Shortened Course Adjuvant Radiotherapy Following TORS

Phase 2

Recruiting

• Conditions: HPV-Associated Oropharyngeal Squamous Cell Carcinoma
• Interventions: Radiation: Shortened Course Adjuvant Radiotherapy Following TORS

• Registration Number: NCT05714657
• Lead Sponsor: Abramson Cancer Center at Penn Medicine

Brief Summary

This is a single-arm, phase II study to establish the safety of reducing radiation dose in selected HPV-Associated OPSCC patients receiving adjuvant radiation after TORS and neck dissection. This protocol also allows for sparing of the primary resection bed, in appropriate patients, as previously published by our group and found to be safe and effective.

Detailed Description

This is a single-arm Phase II non-inferiority study of adjuvant radiation for locally-advanced HPV-Associated oropharyngeal squamous cell carcinoma. Patients with pT0-T3, N0-N1, M0 disease (per AJCC 8th Edition), detectable pre-operative and undetectable postoperative ctHPVDNA will be eligible. Patients will have undergone TORS primary site resection and neck dissection. Patients will undergo adjuvant RT +/- guideline-indicated chemotherapy. The neck and the primary site will be considered separately.

The primary objective of the study will be to determine the 2-year locoregional control (LRC) rate. Secondary objectives include measures of toxicity (as measured by CTCAE, version 5.0), patient-reported QOL (as measured by the MDASI and MDADI questionnaire), progression-free survival, metastasis-free survival, and overall survival. Differences between patients treated with IMRT and proton therapy in terms of toxicity and QOL will serve as another secondary objective.

Study Timeline

• Study First Submitted: 2022-08-03
• Study Start: 2023-01-30
• Study First Submitted QC: 2023-02-02
• Study First Posted: 2023-02-06
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-03
• Last Update Posted: 2024-07-05
• Primary Completion: 2025-12-31
• Study Completion: 2026-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 104

Inclusion Criteria

• Patients ≥ 18 years old
• Histologically confirmed diagnosis of squamous cell carcinoma of the oropharynx, p16-positive on immunohistochemistry or HPV-positive by In-Situ Hybridization
• Pathologic T0 (unknown primary), T1, T2, or T3 disease (per AJCC 8th Ed)
• Pathologic N0-N1 disease (per AJCC 8th Ed)
• Preoperative plasma ctHPVDNA of ≥ 50 copies/mL
• Undetectable postoperative plasma ctHPVDNA
• ECOG Performance Status 0-1

Exclusion Criteria

• Prior external beam radiation therapy to the head and neck
• Presence of T4 disease
• ≥ 5 positive lymph nodes (which is pathologic N2 disease, per AJCC 8th edition)
• Presence of distant metastatic disease
• Uncontrolled inter-current illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, connective tissue disease or psychiatric illness/social situations that would limit compliance with study requirements.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Shortened Course Adjuvant Radiotherapy	Shortened Course Adjuvant Radiotherapy Following TORS	The volume treated to the regional lymphatics will be according to the characteristics of the primary site and involved lymph nodes. The dose of radiotherapy delivered will be 30 Gy, over the course of 10 treatments (5 daily treatments/week). Treatment of the primary tumor bed will be omitted in appropriate patients, as per the initial TORS de-intensification protocol. In patients requiring treatment of the primary site, reduced dose (30 Gy) will be delivered.

Primary Outcome Measures

Name	Time	Method
Locoregional control	2 years	To determine whether disease recurs locally (at primary site) or in regionally in the nodes of the neck

Secondary Outcome Measures

Name	Time	Method
Progression-free survival	2 Years	To determine progression-free survival (any progression)
Dysphagia, as measured by patient-reported outcome	2 years	To determine patient-reported quality of life (dysphagia) after completion of treatment, as assessed by the MDADI validated questionnaire
Metastasis-free survival	2 years	To determine metastasis-free survival (any distant metastasis)
Overall survival	2 years	To determine overall survival (alive or not)
Quality of life, as measured by patient-reported outcome	2 years	To determine patient-reported quality of life (symptoms) after completion of treatment, as assessed by the MDASI-HN validated questionnaire

Trial Locations

Locations (3)

Lancaster General Hospital; 🇺🇸 Lancaster, Pennsylvania, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Pennsylvania Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States