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

• ClinicalTrials.gov Identifier: NCT04667585
• Recruitment Status: Recruiting
• First Posted: December 14, 2020
• Last Update Posted: July 5, 2023
• Sponsor: Duke University
• Information provided by (Responsible Party): Duke University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Oropharynx Cancer	Radiation: De-escalated radiation dose; Radiation: Standard radiation dose; Other: 18 fluorodeoxyglucose (FDG)-positron emission tomography (PET)-Computed Tomography (CT)	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants undergo either reduced radiation dose or standard radiation dose based on the metabolic signature from an Interim 18FDG-PET/CT
• Masking: Single (Participant)
• Primary Purpose: Other
• Official Title: Radiotherapy Dose De-escalation in HPV-Associated Cancers of the Oropharynx Using Metabolic Signature From Interim 18FDG-PET/CT
• Actual Study Start Date: April 12, 2021
• Estimated Primary Completion Date: April 2027
• Estimated Study Completion Date: April 2027

Arms and Interventions

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 Name: 18 FDG-PET/CT
Active Comparator: Interim PET-CT with standard radiation	Radiation: Standard radiation dose; Standard dose of radiation applied to remaining radiation therapy when favorable PET-CT signature is not 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 Name: 18 FDG-PET/CT

Outcome Measures

Primary Outcome Measures :

1. Progression-free survival [ Time Frame: from initiation of radiation therapy through study completion, an average of 2 years ]
   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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Heather Franklin, BSN, RN, OCN; (919) 668-3726; heather.mccullough@duke.edu

Locations

United States, North Carolina

Duke University Medical Center; Recruiting

Durham, North Carolina, United States, 27710

Contact: Heather Franklin, RN BSN OCN 919-668-3726 heather.mccullough@duke.edu

Principal Investigator: David Brizel, MD

Principal Investigator: Yvonne Mowery, MD PhD

Duke Raleigh Hospital; Recruiting

Raleigh, North Carolina, United States, 27609

Contact: Heather Franklin, BSN RN OCN 919-668-3726 heather.mccullough@duke.edu

Sub-Investigator: Jessica Lee, MD

Sponsors and Collaborators

Duke University

Investigators

• Principal Investigator: David Brizel, MD; DUHS

More Information

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT04667585
• Other Study ID Numbers: Pro00105899
• First Posted: December 14, 2020
• Last Update Posted: July 5, 2023
• Last Verified: July 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Duke University:

PET-CT

Additional relevant MeSH terms:

Oropharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Fluorodeoxyglucose F18; Radiopharmaceuticals; Molecular Mechanisms of Pharmacological Action