A clinical trial designed and co-ordinated by the University of Birmingham’s Cancer Research UK Clinical Trials Unit to test an experimental drug in patients with head and neck cancer has launched today through the Combinations Alliance, a joint initiative between Cancer Research UK and the Experimental Cancer Medicine Centres (ECMC) Network.

The University of Birmingham reports the trial, called WISTERIA, is the first Combinations Alliance clinical trial to be sponsored by the University of Birmingham and will be conducted at Queen Elizabeth Hospital, Birmingham, Clatterbridge Cancer Centre, Wirral, University College London, the Institute of Cancer Research, London, and Beatson West of Scotland Cancer Centre, Glasgow.

Researchers want to find out whether using Astra Zeneca’s AZD1775 experimental compound, in combination with chemotherapy before surgery or with chemotherapy and radiotherapy after surgery, is more effective and reduces the risk of the cancer returning. They also want to find out if the combination of AZD1775 and chemotherapy before surgery decreases the need for further treatment after surgery.

The phase I trial will determine whether it is safe to combine AZD1775 with pre-surgery cisplatin chemotherapy and post-surgery cisplatin chemotherapy and radiotherapy in patients with head and neck cancer, and what dose is best. AZD1775 acts as a potent inhibitor of WEE1, a protein which regulates the cell cycle, and it has been shown to increase the effectiveness of both cisplatin chemotherapy and radiotherapy in pre-clinical studies. It is one of AstraZeneca’s portfolio of DNA Damage Response compounds.

There will be two groups of up to twenty one patients taking part in the trial co-ordinated by the Cancer Research UK Clinical Trials Unit at the University of Birmingham. The first group will receive AZD1775 with chemotherapy before surgery and the second will receive AZD1775 in addition to chemotherapy and radiotherapy after surgery. Standard treatment for high risk head and neck cancer is surgery followed by cisplatin chemotherapy and radiotherapy. While this treatment is the most effective option for patients, survival is still poor and the treatment often has a significant impact on quality of life for survivors.

Professor Hisham Mehanna, of the Institute of Cancer and Genomic Studies at the University of Birmingham, said “Many patients diagnosed with aggressive types of head and neck cancer are at a high risk of relapse after surgery, so we urgently need to find new ways to treat the disease and reduce the risk of it returning. We hope that combining this drug with chemotherapy will mean that treatment is more effective helping more people survive, and that those cured will have a better quality of life after treatment.”

Anthony Johnson, VP Early Clinical Development, Innovative Medicines and Early Development Biotech Unit at AstraZeneca, said “We are excited about this new clinical trial evaluating AZD1775 in combination with chemotherapy and radiation in head and neck cancer patients. There is a strong scientific rationale for running this trial and we hope that this will bring clinical benefit to patients.”

Researchers on this window of opportunity trial are accepting treatment naïve patients aged between eighteen and seventy with cancer of the mouth, throat and voice box and are due to undergo surgery.

Dr Ian Walker, Cancer Research UK’s director of clinical research, said “We’re excited to have the opportunity to trial this new drug through our Combinations Alliance initiative. The initiative allows us to bring together combinations of treatments, using drugs that are in development, that wouldn’t otherwise be possible. And we look forward to seeing if this drug can improve treatment options for patients with head and neck cancer.”