Interventional oncologists begin running US National Cancer Institute cooperative group trial

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Michael C Soulen

An important opportunity has opened up for interventional oncologists as WCIO leaders take the helm of the E1208 trial. Michael C Soulen writes that the change in the trial leadership from medical oncology to interventional oncology represents a challenge because it rests on the question: can interventional oncologists run a successful cooperative group trial of image-guided therapy? 

E1208 is a phase III randomised, double-blind trial of chemoembolization with or without sorafenib in unresectable hepatocellular carcinoma (HCC) in patients with and without vascular invasion. This article was first published in the IO Insights monthly e-newsletter from IO central.

 

By Michael C Soulen

National Cancer Institute (NCI) cooperative group trials of interventional oncology therapies are few and far between, with a dismal track record; so much so that interventional radiologists have the reputation in the NCI community of being ”unable to do trials”.


Unfortunately we still lack a clinical trials group for interventional oncology, so to access the resources needed for national multicentre trials requires either industry funding—a rare thing on this scale from the device world—or the national cooperative groups. The NCI (known among cynics as the “National Chemotherapy Institute”) cooperative groups are run by medical oncologists with pervasive influence from Big Pharma, who have little interest in interventional oncology studies. Even the radiology cooperative group, ACRIN, was largely unsuccessful in completing the few interventional oncology trials it attempted. (Disclosure: I was the principal investigator of one of the failed trials, though it was six years before I gave up.)

There are some breaths of fresh air from our industry colleagues. Merit Medical, BTG and Sirtex are all running multicentre embolotherapy trials for hepatocellular carcinoma (HCC) and/or liver metastases.

E1208 was activated in October 2009. The primary endpoint is progression-free survival, with a planned accrual of 200 patients in each arm. Jeff Geschwind and I served as the interventional radiology co-chairs for the protocol design, but the trial has been run largely by medical oncologists. Among the 123 sites approved to accrue to the study, only one has a recognized interventional radiologist as the site. Accrual has been a dismal 167 patients over the past four years, less than half of the planned rate. Only three centres in the country have enrolled 10 or more patients. There have been a number of bumps in the road: the interruption in Lipiodol supply in 2010, cessation of production of powdered cisplatin in 2010, and ongoing shortages of powdered doxorubicin all required trial interruption and revision to allow use of drug-eluting beads. Nonetheless, accrual has remained so poor that the Eastern Cooperative Oncology Group (ECOG) Data and Safety Monitoring Board and the medical oncologists on the steering committee recommended consideration of closing the trial.

In a recent turn of events, the medical oncology principal investigator for E1208 left, and the leadership turned to Peter O’Dwyer, a Penn medical oncologist and interventional oncology enthusiast. Dr. O’Dwyer saw the futility in medical oncologists running an interventional oncology trial, and asked us to take it over. In essence, he has thrown down the gauntlet: can interventional oncologists run a successful cooperative group trial of image-guided therapy? This is an historic opportunity; for the first time, interventionalists are running an NCI cooperative group trial. Jeff Geschwind (professor of Radiology, Surgery and Oncology, Johns Hopkins University School of Medicine and director, Vascular and Interventional Radiology, Baltimore, USA) will take over as the principal investigator, with Riad Salem (Medical director of Interventional Oncology, Northwestern Memorial Hospital and professor of Radiology at Northwestern University, Illinois, USA) and myself as the co-chairs.

Call to action 

As an interventional oncology community, we need to rise to this challenge. We do not want to be left holding the blame for the failure of the study. Trials of interventional oncology therapies are difficult to accrue. Having treatment arms involving different specialists, instead of the patient being managed by a single doctor, is a major negative accrual factor for any trial. Interventional oncologists doing chemoembolization should be able to prescribe and manage sorafenib; but if you are not comfortable, then team up with a medical oncologist or hepatologist from your HCC team who is. Coordinator support from the cooperative groups is very sparse; your cancer centre should supply a coordinator funded by your group. It is an intergroup trial. Make sure the trial is active at your site, and that your HCC tumour board funnels eligible patients to the trial. See http://ecog.dfci.harvard.edu/general/E1208info.html for physician and patient information about the trial.

Jeff, Riad and I will be reaching out to centres likely to be able to put patients on the study. We need the concerted effort of the interventional oncology community to prove to our medical oncology, surgical oncology, and radiation oncology colleagues that we can do trials too, and cement our credibility as the fourth pillar of cancer care. 

Michael C Soulen is professor of Radiology and Surgery at Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA and WCIO past chair.