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

Sponsor

Lawson Health Research Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT04220749

Collaborator

(none)

Enrollment

Location

Arms

91.2

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer Oropharyngeal Squamous Cell Carcinoma	Radiation: Radiation Procedure: Trans-Oral Surgery (TOS) + Neck Dissection	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

68 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

2 Arm study randomized in a 1:1 ratio2 Arm study randomized in a 1:1 ratio

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 25, 2020

Anticipated Primary Completion Date :

Feb 1, 2028

Anticipated Study Completion Date :

Feb 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1, Radiation +/- Chemotherapy Standard Treatment (Radiation +/- Chemotherapy)	Radiation: Radiation Standard of Care: Radiation +/- Chemotherapy Other Names: Chemotherapy, if required
Experimental: Arm 2, TOS + Neck Dissection Trans-oral Surgery (TOS) + Neck Dissection (plus radiation is required)	Procedure: Trans-Oral Surgery (TOS) + Neck Dissection Trans-Oral Surgery (TOS) + Neck Dissection (plus radiation, if required) Other Names: Radiation, if required

Arm

Intervention/Treatment

Active Comparator: Arm 1, Radiation +/- Chemotherapy

Standard Treatment (Radiation +/- Chemotherapy)

Radiation: Radiation

Standard of Care: Radiation +/- Chemotherapy

Other Names:

Chemotherapy, if required

Experimental: Arm 2, TOS + Neck Dissection

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

Procedure: Trans-Oral Surgery (TOS) + Neck Dissection

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

Other Names:

Radiation, if required

Outcome Measures

Primary Outcome Measures

Disease-Specific Survival [5 years]
Time from randomization to death from cancer

Secondary Outcome Measures

Overall Survival [5 years]
Time from randomization to death from any cause
Progression-Free Survival [5 years]
Defined as time from randomization to death from any cause
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)
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)
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)
Quality of Life [Baseline to 5 years follow up]
Quality of Life using the following questionnaire: MD Anderson Dysphagia Inventory (MDADI)
Quality of Life [Baseline to 5 years follow up]
Quality of Life using the following questionnaire: EORTC QLQ-C30
Quality of Life [Baseline to 5 years follow up]
Quality of Life using the following questionnaire: H&N35 scale
Quality of Life [Baseline to 5 years follow up]
Quality of Life using the following questionnaire: Voice Handicap Index (VHI-10)
Quality of Life [Baseline to 5 years follow up]
Quality of Life using the following questionnaire: Neck Dissection Impairment Index (NDII)
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
Feeding tube rate at 1 year [Baseline to 1 year post treatment]
Measure other functional measurements such as feeding tube rate at 1 year
CTCAE Dysphagia Grade [Baseline to 5 years post treatment]
Measure other functional measurements such as CTCAE Dysphagia grade

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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