Efficacy of Optically-guided Surgery in the Management of Early-staged Oral Cancer - COOLS TRIAL

Summary

Oral squamous cell carcinoma (SCC) is a global disease responsible for \~300,000 new cancer cases each year. Local recurrence (\~30% of cases) and formation of second primary malignancy are common.2, 3 Cosmetic and/or functional compromise associated with treatment of disease stage is often significant. These statistics underscore the urgent need to develop a better approach in order to control this deadly disease.

It is becoming increasingly apparent that oral cancers develop within wide fields of diseased tissue characterized by genetically altered cells that are widespread across the oral cavity and present in clinically and histologically normal oral mucosa. Complete removal of these lesions is difficult because high-risk changes frequently go beyond clinically visible tumor. In recognition of this, current 'best practice' is to remove SCC with a significant width (usually 10 mm) of surrounding normal-looking oral mucosa. However, since occult disease varies in size such approach often results in over-cutting (causing severe cosmetic and functional morbidity) or under removal of disease tissue, as evidenced by frequent positive surgical margins and high local and regional recurrence - a failure of the 'best practice.

There is a wealth of literature that supports the use of tissue autofluorescence in the screening and diagnosis of precancers in the lung, uterine cervix, skin and oral cavity. This approach is already in clinical use in the lung and the mechanism of action of tissue autofluorescence has been well described in the cervix. Changes in fluorescence reflect a complex interplay of alterations to fluorophores in the tissue and structural changes in tissue morphology, each associated with progression of the disease.

As one of the internationally leading teams in applying tissue fluorescence technology, we have shown that direct fluorescence visualization (FV) tools can identify clinically visible or occult premalignant and malignant lesions that are associated with lesions at risk, with high-grade histology and high-risk molecular change. In a recently small scaled, retrospective study, we have shown that FV helped surgeons in the operating room to determine the extent of the high-risk FV field surrounding the cancer and resulted in remarkably lower 2-year recurrence rates (0% for FV-guided vs. 25% for those without FV-guided approach). There is need to design a larger scale prospective, randomized controlled (Phase III) trial to gather strong evidence in proving the efficacy of the surgery approach using this adjunct tool.

To establish the evidence supporting the change in clinical practice using FV-guided surgery. There are 3 objectives.

2.1. Objective 1 (Clinical evidence): To assess the effect of FV-guided surgery on the recurrence-free survival of histologically confirmed disease within the context of a randomized controlled trial (efficacy). Hypothesis: FV-guided surgery will increase the recurrence-free survival.

2.2. Objective 2 (Quality of Life evidence): To establish the cost per recurrence prevented for this approach and assess quality of life issues. Hypothesis: FV-guided surgery can be delivered in a cost effective manner and improve the quality of life of patients 2.3 Objective 3 (Scientific/Molecular evidence): To assess the presence of previously validated molecular markers (microsatellite analysis, LOH) and histological change (quantitative pathology) in surgical margins in a nested case-control study involving a tumor bank created within this project. Hypothesis: FV-guided surgery will spare normal tissue at the same time improving capture of high-risk tissue.

Conditions

• Oral Cancer
• High-grade Precancer

Interventions

PROCEDURE

Fluorescence visualization device

The trial will randomize 200 patients - 100 in the control arm (using conventional white light approach).

PROCEDURE

Fluorescence visualization device

The trial will randomize 200 patients - 100 in the FV arm (using FV guided the surgery margin)

Sponsors & Collaborators

• Terry Fox Research Institute

  collaborator OTHER

• British Columbia Cancer Agency

  collaborator OTHER

• University of British Columbia

  lead OTHER

Principal Investigators

• Catherine Poh, DDS, PhD · University of British Columbia

• Scott Durham, Dr. · University of British Columbia

• Miriam Rosen, Ph.D · Simon Fraser University

• Calum MacAulay, Ph.D · BC Cancer Agency Research Centre

• Penelope Brasher, Ph.D · University of British Columbia

• Stuart Peacock, Ph.D · BC Cancer Agency Research Centre

• Kitty Corbett, Ph.D · Simon Fraser University

• Kenneth Berean, Dr. · University of British Columbia

• Donald Anderson, Dr. · University of British Columbia

• Michele Williams, DDS · British Columbia Cancer Agency

• Joseph Dort, Dr. · University of Calgary

• Robert Hart, Dr. · Dalhousie University

• Mike Odell, Dr. · University of Ontario

• Paul Kerr, Dr. · University of Manitoba

• John Yoo, Dr. · Western University, Canada

• Kevin Higgins, Dr. · Sunnybrook Hospital

• Karen Kost, Dr. · McGill University Health Centre/Research Institute of the McGill University Health Centre

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

19 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-01-31

Primary Completion

2014-12-31

Completion

2015-06-30

Countries

• Canada

Study Locations