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

Head and Neck Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04220749
• Other study ID #: ORATOR 3
• Status: Recruiting
• Phase: Phase 2
• Start date: June 25, 2020
• Est. completion date: February 2028

Study information

• Verified date: September 2020
• Source: Lawson Health Research Institute
• Contact: Susan Archer
• Phone: 519-685-8618
• Email: susan.archer[@]lhsc.on.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 68
• Est. completion date: February 2028
• Est. primary completion date: February 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Oropharyngeal Squamous Cell Carcinoma

Intervention

Radiation:
• Radiation
Standard of Care: Radiation +/- Chemotherapy

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

Locations

Country	Name	City	State
Canada	London Regional Cancer Program	London	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Lawson Health Research Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-Specific Survival	Time from randomization to death from cancer	5 years
Secondary	Overall Survival	Time from randomization to death from any cause	5 years
Secondary	Progression-Free Survival	Defined as time from randomization to death from any cause	5 years
Secondary	Local-Regional Failure	Defined as time from randomization to first local-regional failure (analyzed as cumulative incidence function with death as competing event)	5 years
Secondary	Distant Failure	Defined as time from randomization to first distant failure or metastasis (analyzed as cumulative incidence function with death as competing event)	5 years
Secondary	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)	5 years
Secondary	Quality of Life	Quality of Life using the following questionnaire: MD Anderson Dysphagia Inventory (MDADI)	Baseline to 5 years follow up
Secondary	Quality of Life	Quality of Life using the following questionnaire: EORTC QLQ-C30	Baseline to 5 years follow up
Secondary	Quality of Life	Quality of Life using the following questionnaire: H&N35 scale	Baseline to 5 years follow up
Secondary	Quality of Life	Quality of Life using the following questionnaire: Voice Handicap Index (VHI-10)	Baseline to 5 years follow up
Secondary	Quality of Life	Quality of Life using the following questionnaire: Neck Dissection Impairment Index (NDII)	Baseline to 5 years follow up
Secondary	Quality of Life	Quality of Life using the following questionnaire: Patient Neurotoxicity Questionnaire (PNQ)	Baseline to 5 years follow up
Secondary	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	Randomization until 5 years follow up
Secondary	Feeding tube rate at 1 year	Measure other functional measurements such as feeding tube rate at 1 year	Baseline to 1 year post treatment
Secondary	CTCAE Dysphagia Grade	Measure other functional measurements such as CTCAE Dysphagia grade	Baseline to 5 years post treatment