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

Study Overview
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Brief Summary
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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.

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

Conditions
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Oropharynx Cancer

Intervention / Treatment
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* Radiation: De-escalated radiation dose
* Radiation: Standard radiation dose
* Other: 18 fluorodeoxyglucose (FDG)-positron emission tomography (PET)-Computed Tomography (CT)


Participation Criteria
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Eligibility Criteria
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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

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: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interim PET-CT with dose de-escalation<br>Participants will receive an interim PET-CT approximately 2 weeks into radiation therapy. | Radiation: De-escalated radiation dose<br>* Reduced dose of radiation applied to remaining radiation therapy when favorable interim PET-CT signature is produced<br>Other: 18 fluorodeoxyglucose (FDG)-positron emission tomography (PET)-Computed Tomography (CT)<br>* 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.<br>* Other names: 18 FDG-PET/CT;|
| Active Comparator: Interim PET-CT with standard radiation<br> | Radiation: Standard radiation dose<br>* Standard dose of radiation applied to remaining radiation therapy when favorable PET-CT signature is not produced<br>Other: 18 fluorodeoxyglucose (FDG)-positron emission tomography (PET)-Computed Tomography (CT)<br>* 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.<br>* Other names: 18 FDG-PET/CT;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PET-CT