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

Phase 2

Recruiting

• Conditions: Oropharyngeal Squamous Cell Carcinoma; Head and Neck Cancer
• Interventions: Procedure: Trans-Oral Surgery (TOS) + Neck Dissection; Radiation: Radiation

• Registration Number: NCT04220749
• Lead Sponsor: Lawson Health Research Institute

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:

1. 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.

2. 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.

3. 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.

Study Timeline

• Study First Submitted: 2020-01-06
• Study First Submitted QC: 2020-01-06
• Study First Posted: 2020-01-07
• Study Start: 2020-06-25
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-02
• Last Update Posted: 2020-09-04
• Primary Completion: 2028-02
• Study Completion: 2028-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 68

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 2, TOS + Neck Dissection	Trans-Oral Surgery (TOS) + Neck Dissection	Trans-oral Surgery (TOS) + Neck Dissection (plus radiation is required)
Arm 1, Radiation +/- Chemotherapy	Radiation	Standard Treatment (Radiation +/- Chemotherapy)

Primary Outcome Measures

Name	Time	Method
Disease-Specific Survival	5 years	Time from randomization to death from cancer

Secondary Outcome Measures

Name	Time	Method
Feeding tube rate at 1 year	Baseline to 1 year post treatment	Measure other functional measurements such as feeding tube rate at 1 year
Progression-Free Survival	5 years	Defined as time from randomization to death from any cause
Distant Failure	5 years	Defined as time from randomization to first distant failure or metastasis (analyzed as cumulative incidence function with death as competing event)
CTCAE Dysphagia Grade	Baseline to 5 years post treatment	Measure other functional measurements such as CTCAE Dysphagia grade
Local-Regional Failure	5 years	Defined as time from randomization to first local-regional failure (analyzed as cumulative incidence function with death as competing event)
Quality of Life	Baseline to 5 years follow up	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	Randomization until 5 years follow up	To determine toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4
Overall Survival	5 years	Time from randomization to death from any cause
Any Failure	5 years	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)

Trial Locations

Locations (1)

London Regional Cancer Program; 🇨🇦 London, Ontario, Canada