New trial tests whether a targeted drug can help patients with a hard-to-treat cancer

A new clinical trial will test whether a targeted drug can improve outcomes for some patients with cancer of the food pipe and stomach.

Gastrooesphageal adenocarcinoma (GOA) is often diagnosed at a late stage making it more difficult to cure and meaning the cancer often comes back after initial treatment.

Now, the team at the Cancer Research UK Southampton Clinical Trials Unit are running the DECIPHER study with researchers at the University of Oxford to find out if a drug which targets certain markers on the cancer cells can improve outcomes and help stop the cancer returning in certain patients.

A hard-to-treat cancer

Current standard treatment for people with GOA is a course of chemotherapy before having surgery to remove the cancer. This is then followed by further treatment with the same type of chemotherapy.

“This standard treatment, while successful for many patients, doesn’t work for everyone,” says Dr Lizzy Smyth, consultant medical oncologist in upper GI oncology at Oxford University NHS Foundation trust and Chief Investigator of the DECIPHER study. “Most patients who are ctDNA positive, meaning they have fragments of tumour DNA in their blood, will have their cancer return. We hope to improve this with a new and better treatment which has been proven in advanced cancer at an earlier stage."

An alternative treatment?

The DECIPHER study will involve a particular group of patients who are found to be both ctDNA and HER2 positive and will test whether a targeted drug called trastuzumab deruxtecan (T-DXd) could be an alternative treatment for these patients.

ctDNA, or circulating tumour DNA, refers to the presence of small fragments of genetic material from cancer cells which can be detected in the blood stream.

“Recent studies have shown that the likelihood of GOA returning after surgery can be predicted by the presence of ctDNA in the blood,” says Dr Smyth. “Therefore, we can use a simple blood test to identify the patients who are most at risk of relapsing after surgery.”

The treatment in the study, T-DXd, consists of the chemotherapy deruxtecan combined with an antibody called trastuzumab. This antibody attaches to a certain protein on the surface of cells called HER2 and is then taken inside the cell where the chemotherapy drug is activated and destroys the cell from the inside.

Someone who is HER2 positive will have an over-expression of this protein and have lots of HER2 present on the outside of the tumour cells. T-DXd has already been proven to have good outcomes and high response rates in patients with advanced HER2 positive oesophageal cancer. The DECIPHER study will evaluate whether it can have similar outcomes for patients with earlier stage disease that is still treatable with surgery and prevent the cancer returning.

Daniel Griffiths is the Trial Manager for DECIPHER at the Southampton Clinical Trials Unit, and says:

“We will recruit 25 patients who are ctDNA and HER2 positive after their initial chemotherapy and surgery and they will be treated with the targeted cancer drug. The aim of this small study is to see whether this treatment can reduce the amount of ctDNA we see in their blood and assess the safety and side effects of the treatment in this patient group.”

The DECIPHER study is now recruiting patients at Cambridge University Hospitals NHS Foundation Trust, with other hospital sites due to open the trial in the coming months.

Dr Smyth concludes: “This is a good first step to improving outcomes for patients with a high risk, hard to treat cancer after their initial surgery.”

The study is funded by Astra Zeneca and sponsored by the University of Southampton.