DECIPHER Trial for patients with gastro-oesophageal adenocarcinoma, tests whether a targeted cancer drug can help patients with a hard-to-treat cancer. A single-arm phase II trial of trastuzumab deruxtecan in patients with gastro-oesophageal adenocarcinoma cancer who are ctDNA and HER2 positive.

Background:

Gastro-oesophageal adenocarcinoma is a cancer found at the junction of the stomach and the oesophagus (food-pipe) and is often diagnosed late, making it difficult to treat effectively and with a higher chance of the cancer returning (recurrence).

The current standard treatment is FLOT chemotherapy, surgery, and then another round of FLOT. However, even patients who complete this often experience recurrence, particularly if they have circulating tumour DNA (ctDNA) in their blood post-surgery. ctDNA refers to small fragments of genetic material from the tumour found in the blood.

Aim:

This trial aims to evaluate the safety and effectiveness of trastuzumab deruxtecan (T-DXd) in treating patients with HER2-positive tumors who have circulating tumor DNA (ctDNA) after surgery. HER2 positive indicates an over-expression of the protein HER2 on the surface of tumor cells. T-DXd consists of the chemotherapy drug deruxtecan and antibody trastuzumab, which binds to HER2, allowing it to be taken into the cells where it can then kill the cell from within.

Method:

HER2-positive, ctDNA-positive patients will be recruited to receive T-DXd to assess if it reduces ctDNA levels and improves survival chances. Treatment is in 21-day cycles, with T-DXd administered on day one, for up to 8 cycles.

Treatment stops if the patient completes 8 cycles, experiences cancer recurrence, severe side effects, leaves the study, or dies.

Objective:

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, the effect on quality of life and increase the period of cancer-free survival, or preventor prevent the cancer returning.

This trial is currently recruiting the UK.

If successful, this trial could offer a new treatment option to help prevent recurrence in patients with HER2-positive gastro-oesophageal cancer who remain at high risk after standard therapy.

Glossary:

HER2, the human epidermal growth factor receptor 2 gene, can be detected in circulating tumor DNA (ctDNA), meaning that the presence of HER2 amplification in ctDNA can indicate the existence of HER2-positive cancer, even when a tissue biopsy is not available; this allows for monitoring of treatment response and disease progression through liquid biopsy analysis of ctDNA. 

Circulating tumor DNA (ctDNA) is DNA that comes from cancer cells and is found in a person’s blood. It’s a biomarker that can help diagnose cancer, plan treatment, and monitor cancer’s progress. 

FLOT: Fluorouracil, oxaliplatin and docetaxel are chemotherapy drugs. These chemotherapy drugs destroy quickly dividing cells, such as cancer cells. Leucovorin is a drug that helps fluorouracil to work better.

The Trial is being run at the CRUK Southampton Clinical Trials Unit with Researchers at the University of Oxford.

The trial is recruiting patients at Cambridge University Hospital NHS Foundation Trust with 11 other sites open and starting to recruit.

Dave Chuter and Ceri Steele are PPI members of the Trial management Group and have been involved in all discussions from the design stage.

Learn more about HER2 Testing and Treatment: Gastric Cancer HER2 Testing Infographic – Digestive Cancers Europe

Authors:

Dave Chuter

Ceri Steele