De-escalation of Radiation Dose in HPV-associated OPC Utilising FMISO PET (DE-RADIATE) (DE-RADIATE)

July 25, 2025 updated by: Anna Lawless, Royal North Shore Hospital

De-escalation of Radiation Dose in HPV-associated Oropharyngeal Squamous Cell Carcinoma Utilising FMISO PET and Magnetic Resonance Imaging as Non-Invasive Biomarkers of Hypoxia (DE-RADIATE)

The goal of this prospective clinical trial is to determine if HPV-associated oropharyngeal squamous cell carcinoma that is non-hypoxic on FMISO PET can be successfully treated with a lower dose of radiation therapy.

The main questions it aims to answer are:

  1. What is the pathologic complete response rate in patients selected for radiation dose de-escalation and neck dissection?
  2. What is the correlation between MRI and FMISO PET assessment of hypoxia before and during RT?
  3. What are the acute and late toxicities in patients selected for radiation dose de-escalation?
  4. What are the quality of life scores in patients selected for radiation dose de-escalation?
  5. What are the local, regional and distant failure rates of patients selected for radiation dose de-escalation?

Patients with cT1-2N1-2b (AJCC 7th edition) oropharyngeal tumours will undergo surgical resection of the primary tumour. Following this, they will be allocated to standard radiation therapy (70Gy with concurrent cisplatin chemotherapy) or de-escalation radiation therapy (30Gy with concurrent cisplatin chemotherapy) based on the results of FMISO PET. Patients with non-hypoxic tumours at baseline OR after two weeks of radiation therapy will be allocated to the de-escalated group. 3-4 months after completion of radiation therapy, all patients in the de-escalated group will undergo mandatory neck dissection to assess pathologic response.

Researchers will assess the pathologic response rate after surgery in the de-escalation group. They will also compare the outcomes (oncological outcomes and quality of life) between the group receiving the standard treatment (70Gy) and the group receiving de-escalated radiation therapy (30Gy).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study is designed to evaluate the role of FMISO PET in selecting patients for de-escalated RT. Patients with cT1-2N-1-2b HPV+ OPC or cTxN1-2 CUP, who are suitable for surgical management of the primary (if applicable) and/or RT to the primary and ipsilateral neck will be included. All patients will undergo surgical resection or core biopsy of the primary site if applicable (negative margins and robotic surgery not mandated) or EUA and tonsillectomy (CUP) and FNA or core biopsy of the cervical lymph node (all patients). Patients will be eligible for inclusion if histopathology is consistent with HPV-associated squamous cell carcinoma or CUP, with p16 positivity (IHC) and HPV positivity (PCR).

Patients enrolled will undergo FMISO PET/CT (after surgery to the primary or EUA/biopsy of suspected primary site) to assess for tumour hypoxia, which will stratify patients into two groups. Determination for the presence or absence of hypoxia will be made on the basis of visual inspection and in accordance with well-established tumour-muscle activity ratio (>1.2) on the late static 18F-FMISO PET by 1 nuclear medicine physician. FMISO PET will be repeat after 5-10 fractions of RT (1-2 weeks of treatment) with the same assessment for hypoxia.

Absence of pre-treatment hypoxia or intra-treatment resolution of hypoxia on FMISO PET will be deemed as an indicator of radiosensitivity and qualify a patient for de-escalation (i.e., to total dose 30Gy). The remainder of patients (i.e., with evidence of tumour hypoxia at the FMISO PET performed after 5-10 fractions of RT) will continue to standard of care RT to a total dose of 70Gy.

Additional MRI images (including T1, T2 and dynamic contract-enhanced and oxygen enhanced sequences) before and during RT (at the same time as 18F FMISO PET). These will not change the patient's management.

