The REGAL Study
Research type
Research Study
Full title
Capturing tRastuzumab rEsistance in Gastroesophageal Adenocarcinoma by Liquid biopsy
IRAS ID
278314
Contact name
Russell Petty
Contact email
Sponsor organisation
Univesrity of Dundee
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Gastroesophageal cancers are a major cause of premature death worldwide – with present treatments 60% of patients die within a year of diagnosis.
Abnormalities in tumour DNA lead to higher than normal levels of the protein HER2 in 20%, promoting faster growth and spread of cancer cells. These HER2 positive cancers are treated with chemotherapy plus trastuzumab, a drug that targets the HER2 protein. But invariably tumours become resistant during treatment, causing cancer relapse within 18 months in the majority. Treatments to overcome trastuzumab resistance and prolong responses are needed.
Some mechanisms of trastuzumab resistance have been identified. However multiple different mechanisms can arise simultaneously and unpredictably, meaning that their detection in individual patients is critical to design personalised strategies to overcome resistance. This is usually achieved by analyzing the DNA of tumour tissue obtained by biopsy. But this procedure is invasive, and often not possible. Recently a new test, liquid biopsy, uses the DNA shed from tumour cells into the bloodstream. Based on a conventional blood draw, this minimally invasive procedure can be repeated during treatment to monitor changes. Several studies have demonstrated liquid biopsies can track the emergence of resistance mechanisms.In REGAL we aim to evaluate the performance of liquid biopsies in detecting the mechanisms of trastuzumab resistance in HER2 positive gastroesophageal cancers. We will analyse shed tumour DNA from blood samples from patients during treatment to identify the mechanisms involved in trastuzumab resistance in individual patients. The clinical relevance of liquid biopsy will be confirmed by comparison with standard tumour tissue biopsy. This study will provide evidence of the feasibility for a follow-on interventional study where liquid biopsy analysis will be used to precisely detect mechanisms of resistance as they emerge and test treatments designed specifically to tackle them and prolong response to trastuzumab.
REC name
East of Scotland Research Ethics Service REC 1
REC reference
20/ES/0090
Date of REC Opinion
29 Oct 2020
REC opinion
Further Information Favourable Opinion