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

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

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

Study Overview

• Status: Recruiting
• Conditions: Squamous Cell Carcinoma of the Oropharynx
• Intervention / Treatment: Radiation: De-intensified chemoradiotherapy

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Harvey Quon, MD; Phone Number: 403-521-3619; Email: harvey.quon@ahs.ca
• Study Contact Backup: Name: Kelsey Meyer; Email: Kelsey.Meyer@ahs.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Recruiting
      • Tom Baker Cancer Centre
      • Contact: Harvey Quon, MD; Email: Harvey.Quon@ahs.ca
      • Contact: Kelsey Meyer; Email: Kelsey.Meyer@ahs.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: De-intensified chemoradiotherapy; 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; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time from treatment initiation to death from any cause	Baseline to 5 years
Progression-free survival	Time from treatment initiation to disease progression or death from any cause	Baseline to 5 years
Local, regional, and distant failure rates	Time from treatment initiation to local, regional, and distant failure	Baseline to 5 years
Swallowing function	Measured by fibre-optic endoscopic evaluation of swallowing (FEES) or modified barium swallow (MBS)	12 months
#1 Quality of life	The primary study endpoint is the Xerostomia Questionnaire (XQ), 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.	Baseline to 5 years
#2 Quality of life	Measured by the MD Anderson Symptom Inventory - Head & Neck (MDASI-HN); a questionnaire used to assess the severity of head and neck cancer-related symptoms and their impact on six daily activities (general activity, mood, work, relations with others, walking, and enjoyment of life). Severity of symptoms are assessed on a 0-10 numerical scale, with 0 being "not present" and 10 being "as bad as you can imagine." The ratings can be averaged into several subscale scores: mean core symptom severity (13 core symptom items), mean module symptom severity (additional module symptom items if using a module), mean total symptom severity (13 core symptom items plus additional module symptom items if using a module), and mean interference (6 interference items only). The interference with daily activities is rated on a 0-10 numerical scale, 0 being "did not interfere" and 10 being "interfered completely." The mean of the interference items can be used to represent overall symptom distress.	Baseline to 5 years
#3 Quality of life	Measured by the MD Anderson Dysphagia Inventory (MDADI), which is a 20 item self-administered questionnaire designed for evaluating the impact of dysphagia on the QOL of patients with head and neck cancer. Five responses (strongly agree, agree, no opinion, disagree, and strongly disagree) are available to each question and are scored on a scale of 1 to 5. The MDADI quantifies an individual's global (G), physical (P), emotional (E), and functional (F) perceptions of their swallowing ability. Two summary scores can be obtained: 1) global and 2) composite. The global scale is a single question, which is scored individually to assess the overall impact that swallowing abilities have on QOL. The composite MDADI score summarizes overall performance on remaining 19 items of the MDADI, as a weighted average of the P, E, and F subscales. MDADI scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning).	Baseline to 5 years

Collaborators and Investigators

• Sponsor: AHS Cancer Control Alberta
• Collaborators: Cross Cancer Institute; Tom Baker Cancer Centre
• Investigators: Principal Investigator: Harvey Quon, MD, Tom Baker Cancer Centre

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2021
• Primary Completion (Estimated): October 21, 2028
• Study Completion (Estimated): October 21, 2028

Study Registration Dates

• First Submitted: September 24, 2019
• First Submitted That Met QC Criteria: September 24, 2019
• First Posted (Actual): September 26, 2019

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Oropharyngeal Neoplasms
• Other Study ID Numbers: PROTEcT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No