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Radiotherapy vs. Trans-Oral Surgery for HPV-Negative Oropharyngeal Squamous Cell Carcinoma

Primary Purpose

Head and Neck Cancer, Oropharyngeal Squamous Cell Carcinoma

Status

Recruiting

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Radiation

Trans-Oral Surgery (TOS) + Neck Dissection

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring Radiotherapy, Trans-Oral Surgery, HPV-Negative, Randomized

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age 18 years or older
Willing to provide informed consent
ECOG performance status 0-2
Histologically confirmed squamous cell carcinoma
HPV-negative tumor, as determined by: negative p16 status, real time PCR or in-situ hybridization. Central confirmation is not required prior to randomization. Equivocal/uncertain HPV status will be allowed on trial.
Primary tumor site in the oropharynx (includes tonsil, soft palate, base of tongue, walls of oropharynx)
Tumor stage: T1 or T2, with likely negative resection margins at surgery
Nodal stage: N0-3. Patients with positive nodal disease and extranodal extension on imaging may be included at the surgeon's discretion, if the nodal disease is deemed resectable by the operating surgeon.
Eligible for curative intent treatment, with likely negative resection margins at surgery. For patients where adequate transoral access is in question, they will first undergo an examination under anesthesia prior to randomization to ensure adequate exposure can be obtained.
Blood work obtained within 4 weeks prior to randomization, with adequate bone marrow function, hepatic, and renal function, as determined by the investigator.
Patient assessed by a radiation oncologist and surgeon and presented at multidisciplinary tumor board prior to randomization. If not feasible, case can be discussed with study Principal Investigator.

Exclusion Criteria:

Serious medical comorbidities or other contraindications to radiotherapy, chemotherapy or surgery
Prior history of head and neck cancer within 5 years
Prior head and neck radiation at any time
Metastatic disease
Inability to attend full course of radiotherapy or follow-up visits
Prior invasive malignant disease unless disease-free for at least 5 years or more, with the exception of non-melanoma skin cancer
Unable or unwilling to complete QOL questionnaires
Pregnant or lactating women

Sites / Locations

London Regional Cancer ProgramRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm 1, Radiation +/- Chemotherapy

Arm 2, TOS + Neck Dissection

Arm Description

Standard Treatment (Radiation +/- Chemotherapy)

Trans-oral Surgery (TOS) + Neck Dissection (plus radiation is required)

Outcomes

Primary Outcome Measures

Disease-Specific Survival

Time from randomization to death from cancer

Secondary Outcome Measures

Overall Survival

Time from randomization to death from any cause

Progression-Free Survival

Defined as time from randomization to death from any cause

Local-Regional Failure

Defined as time from randomization to first local-regional failure (analyzed as cumulative incidence function with death as competing event)

Distant Failure

Defined as time from randomization to first distant failure or metastasis (analyzed as cumulative incidence function with death as competing event)

Any Failure

Defined as time from randomization to first local-regional failure or distant failure, whichever occurs first (analyzed as cumulative incidence function with death as competing event)

Quality of Life

Quality of Life using the following questionnaire: MD Anderson Dysphagia Inventory (MDADI)

Quality of Life

Quality of Life using the following questionnaire: EORTC QLQ-C30

Quality of Life

Quality of Life using the following questionnaire: H&N35 scale

Quality of Life

Quality of Life using the following questionnaire: Voice Handicap Index (VHI-10)

Quality of Life

Quality of Life using the following questionnaire: Neck Dissection Impairment Index (NDII)

Quality of Life

Quality of Life using the following questionnaire: Patient Neurotoxicity Questionnaire (PNQ)

Toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4

To determine toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4

Feeding tube rate at 1 year

Measure other functional measurements such as feeding tube rate at 1 year

CTCAE Dysphagia Grade

Measure other functional measurements such as CTCAE Dysphagia grade

Full Information

NCT ID

NCT04220749

First Posted

January 6, 2020

Last Updated

September 2, 2020

Sponsor

Lawson Health Research Institute

1. Study Identification

Unique Protocol Identification Number

NCT04220749

Brief Title

Radiotherapy vs. Trans-Oral Surgery for HPV-Negative Oropharyngeal Squamous Cell Carcinoma

Official Title

A Phase II Randomized Trial for HPV-Negative Oropharyngeal Squamous Cell Carcinoma: Radiotherapy vs. Trans-Oral Surgery (ORATOR)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2020

Overall Recruitment Status

Recruiting

Study Start Date

June 25, 2020 (Actual)

Primary Completion Date

February 2028 (Anticipated)

Study Completion Date

February 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Lawson Health Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The goal of this randomized phase II study is a formal comparison of radiotherapy versus trans-oral surgery as the primary treatment of HPV-negative patients with early-stage oropharyngeal carcinoma.

