CALIBRATION
Research type
Research Study
Full title
Cambridge, single centre, prospective, exploratory biomarker study to assess early changes in circulating tumour DNA and characterise tumour profiling in patients with oesophageal malignancies and advanced solid tumours, receiving MEDI4736 (Durvalumab), “CALIBRATION”
IRAS ID
_223016
Contact name
Simon Pacey
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust & The University of Cambridge
Eudract number
2017-001719-35
Duration of Study in the UK
3 years, 6 months, 30 days
Research summary
Under physiological conditions, the immune system eliminates potentially malignant cells by a process called "immunologic surveillance" during which T-cell activation is a key step. Some cancer cells can overcome this surveillance by down regulating T-cell function. One of the strategies used by neoplasms to evade the immune system is the expression of "checkpoint inhibitors", such as the Programmed Cell Death receptor 1 ligand (PD-L1). Immunotherapeutic agents (e.g. monoclonal antibodies) are used to block these checkpoints and trigger an immune response to fight cancer. Durvalumab is a type of monoclonal antibody, specifically designed to block PD-L1. Checkpoint inhibitors have been used in the last 7 years and proven to be effective. However, they also cause severe toxicities and are expensive to produce. There is a need to identify a patient population that could potentially benefit from these agents.
Circulating tumour DNA (ctDNA) can be isolated from the plasma, and used as a "liquid biopsy" for its characterization (treatment response, discover new mutations and mechanisms of resistance).
As ctDNA is not yet validated to measure tumour response this exploratory pilot trial will aim to interrogate the role of ctDNA as a response biomarker in patients treated with the PD-L1 inhibitor durvalumab. Patients will be receiving durvalumab and will have their changes in ctDNA level measured and correlated with their radiological tumour response at 6 months to investigate whether tumour responses (responders and non-responders) can be identified early on in treatment using ctDNA rather than waiting for the standard CT scans, which typically show a clinically significant response around 6 months.
The trial will be conducted in one NHS centre in the UK, where nineteen evaluable patients will be evaluated for the primary endpoint.
REC name
London - City & East Research Ethics Committee
REC reference
18/LO/0360
Date of REC Opinion
24 Mar 2018
REC opinion
Unfavourable Opinion