WISTERIA trial Spotlight

Q. Describe the trial and the anticipated patient benefit.

The Birmingham ECMC WISTERIA Trial is a phase I dose-finding trial which will investigate whether it is safe and effective to combine a drug called AZD1775 with pre-surgery cisplatin and post-surgery cisplatin chemotherapy and radiotherapy in treating patients with head and neck cancer. AZD1775 is a drug that acts as a potent inhibitor of WEE1 and it has been shown to increase the effect of other chemotherapy drugs in the pre-clinical setting.

Head and neck cancer is the sixth most common cancer worldwide. Combined treatment of surgery followed by cisplatin chemotherapy and radiotherapy is the standard of care and is recommended to the 50% of patients who have poor prognostic histological features after surgery. But patients with certain histopathological features after surgery are at increased risk of local recurrence and death. Whilst chemo-radiation improves cure rates, three-year overall survival remains sub-optimal at 50-70% and treatment has a significant impact on quality of life for these patients. There is therefore a pressing need to develop novel approaches that reduces the risk of local recurrence for those with a poor prognosis and reduces the need for post-surgery chemo-radiation. Achieving this may translate into improved overall survival and an enhancement in patient-related outcome measures for this patient group.

Q. Would you have considered such a trial if not working through the ECMC Combinations Alliance?

We may have, but we think it would have been a much longer and difficult process.

Q. Has the experience been different working through the CA? What would you say are the key benefits of working through the Alliance?

The biggest benefit of working through the ECMC Combinations Alliance (CA) is that it has given us access to a new agent that may not otherwise have been accessible to us. Without the support of the CA and making access to AZD1775 possibly, we might not have been able to consider this study or investigate this new treatment paradigm.

Going through the Alliance has also been a different way of working for our trials team, as it has felt more like a partnership with the pharmaceutical company. AstraZeneca have been very supportive of us during the design of the trial by providing their input into the trial design and highlighting certain aspects that they would like investigated but still respecting that the study is ultimately ours.

We were also given highly constructive feedback by the NAC committee, which really helped focus the design of the trial and the protocol development from the original application. This helped ensure the trial remained feasible.  

Having the ECMC Combinations Alliance has also helped simplify contract negations with AstraZeneca and other third parties through It has also been very beneficial having the support of the Alliance team in overcoming any issues as well as allowing our trial team to share best practice with other CA studies. The support of the Alliance has also been beneficial to our trials team setting up the study and being able to offer them advice when required.

Q. What have been the particular challenges for the set-up of WISTERIA?

One of the biggest challenges during trial set up has developing the trial protocol to ensure that it continued to meet our initial trial objectives to incorporate AZD1775 in the clinical management of head and neck patients.

It has also been difficult to deal with the emerging toxicity profile of AZD1775 and incorporating new data into the trial design. At various stages during the protocol development, AstraZeneca have provided us with new emerging data regarding the trial drug which has caused us to change direction in the design of the trial.

But despite these challenges, we are determined to ensure the successful delivery of this study and to generate novel data regarding AZD1775 in the treatment of patients with Head and Neck Cancer.

Q. Would you have any advice to others about to undertake a similar role?

One of the key things has been to identify the investigator sites and the local PIs at an early stage of trial set up. Doing this for WISTERIA has allowed us to get advice from the sites regarding certain aspects of the trial protocol to ensure that they were on board with any trial specific guidelines that might be different to local practice.