p16+ Oropharyngeal Cancer Radiation Optimization Trial Reducing Elective Treatment Volumes (PROTEcT)

Study Overview
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Brief Summary
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Volume and Dose De-Intensified Radiotherapy for p16+ Squamous Cell Carcinoma of the Oropharynx: A Multi-Centre, Single Arm Prospective Cohort Study

Detailed Description
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De-intensified radiotherapy to a dose of 60 Gy to the primary tumour and involved lymph nodes and 54 Gy to subclinical regions at risk in 30 fractions. Omission of level IB lymph node regions from the elective nodal volumes. Chemotherapy will be administered as per standard of care, consisting of concurrent cisplatin (high-dose: 100mg/m2 IV every 3 weeks or low-dose: 40mg/m2 IV every week) or cetuximab (at the discretion of medical oncologist).

Official Title
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Volume and Dose De-Intensified Radiotherapy for p16+ Squamous Cell Carcinoma of the Oropharynx: A Multi-Centre, Single Arm Prospective Cohort Study

Conditions
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Squamous Cell Carcinoma of the Oropharynx

Intervention / Treatment
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* Radiation: De-intensified chemoradiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 or older Provide informed consent ECOG performance status 0-2 Histologically confirmed squamous cell carcinoma p16-positive tumor, as determined by immunohistochemistry at local hospital Primary tumor site in the oropharynx (includes tonsil, soft palate, base of tongue, walls of oropharynx) Eligible for curative intent treatment. Smokers and non-smokers are included Tumor stage (AJCC 8th edition): T1 to T3 Nodal stage (AJCC 8th edition): N1 to N2 Adequate bone marrow function, hepatic, and renal function for chemotherapy (Hemoglobin > 80 g/L; Absolute neutrophil count >1.5x109 /L, platelets > 100 x109/L; Bilirubin < 35 umol/L; AST or ALT < 3 x the upper limit of normal; serum creatinine < 130 umol/L or creatinine clearance ≥ 50 ml/min) Exclusion Criteria: - Clinical, radiologic or pathologic Ib nodal involvement (including invasion into submandibular gland) Primary cancer with extension and involvement of the oral cavity Metastatic disease Contraindications to radiotherapy or chemotherapy Prior history of head and neck cancer within 5 years Prior head and neck radiation at any time Inability to attend full course of radiotherapy or follow-up visits Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: De-intensified chemoradiotherapy<br>Radiotherapy to a dose of 60 Gy to the primary tumour and involved lymph nodes and 54 Gy to subclinical regions at risk in 30 fractions. Reduced volume of elective nodal radiation. | Radiation: De-intensified chemoradiotherapy<br>* Radiotherapy to a dose of 60 Gy to the primary tumour and involved lymph nodes and 54 Gy to subclinical regions at risk in 30 fractions. Reduced volume of elective nodal radiation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Xerostomia-related quality of life | Measured by the Xerostomia Questionnaire (XQ), which is an 8 item self-reported xerostomia specific questionnaire. Patients rate each item on an 11 point ordinal Likert scale from 0 to 10, with higher scores indicating greater dryness or discomfort due to dryness. Item scores are added and the sum is transformed linearly to a final summary score ranging between 0 and 100, with higher scores representing greater levels of xerostomia. Based on existing literature, the mean XQ score for patients treated with standard dose and volume radiotherapy is estimated to be 52 (null hypothesis). To detect a clinically meaningful reduction of 11 points in patients treated with volume and dose de-intensified radiotherapy, with a resulting mean XQ score of 41 (alternative hypothesis), with an alpha of 0.05 and 80% power using a one-sided Wilcoxon test assuming normal distribution, 28 patients are required. Accounting for 10% dropout a total sample size of 32 patients is required. | 12 months | 
| Toxicity Criteria for Adverse Events | Measured by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | Baseline to 5 years |