Tumour Characterisation to Guide Experimental Targeted Therapy - National

Overview

The primary aim of TARGET National is to establish a national framework to offer molecular profiling of circulating tumour DNA and/or tumour tissue (optional) to patients with advanced solid cancers referred to any of the Experimental Cancer Medicine Centres (ECMCs) across the UK, in order to help decision making for allocation to molecularly targeted experimental cancer treatments. Patients will be allocated treatment using a national Molecular Tumour Board to find the most suited therapies based on their molecular profiling results. This study aims to recruit up to 6,000 patients with advanced solid tumours across 5 years and proposes to collect blood samples, archival tumour tissue and fresh tissue (optional) The 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 anticancer agents arises in patients to help improve future cancer treatment management.

Primary outcome measures

• To determine the number of patients matched to a trial of an experimental therapeutic agent based on molecular findings from ctDNA or tumour [Time frame: 5 years]

Secondary outcome measures (6)

• Number of patients and cancer types with successful result obtained from ctDNA. [Time frame: 5 years]
• Turnaround times from date of patient consent to date of genomic tumour profiling report generation. [Time frame: 5 years]
• Number and range of molecular alterations found in blood (and/or tumour) of cancer patients referred to Experimental Cancer Medicine Centres. [Time frame: 5 years]
• Overall response rates of patients who commence on a trial of an experimental therapeutic agent (matched or unmatched) on the basis of molecular findings in this study). [Time frame: 5 years]
• Progression-free survival of patients who commence on a trial of an experimental therapeutic agent (matched or unmatched on the basis of molecular findings in this study). [Time frame: 5 years]
• Overall survival of patients who commence on a trial of an experimental therapeutic agent (matched or unmatched on the basis of molecular findings in this study). [Time frame: 5 years]

Eligibility criteria

Inclusion criteria

• Aged 16 years or over.
• Written informed consent according to GCP and national regulations.
• Patients with confirmed histological or cytological diagnosis of advanced solid cancer who have been referred to any of the ECMCs in the UK AND considered fit enough to receive an experimental therapeutic agent.
• Availability of archival tumour sample (if tumour profiling is required)
• Willingness to provide blood samples during the course of the study if allocated to a matched experimental therapy.

Exclusion criteria

• Known HIV, Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or Hepatitis C virus (defined as HCV RNA detected), due to the difficulties in handling high-risk specimens. Routine testing for hepatitis is not required. Note: Patients with past/resolved Hepatitis B infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen \[anti-HBc\] antibody test) are eligible. Patients with a history of Hepatitis C infection are eligible only if polymerase chain reaction (PCR) analysis is negative for HCV RNA at least 6 months after completing treatment for Hepatitis C infection.
• Known current COVID19 positive (by PCR) or active symptoms for COVID19. Routine testing for COVID19 is not required. Patients with past infection who have fully recovered may be included.
• Patients who are unable to provide fully informed written consent.
• Patients not considered eligible by the investigator for early phase clinical trials.
• Patients currently receiving systemic anti-cancer therapy (due to potential impact on ctDNA analysis), unless patient has clear evidence of progression on hormone-based therapies or tyrosine kinase inhibitors. A minimum of 3 weeks is required post completion of other systemic anti-cancer therapies.
• Presence of any medical, psychological, familial or sociological condition that, in the investigator's opinion, will hamper compliance with the study protocol and follow-up schedule.
• Bleeding diathesis (patients' on anticoagulation are permitted to enter the trial if anticoagulation can be safely managed to enable fresh tumour biopsies and blood sampling).
• Conditions in which research biopsies or blood sampling may increase risk of complications for the patients and/or investigator

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Study design

Observational model

Other

Study locations

United Kingdom · 20 centers

• Queen's University Belfast — Belfast
• University Hospitals Birmingham NHS Foundation Trust — Birmingham
• Cambridge University Hospitals NHS Foundation Trust — Cambridge
• Cardiff University and Velindre Cancer Centre — Cardiff
• Western General Hospital Edinburgh Cancer Centre — Edinburgh
• Beatson West of Scotland Cancer Centre — Glasgow
• St.James's University Hospital — Leeds
• Leicester Cancer Research Centre — Leicester
• … and 12 more centers

Identifiers

NCT: NCT04723316 · CFTSp191

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