysis and return of results for clinical decision-making within a 28-day timeframe will be determined. Genetic analysis is key to this study. Each cell in the body contains a copy of a person’s genetic code. In cancer cells, distinct faults may arise in this genetic code due to stepwise multiple alterations resulting in uncontrolled cell growth (tumour formation). Genetic analysis of the collected samples will focus on DNA, RNA and/or other molecular abnormalities. Identifying such alterations could be informative for the clinical management of patients diagnosed with advanced solid cancers. A ‘Molecular Tumour Board’ will also be established as part of this initial research phase, with Oncologists, Geneticists, Bioinformaticians and Bioethics to review results and develop recommendations for the disclosure and clinical significance of tumour characterisations.
Once this pathway has been developed, the study aims to consider the analysed tumour information for selecting molecularly targeted phase I clinical trials for the benefit of patients. The ultimate goal is to develop genetic analysis of tumour from blood samples to determine whether future treatment decision pathways can avoid invasive tumour biopsies. These data may also be used for future development of predictive cancer biological markers, the design of clinical trials involving new or existing drugs, discovery of new genetic targets and exploring how resistance to specific anti-cancer agents arises in patients to help improve future cancer treatment management.
Summary of Results
: Every cell in the body contains a copy of an individual’s genetic code which is made up of DNA. Any changes (mutations) within this code may allow cells to grow out of control, which can lead to cancer. This genetic code can be analysed by looking at the DNA in either blood or tumour samples taken from the patient to detect any potential cancer-causing changes.
Looking at these genetic changes is important to allow Doctors to understand which cancer treatments may work best for an individual. In recent years, more treatments have been developed to ‘target’ these genetic changes rather than using a ‘one size fits all’ chemotherapy approach. Targeting treatments to specific changes means fewer cells in the body are impacted meaning there are potentially fewer side effects.
The TARGET (TUMOUR CHARACTERISATION TO GUIDE EXPERIMENTAL TARGETED THERAPY) study was developed to look at whether advanced cancer patients (patients who have exhausted all other treatment options) with any tumour type could be individually matched to a targeted therapy based on the findings from genetic testing on tumour tissue and/or blood samples.
TARGET was developed by staff at The Christie NHS Foundation Trust (The Christie), Cancer Research UK Manchester Institute and The University of Manchester. The study was funded by The Christie Charity, Cancer Research UK and the National Institute for Health and Care Research Biomedical Research Centres. Ethics approval was obtained from North West – Preston Research Ethics Committee.
TARGET had three parts; during part A1 of the study, investigators looked at whether a pathway could be developed to obtain the samples required from patients, send them off for testing then receive genetic results successfully. Part A2 was then initiated to confirm whether the genetic testing results could be used to make clinical decisions to improve patient selection for trials. The results from part A were analysed before investigators initiated part B where the newly established pathways were utilised and the results from the genetic testing were used to make treatment decisions for patients.
Between April 2015 and May 2021 520 patients with advanced solid cancers were recruited at The Christie in Manchester; 100 to part A and 420 to part B. The mean age was 55 (range: 19-81); 293 (56%) were female and 227 (44%) were male. The most common tumour types recruited were colorectal, lung and breast. Patients with rare tumours were also recruited for example rare sarcomas, appendiceal neoplasms, neuroendocrine tumours and carcinoma of unknown primary.
Blood and tissue samples were sent off for all patients for genetic testing following fully informed consent. Information about the patients such as their tumour type, age, medical and family history was collected and recorded in a database. All patients were given a unique identifier upon consent so no staff outside of their own clinical team could identify them.
Following laboratory testing of the samples, results were returned to The Christie and were discussed through a Molecular Tumour Board (MTB) which consisted of clinicians, scientists, bioinformaticians, geneticists among other specialists. The MTB allowed the genetic results to be reviewed and for mutations to be identified to match patients to targeted trials where possible. Trials were considered from across the UK if they were not open to recruitment at The Christie, this gave patients the best possible chance of being matched to a therapy.
Results from part A (the first 100 patients) were published in Nature Medicine in 2019. In this cohort, genetic mutations were identified in 41 patients which had the potential to be targeted with a treatment (actionable mutations); 11 patients went on to receive a targeted therapy based on these results.
TARGET was one of the first studies to demonstrate that ctDNA could be used to successfully match patients to targeted therapies. Some key learnings from the trial were; a large number of patients need to be screened to identify rare mutations, results must be turned around quickly for clinically meaningful decisions to be made (for example, blood results can be returned much more quickly than tumour, primarily due to the amount of time it can take to obtain a tissue sample), it is important to identify suitable trials that are open across the country rather than just one site, and access to good medicines is vital. All of these learnings have been incorporated into a national programme which has been developed and is now open to recruitment across the UK; TARGET National.
A full publication with detailed results from the study is currently being developed.REC name
North West - Preston Research Ethics Committee
REC reference
15/NW/0078
Date of REC Opinion
29 Jan 2015
REC opinion
Favourable Opinion