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

NCT01039298 | Unknown Phase 3 DMC

• 1 other identifier: H09-03090
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 8

Brief 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

Keywords

Oral cancer; fluorescence visualization; surgical margin; recurrence

Outcome Measures

Primary Outcomes (1)

• Recurrence-free survival

  5 years

Secondary Outcomes (1)

• Histological and molecular evidence of positive margins and quality of life

  5 years

Study Arms (2)

A

ACTIVE COMPARATOR

All subjects in this study will receive surgery to treat their oral lesions. The margins (or boundaries) of the tissue to be removed during surgery will be defined by 2 different procedures (or study arms) in the operating room. The Control arm. Surgical boundaries for oral lesions will be defined under regular white light.

Procedure: Fluorescence visualization device

B

EXPERIMENTAL

All subjects in this study will receive surgery to treat their oral lesions. The margins (or boundaries) of the tissue to be removed during surgery will be defined by 2 different procedures (or study arms) in the operating room. The FV arm (experimental arm). Surgical boundaries for oral lesions will be defined by FV.

Procedure: Fluorescence visualization device

Interventions

Fluorescence visualization device PROCEDURE

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

B

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with severe dysplasia, carcinoma in situ, invasive squamous cell carcinoma (T1 or T2) of the oral cavity (ICO-D site codes: C02.0-C06.9) who will be undergoing curative resection (primary disease).

You may not qualify if:

• Patients with a non-oral malignancy diagnosed (not including non-melanoma skin cancer and lymphoma outside of head and neck region) within the past 3 years.
• Patients with evidence of distant metastasis (as determined by CAT and X-ray) at the time of recruitment.

Sponsors & Collaborators

• University of British Columbia: lead
• Terry Fox Research Institute: collaborator
• British Columbia Cancer Agency: collaborator

Study Sites (8)

University of Calgary

Calgary, Alberta, Canada

RECRUITING

BC Cancer Agency (Vancouver & Fraser Valley Centres) & Vancouver General Hospital

Vancouver, British Columbia, Canada

RECRUITING

CancerCare Manitoba, University of Manitoba

Winnipeg, Manitoba, Canada

RECRUITING

Victoria General Hospital, Dalhousie University

Halifax, Nova Scotia, Canada

RECRUITING

London Health Science Centre, University of Western Ontario

London, Ontario, Canada

RECRUITING

Ottawa General Hospital, University of Ontario

Ottawa, Ontario, Canada

RECRUITING

Sunnybrook Hospital

Toronto, Ontario, Canada

RECRUITING

McGill University Health Centre

Montreal, Quebec, Canada

RECRUITING

Related Publications (2)

• Durham JS, Brasher P, Anderson DW, Yoo J, Hart R, Dort JC, Seikaly H, Kerr P, Rosin MP, Poh CF. Effect of Fluorescence Visualization-Guided Surgery on Local Recurrence of Oral Squamous Cell Carcinoma: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2020 Dec 1;146(12):1149-1155. doi: 10.1001/jamaoto.2020.3147.

  PMID: 33034628 DERIVED

• Poh CF, Durham JS, Brasher PM, Anderson DW, Berean KW, MacAulay CE, Lee JJ, Rosin MP. Canadian Optically-guided approach for Oral Lesions Surgical (COOLS) trial: study protocol for a randomized controlled trial. BMC Cancer. 2011 Oct 25;11:462. doi: 10.1186/1471-2407-11-462.

  PMID: 22026481 DERIVED

MeSH Terms

Conditions

Mouth Neoplasms; Margins of Excision; Recurrence

Condition Hierarchy (Ancestors)

Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Morphological and Microscopic Findings; Pathological Conditions, Signs and Symptoms; Disease Attributes; Pathologic Processes

Study Officials

• Catherine Poh, DDS, PhD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

• Scott Durham, Dr.

  University of British Columbia

  PRINCIPAL INVESTIGATOR

• Miriam Rosen, Ph.D

  Simon Fraser University

  PRINCIPAL INVESTIGATOR

• Calum MacAulay, Ph.D

  BC Cancer Agency Research Centre

  STUDY DIRECTOR

• Penelope Brasher, Ph.D

  University of British Columbia

  STUDY DIRECTOR

• Stuart Peacock, Ph.D

  BC Cancer Agency Research Centre

  STUDY DIRECTOR

• Kitty Corbett, Ph.D

  Simon Fraser University

  STUDY DIRECTOR

• Kenneth Berean, Dr.

  University of British Columbia

  STUDY DIRECTOR

• Donald Anderson, Dr.

  University of British Columbia

  STUDY CHAIR

• Michele Williams, DDS

  British Columbia Cancer Agency

  STUDY CHAIR

• Joseph Dort, Dr.

  University of Calgary

  STUDY CHAIR

• Robert Hart, Dr.

  Dalhousie University

  STUDY CHAIR

• Mike Odell, Dr.

  University of Ontario

  STUDY CHAIR

• Paul Kerr, Dr.

  University of Manitoba

  STUDY CHAIR

• John Yoo, Dr.

  Western University, Canada

  STUDY CHAIR

• Kevin Higgins, Dr.

  Sunnybrook Hospital

  STUDY CHAIR

• Karen Kost, Dr.

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  STUDY CHAIR

Central Study Contacts

Helen Chiu

CONTACT

604-675-8057; hchiu@bccancer.bc.ca

Sylvia Lam

CONTACT

604-675-8057; sau@bccancer.bc.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2009
• First Posted: December 24, 2009
• Study Start: January 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: June 1, 2015
• Last Updated: September 10, 2014

Record last verified: 2014-09

Locations

CA (8)