Smiling image of woman with glasses.

From idea to innovation: Dr Fiona Chionh on the VADER trial

Dr Fiona Chionh is a medical oncologist at Austin Hospital as well as a clinician-scientist at the Olivia Newton-John Cancer Research Institute, with a focus on translational research in gastrointestinal (GI) cancers.

Dr Chionh describes herself as a passionate clinician-scientist who wants to improve the lives of patients with GI cancers. “I am motivated to be involved in GI cancer trials and translational research because of the need to find more effective as well as better tailored treatments,” she said.

Dr Chionh is a Co-Chair for the latest AGITG trial, VADER, working alongside Prof Niall Tebbutt and Prof John Mariadason. VADER comprises a clinical trial and a translational study for RAS wild type metastatic colorectal cancer.

The premise

“In the clinic, we use a class of drugs called EGFR inhibitors to treat some patients with advanced colorectal cancer,” said Dr Chionh.

“While EGFR inhibitors effectively inhibit tumour cell growth, they do not consistently induce apoptosis, or programmed cell death, in colorectal cancer cells.

“Research in our laboratory at Olivia Newton-John Cancer Research Institute (ONJCRI) has shown that when you add a type of drug called a HDAC inhibitor to an EGFR inhibitor, this combination more effectively causes death of cancer cells and suppresses growth of colorectal cancers.”

The idea

The VADER trial is drawing upon an existing drug – to use in a new way.

“Sodium valproate, which has already been used for over 50 years as medication to treat epilepsy and mood disorders, also has activity as a HDAC inhibitor and has been shown to have anti-cancer activity in the laboratory,” said Dr Chionh.

“The Phase II VADER trial will study the effectiveness of combination treatment with EGFR inhibitors and sodium valproate in patients with advanced colorectal cancer.”

The innovation

The idea for VADER was presented to the inaugural AGITG Idea Generation Workshop in 2019. Through the workshop and the AGITG research review process, it was further refined and developed into the design it is today.

“We will recruit a total of 90 patients undergoing first-line treatment for advanced colorectal cancer. Patients will be randomly allocated to receive maintenance treatment with either combination EGFR inhibitor and sodium valproate or EGFR inhibitor alone. We will then compare outcomes in these two groups,” said Dr Chionh.

The VADER trial later received a 2020 AGITG Innovation Grant and, more recently, a grant from the Medical Research Future Fund (MRFF).

Dr Chionh noted that it was these initial community grants that gave the team a chance to be considered for further funding. “We are grateful to all of the generous donors who made the Innovation Grant possible,” she said.

“Importantly, the awarding of the Innovation Grant was leveraged in a successful subsequent application to the MRFF for additional funding for the VADER trial, enabling more patients and sites to be supported.”

She hopes that the trial will lead to effective improvement in treatment for patients with metastatic colorectal cancer.

“This trial is important because it will determine whether there is a positive signal indicating that combination treatment with EGFR inhibitor and sodium valproate is effective in patients with advanced colorectal cancer,” Dr Chionh said.

“If positive, the study will potentially lead to a larger Phase III AGITG-led study which could define a new treatment option for patients with advanced colorectal cancer.”

Learn more about VADER

Genesis of the VADER clinical trial