Detailed Description

This study is designed as a randomized phase II study. Patients will be randomized between current standard of care treatment (Arm 1) vs. TOS (Arm 2) in a 1:1 ratio. Additionally, patients will be stratified according to T stage (T1 vs. T2); N stage (N0/1 vs. N2/3) The randomized phase II design is required for three reasons: The randomization will provide an appropriate control group to serve as a comparator for the experimental arm. Historical or contemporaneous non-randomized controls would not be appropriate due to the multitude of biases that could be introduced by patient selection and other confounders. A small sample size will allow for adequate power to assess for progression-free survival, and also an assessment of quality of life, overall survival and toxicity. The results will allow for a decision as to whether a multi-institutional phase III trial is warranted, and inform the design of such a trial.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Head and Neck Cancer, Oropharyngeal Squamous Cell Carcinoma

Keywords

Radiotherapy, Trans-Oral Surgery, HPV-Negative, Randomized

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

2 Arm study randomized in a 1:1 ratio

Masking

None (Open Label)

Allocation

Randomized

Enrollment

68 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm 1, Radiation +/- Chemotherapy

Arm Type

Active Comparator

Arm Description

Standard Treatment (Radiation +/- Chemotherapy)

Arm Title

Arm 2, TOS + Neck Dissection

Arm Type

Experimental

Arm Description

Trans-oral Surgery (TOS) + Neck Dissection (plus radiation is required)

Intervention Type

Radiation

Intervention Name(s)

Radiation

Other Intervention Name(s)

Chemotherapy, if required

Intervention Description

Standard of Care: Radiation +/- Chemotherapy

Intervention Type

Procedure

Intervention Name(s)

Trans-Oral Surgery (TOS) + Neck Dissection

Other Intervention Name(s)

Radiation, if required

Intervention Description

Trans-Oral Surgery (TOS) + Neck Dissection (plus radiation, if required)

Primary Outcome Measure Information:

Title

Disease-Specific Survival

Description

Time from randomization to death from cancer

Time Frame

5 years

Secondary Outcome Measure Information:

Title

Overall Survival

Description

Time from randomization to death from any cause

Time Frame

5 years

Title

Progression-Free Survival

Description

Defined as time from randomization to death from any cause

Time Frame

5 years

Title

Local-Regional Failure

Description

Defined as time from randomization to first local-regional failure (analyzed as cumulative incidence function with death as competing event)

Time Frame

5 years

Title

Distant Failure

Description

Defined as time from randomization to first distant failure or metastasis (analyzed as cumulative incidence function with death as competing event)

Time Frame

5 years

Title

Any Failure

Description

Defined as time from randomization to first local-regional failure or distant failure, whichever occurs first (analyzed as cumulative incidence function with death as competing event)

Time Frame

5 years

Title

Quality of Life

Description

Quality of Life using the following questionnaire: MD Anderson Dysphagia Inventory (MDADI)

Time Frame

Baseline to 5 years follow up

Title

Quality of Life

Description

Quality of Life using the following questionnaire: EORTC QLQ-C30

Time Frame

Baseline to 5 years follow up

Title

Quality of Life

Description

Quality of Life using the following questionnaire: H&N35 scale

Time Frame

Baseline to 5 years follow up

Title

Quality of Life

Description

Quality of Life using the following questionnaire: Voice Handicap Index (VHI-10)

Time Frame

Baseline to 5 years follow up

Title

Quality of Life

Description

Quality of Life using the following questionnaire: Neck Dissection Impairment Index (NDII)

Time Frame

Baseline to 5 years follow up

Title

Quality of Life

Description

Quality of Life using the following questionnaire: Patient Neurotoxicity Questionnaire (PNQ)

Time Frame

Baseline to 5 years follow up

Title

Toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4

Description

To determine toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4

Time Frame

Randomization until 5 years follow up

Title

Feeding tube rate at 1 year

Description

Measure other functional measurements such as feeding tube rate at 1 year

Time Frame

Baseline to 1 year post treatment

Title

CTCAE Dysphagia Grade

Description

Measure other functional measurements such as CTCAE Dysphagia grade

Time Frame

Baseline to 5 years post treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 18 years or older Willing to provide informed consent ECOG performance status 0-2 Histologically confirmed squamous cell carcinoma HPV-negative tumor, as determined by: negative p16 status, real time PCR or in-situ hybridization. Central confirmation is not required prior to randomization. Equivocal/uncertain HPV status will be allowed on trial. Primary tumor site in the oropharynx (includes tonsil, soft palate, base of tongue, walls of oropharynx) Tumor stage: T1 or T2, with likely negative resection margins at surgery Nodal stage: N0-3. Patients with positive nodal disease and extranodal extension on imaging may be included at the surgeon's discretion, if the nodal disease is deemed resectable by the operating surgeon. Eligible for curative intent treatment, with likely negative resection margins at surgery. For patients where adequate transoral access is in question, they will first undergo an examination under anesthesia prior to randomization to ensure adequate exposure can be obtained. Blood work obtained within 4 weeks prior to randomization, with adequate bone marrow function, hepatic, and renal function, as determined by the investigator. Patient assessed by a radiation oncologist and surgeon and presented at multidisciplinary tumor board prior to randomization. If not feasible, case can be discussed with study Principal Investigator. Exclusion Criteria: Serious medical comorbidities or other contraindications to radiotherapy, chemotherapy or surgery Prior history of head and neck cancer within 5 years Prior head and neck radiation at any time Metastatic disease Inability to attend full course of radiotherapy or follow-up visits Prior invasive malignant disease unless disease-free for at least 5 years or more, with the exception of non-melanoma skin cancer Unable or unwilling to complete QOL questionnaires Pregnant or lactating women

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Susan Archer

Phone

519-685-8618

susan.archer@lhsc.on.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Danielle MacNeil, M.D.

Organizational Affiliation

London Regional Cancer Program, London Health Sciences Centre

Official's Role

Principal Investigator

Facility Information:

Facility Name

London Regional Cancer Program

City

London

State/Province

Ontario

ZIP/Postal Code

N6A 5W9

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Danielle MacNeil, MD

Phone

519-658-8600

Danielle.Macneil@lhsc.on.ca

12. IPD Sharing Statement

Learn more about this trial

Radiotherapy vs. Trans-Oral Surgery for HPV-Negative Oropharyngeal Squamous Cell Carcinoma

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