SPIRE trial Spotlight

Q.     Describe the trial and the anticipated patient benefit.

This Southampton ECMC trial will combine a novel DNA methyltransferase inhibitor, SGI-110, with cisplatin and gemcitabine chemotherapy. This is based on pre-clinical data showing that hypomethylating agents can reverse cisplatin resistance mechanisms in a variety of solid malignancies, including bladder cancer. The trial has an initial dose escalation phase in advanced solid malignancies followed by a randomised expansion phase as neoadjuvant therapy for bladder cancer. We have incorporated PD endpoints looking at global DNA methylation. We hope to develop this as a means to improve on the standard systemic therapy for this disease which has not changed in over a decade.

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

We had actually tried previously by approaching other potential pharma partners directly but we had been unable to get them to engage. This opportunity through the ECMC Combinations Alliance allowed us to interact directly with a company that was receptive to a trial of this nature. Interestingly our collaborators from the Sheffield ECMC, Sarah Danson and Jim Catto, had proposed a virtually identical design. This allowed us to combine forces and drive the concept forward as a team which has been very helpful and productive.

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

The Alliance is great in bringing together a clinical academic team with an exciting idea and the key people within a pharma partner. Facilitating this aspect of the process by the ECMC Combinations Alliance team is extremely important in getting ideas moving forward and fostering the development of a concept - the concept for the SPIRE trial may not have happened otherwise.

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

Trial implementation time lines are always a frustrating issue. Some of this is simply out of your control as an investigator in terms of the rules of the regulatory process. However for our next trial we are working to try to shorten the time from concept acceptance by the Alliance and pharma partner and getting to a working protocol as this aspect is within our control.

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

Start with a strong scientific rationale (of course) and engage enthusiastic collaborators at an early stage.