The COOLS trial is a multicenter, phase III randomized controlled trial comparing 2 surgery approaches, one guided with a optical device (VELscope; experimental arm) and one without (control arm), which is different from the conventional drug trial. This is a large scale pan Canadian study to validate an FDA- and Health Canada-approved optical device to better define the surgical margin. We acknowledge the support and the shared vision from the Terry Fox Research Institute.
The uniqueness of this trial is multi-fold. Firstly, this is the first-ever pan Canadian surgical study of such calibre, involving 9 institutions across 6 provinces, more than 70 health professionals, and 400 patients. The 9 institutions are drawn from academic centres with a residency program and affiliated to provincial cancer agencies, with patient populations of interest, linkages to the dental system (referral pathway for patients), and onsite pathology services. The catchment areas of these participating sites cover over the locations from which 70% of oral cancer patients come from. Every year, there are ~3,400 patients diagnosed with oral cancer in Canada and ~60% are early stage oral cancer, which are the target population of our trial. Hence, if the results are validated, it can make enormous impact at the patient level in increasing patients' survival, morbidity, and quality of life, at the institutional level in changing the standard of care, and at the population level in improving the cure rate and reducing costs to the health system.
Secondly, this is an exceptional example of translational research from bench to bedside, from discovery to clinical implication. With the strong support of the ongoing Oral Cancer Predictive Longitudinal (OCPL) Study, BC researchers have built a strong foundation to lead this prospective, multicenter study. The OCPL study is an NIH/NIDCR-funded study which involves ~900 patients with oral precancer and oral cancer that have been monitored regularly since 1999 for progression/recurrence of disease. The OCPL study has served as a pipeline for referral of such patients to the trial in BC .
Thirdly, in order to change clinical practice we need to ascertain clinical efficacy through assessment of local recurrence at the clinical, histological and molecular level, assess the impact on quality of life and cost effectiveness, and construct a plan for KT. The molecular goal will examine the margin to see if the tool can produces a shift in surgical field, sparing normal tissue while catching high-risk occult tissue. The health economics goal will collect relative cost-effective evidence of the two treatments in both the cost per avoided recurrence and the cost per quality-adjusted life years gained and last but not the least, in the knowledge translation (KT) goal, we plan to develop a KT strategy that will facilitate rapid scale up of FV-guided surgery in Canada and beyond. With such a comprehensive package, the COOLS trial promises to collect evidence and information necessary for bridging the gap from discovery to clinical application of FV-guided surgery into an oral cancer solution for patients worldwide.
The COOLS trial is a large-scale study - large number of patients, types of health professional specialties, and geographically widespread institutions. The site establishment, personal training to standardize the protocol including the use of study device, and quality assurance are critical components to the success of the trial. To ensure the quality of the trial, a multidisciplinary trial coordinating centre has been developed to monitor the trial operation and a web-based database application has been created to facilitate the data, images, and sample flow. A data safety monitoring board and a steering committee have been formed to oversee the trial. Additionally, a central pathology review committee (chaired by KWB) has been formed to document and review all the margin pathology of the surgical samples and the adjudication of the endpoint based on the pathology of the follow-up biopsy.
At the time of writing, September 2011, 69 patients have been enrolled from 4 sites. It is anticipated that recruitment will be completed in August, 2013. Follow-up will be completed two years later with results available by 2015.
This trial represents a pan-Canadian partnership of sites and investigators/surgeons and is the first randomized trial of the pan-Canadian Network for Oral Cancer Control or PanCanNOC. The network, serving as the machinery for future research idea/projects, is committed to rigorously evaluating interventions in the prevention and treatment of oral cancer.
Publication and reporting date
Expect late 2015 or early 2016.