Radiotherapy Dose De-escalation in HPV-Associated Cancers of the Oropharynx

Radiotherapy Dose De-escalation in HPV-Associated Cancers of the Oropharynx Using Metabolic Signature From Interim 18FDG-PET/CT

The purpose of this study is to use intra-treatment 18FDG-PET/CT during definitive radiation therapy for human papillomavirus (HPV)-related oropharyngeal cancer (OPC) as an imaging biomarker to identify and select patients with a favorable response for chemoradiation dose de-escalation. This study will prospectively evaluate the clinical outcomes for patients undergoing dose de-escalation.

Study Overview

• Status: Recruiting
• Conditions: Oropharynx Cancer
• Intervention / Treatment: Radiation: De-escalated radiation dose; Other: 18 fluorodeoxyglucose (FDG)-positron emission tomography (PET)-Computed Tomography (CT); Radiation: Standard radiation dose

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Heather Franklin, BSN, RN, OCN; Phone Number: (919) 668-3726; Email: heather.mccullough@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Contact: Heather Franklin, RN BSN OCN; Phone Number: 919-668-3726; Email: heather.mccullough@duke.edu
      • Principal Investigator: David Brizel, MD
      • Principal Investigator: Yvonne Mowery, MD PhD
    • Raleigh, North Carolina, United States, 27609
      • Recruiting
      • Duke Raleigh Hospital
      • Contact: Heather Franklin, BSN RN OCN; Phone Number: 919-668-3726; Email: heather.mccullough@duke.edu
      • Sub-Investigator: Jessica Lee, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologic documentation of squamous cell carcinoma of the oropharynx with p16-positive immunohistochemical staining and/or positive HPV in situ hybridization (ISH) and/or positive HPV PCR
• Stage I-III (AJCC 8th edition) with plan for concurrent chemotherapy per standard of care treatment
• Zubrod/ECOG score of 0-1
• Weight loss <10% in the 3 months prior to diagnosis
• ≥ 18 years of age
• No prior chemotherapy for their current cancer diagnosis

Exclusion Criteria:

• Prior radiotherapy to the head and neck
• Medical contraindications to radiation therapy
• Absence of gross disease on imaging prior to beginning radiation therapy
• Distant metastatic disease
• Medical contraindication to PET/CT
• History of active cancer other than non-melanoma skin cancer within the last 5 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interim PET-CT with dose de-escalation; Participants will receive an interim PET-CT approximately 2 weeks into radiation therapy.	Radiation: De-escalated radiation dose; Reduced dose of radiation applied to remaining radiation therapy when favorable interim PET-CT signature is produced; Other: 18 fluorodeoxyglucose (FDG)-positron emission tomography (PET)-Computed Tomography (CT); The CT scan - also called computerized tomography or just CT - combines a series of X-ray views taken from many different angles to produce cross-sectional images of the bones and soft tissues inside the body. CT scans in planning radiation therapy are standard of care. A PET is a highly specialized imaging technique that uses short-lived radioactive substances (such as FDG a simple sugar labeled with a radioactive atom) to produce three-dimensional colored images of those substances functioning within the body. These images are called PET scans and the technique is termed PET scanning. PET scanning provides information about the body's chemistry not available through other procedures. Unlike CT or MRI (magnetic resonance imaging), techniques that look at anatomy or body form, PET studies metabolic activity or body function.; Other Names: 18 FDG-PET/CT
Active Comparator: Interim PET-CT with standard radiation	Other: 18 fluorodeoxyglucose (FDG)-positron emission tomography (PET)-Computed Tomography (CT); The CT scan - also called computerized tomography or just CT - combines a series of X-ray views taken from many different angles to produce cross-sectional images of the bones and soft tissues inside the body. CT scans in planning radiation therapy are standard of care. A PET is a highly specialized imaging technique that uses short-lived radioactive substances (such as FDG a simple sugar labeled with a radioactive atom) to produce three-dimensional colored images of those substances functioning within the body. These images are called PET scans and the technique is termed PET scanning. PET scanning provides information about the body's chemistry not available through other procedures. Unlike CT or MRI (magnetic resonance imaging), techniques that look at anatomy or body form, PET studies metabolic activity or body function.; Other Names: 18 FDG-PET/CT; Radiation: Standard radiation dose; Standard dose of radiation applied to remaining radiation therapy when favorable PET-CT signature is not produced

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	defined as the time between initiation of radiation treatment and the first documented recurrence of disease or death due to any cause as measured by medical record abstraction	from initiation of radiation therapy through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
locoregional progression-free survival	as measured by abstraction from the medical record	from initiation of radiation therapy through study completion, an average of 2 years
distant disease-free survival	as measured by abstraction from the medical record	from initiation of radiation therapy through study completion, an average of 2 years
overall survival	as measured by abstraction from the medical record	from initiation of radiation therapy through study completion, an average of 2 years
progression free survival correlation in PET/CT responders versus PET/CT non-responders	as measured by the difference in median Kaplan-Meyer values	2 years
Acute adverse events	as measured by the number of participants who experience dermatitis, mucositis, xerostomia, dysphagia, dysgeusia, neutropenia, thrombocytopenia, nausea, vomiting, renal toxicity, and hearing loss	7 weeks
Long term adverse events	as measured by the number of participants who experience xerostomia, dysphagia, dysgeusia, trismus, lymphedema, superficial soft tissue fibrosis, hypothyroidism and periodontal disease	2 years

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: David Brizel, MD, DUHS

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2021
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: November 19, 2020
• First Submitted That Met QC Criteria: December 8, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Actual): July 5, 2023
• Last Update Submitted That Met QC Criteria: July 3, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: PET-CT
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Oropharyngeal Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: Pro00105899

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: Yes
• product manufactured in and exported from the U.S.: No