Treating Ireland to early phase trials

IRELAND NEEDS to increase its early phase clinical trials activity so that patients have a greater chance to access innovative treatments, according to a leading consultant haematologist, Frank Giles, who is involved in setting up a number of phase one cancer clinical trials here.

Patients on these early trials are among the first to receive treatment regimes that are being assessed, sometimes after years of lab-based or pre-clinical work.

Phase one trials usually involve small numbers of participants to see how well a treatment is tolerated and then, depending on the results, larger phase two and three trials go on to examine the treatment in greater numbers of patients and compare it to the standard approach.

The landscape of early trials is changing dramatically for cancer treatments thanks to technology that can profile a person’s disease at a molecular level, explains Giles, who is professor of cancer therapeutics at NUI Galway and Trinity College Dublin.

“Until recently all the patients on a phase one cancer trial might have had in common is that they had advanced cancer and other treatments hadn’t worked,” he says.

“But now, long before the first person gets the treatment, you have a profile of the people in whom is it likely to be of some value. We try to enrich for or even confine the enrolment to people who have diseases driven by molecular targets at which the novel approach is directed, and so we are increasing the chances that the approach will benefit the patient.”

Over the past couple of decades, Ireland has been building a reputation as a centre for larger, phase three trials for cancer treatments, but we are now increasing our involvement in the earlier phase studies as well, according to Giles.

He and colleagues around the State are currently involved in a trial looking at two oral medications for patients with a type of bone marrow cancer called myelofibrosis.

“One of the drugs was not available in Ireland until this trial, and we knew from preclinical work that the combination of both these drugs is potentially very powerful,” he says.

“Rather than waiting for years for the sequential approval of investigating each of these drugs separately, this trial gave us the chance to bring the combined treatment to patients.”

The phase one study sees Galway University and St James’s Hospitals working alongside centres in France, Italy and Britain.

Competition to get places on the trial has been stiff – slots book up quickly – but five patients in Ireland have been recruited since it opened in January, and Giles reports that the study is progressing well.

“We are very happy with how the patients are doing, and we are presenting the data at an international meeting soon,” he says.

“We are still in the dose-finding part of this study where caution is the priority – we enrol a few patients at a time, watch for any signs of ill effects or disease response, then repeat until we feel we have safe doses. We then can enrol more patients simultaneously to check that our perceptions of safety and anti-cancer activity are accurate.”

One way to improve the odds of patients in Ireland getting places on phase one trials is to build up a broad spectrum of studies, says Giles, and he says there are plans for more early trials to open here soon for patients with other blood and solid tumour cancers.

More generally, the scope of treatments is being broadened, he notes.

“The majority of what we will be offering patients for the foreseeable future are increasingly targeted drugs,” he says. “Future phase one studies will increasingly involve medical devices, viruses, stem cells, vaccines and modified cells.”

However, he cautions that we need to build up the infrastructure in Ireland to support trials for cancer and other disease areas.

He is involved in developing a National Clinical Research Framework, where one of the aims is for existing Health Research Board Clinical Research Facilities around the State to collaborate on trials.

“You need to enable countrywide access in a very competitive global environment,” he says. “That requires an administrative efficiency and nimbleness, optimal organisation of biobanking, contracts, ethics approval, data-management, staff credentialling and training and all the relevant specialised people in place. You also need to be able to disseminate information to medical staff and patients about what trials are running in Ireland.”

The annual meeting of the European Clinical Research Infrastructure Network (ECRIN) takes place on Thursday at the Coach House, Dublin Castle. It will be followed on Friday by a celebration of International Clinical Trials Day, also in Dublin Castle. See molecularmedicineireland.iefor more details