All patients will undergo routine FDG-PET/CT scan three months after RT (as part of standard of care). Patients in the de-escalation arm will undergo mandatory ipsilateral neck dissection within 3-4 months of completing RT to assess for pathologic response. Patients will be followed up for a minimum of five years post treatment.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
25

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • Saint Leonards, New South Wales, Australia, 2065
        • Recruiting
        • Northern Sydney Cancer Centre, Royal North Shore Hospital
        • Contact:
        • Principal Investigator:
          • Anna Lawless
        • Principal Investigator:
          • Sarah Bergamin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age > 18 years
  • Histologically confirmed cT1-2N1-2b oropharyngeal squamous cell carcinoma or cTxN1-2 carcinoma of unknown primary
  • p16 positive (70% nuclear and cytoplasmic staining) and HPV positive (genotyping via PCR) tumours of the tonsil, base of tongue, glossotonsillar sulcus, or unknown primary site (suspected mucosal origin).
  • No contraindications to radiotherapy, platinum-based chemotherapy or surgery
  • No contraindications to PET/CT or MRI
  • Eastern Cooperative Oncology Group (ECOG) performance status score 0-2 (KPS > 70%)
  • Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

  • Women lactating, pregnant or of childbearing potential who are not willing to avoid pregnancy during the study
  • Patients with a history of severe renal disease(s) (eGFR <20) than cannot tolerate gadolinium chelate contrast agents.)
  • ECOG ≥ 3
  • Previous high dose radiation therapy to the head or neck
  • Patients unwilling or unable to have PET/CT or MRI
  • Geographically remote patients unable to agree to imaging schedule
  • Patients with a history of psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study.
  • Patients with significant cardiac or pulmonary disease including cardiac arrythmias or Chronic Obstructive Pulmonary Disease (COPD) that are unable to tolerate high flow O2 for oxygen contrast.
  • Patients taking carbonic anhydrase inhibitors (acetazolamide)
  • History of glaucoma
  • Any implant, foreign body, 3T MRI incompatible device, or other contraindication to MRI imaging

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Standard of care
Standard of care treatment for patients undergoing definitive chemoradiation for oropharyngeal squamous cell carcinoma
Radiation: Standard of care
Radiation therapy (70Gy) with concurrent platinum-based chemotherapy to oropharynx + neck
Experimental: De-escalation
De-escalated radiation therapy for patients undergoing surgery to the primary site followed by chemoradiation to the primary site and neck for oropharyngeal squamous cell carcinoma
Radiation: De-escalation
Surgical resection of primary oropharyngeal tumour followed by de-escalated radiation therapy (30Gy) with concurrent platinum-based chemotherapy to oropharynx + neck, followed by surgical neck dissection

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pathologic complete response
Time Frame: 4 months after completion of radiation therapy
Pathologic complete response in surgical neck dissection
4 months after completion of radiation therapy

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Correlation between MRI and FMISO PET assessment of hypoxia
Time Frame: Baseline and after 2 weeks of radiation therapy
Correlation between MRI and FMISO PET assessment of hypoxia at baseline and during radiation therapy
Baseline and after 2 weeks of radiation therapy
Quality of Life of patients undergoing de-escalation radiation therapy
Time Frame: Baseline, then 3 months post completion of treatment, then 3-monthly post to 2 years, then 6-monthly to 5 years
Quality of Life - Global (assessment by EORTC QLQ-30)
Baseline, then 3 months post completion of treatment, then 3-monthly post to 2 years, then 6-monthly to 5 years
Quality of Life of patients undergoing de-escalation radiation therapy
Time Frame: Baseline, then 3 months post completion of treatment, then 3-monthly post to 2 years, then 6-monthly to 5 years
Quality of Life - Head & Neck Specific (assessment by EORTC HN-35)
Baseline, then 3 months post completion of treatment, then 3-monthly post to 2 years, then 6-monthly to 5 years
Local control
Time Frame: 3-monthly to 2 years, 6-monthly to 5 years
Failure rate at primary site (oropharynx) (calculated from date of commencing RT)
3-monthly to 2 years, 6-monthly to 5 years
Regional control
Time Frame: 3-monthly to 2 years, 6-monthly to 5 years
Failure rate in neck (calculated from date of commencing RT)
3-monthly to 2 years, 6-monthly to 5 years
Distant metastases
Time Frame: 3-monthly to 2 years, 6-monthly to 5 years
Number of participants with radiologically confirmed distant metastases (calculated from date of commencing RT)
3-monthly to 2 years, 6-monthly to 5 years
Acute toxicities
Time Frame: From date of commencement of RT, measured weekly during RT, fortnightly post treatment (up to 3 months post treatment)
Acute toxicities of radiation therapy +/- chemotherapy (assessed by CTCAE V 5.0)
From date of commencement of RT, measured weekly during RT, fortnightly post treatment (up to 3 months post treatment)
Late toxicities
Time Frame: Commencing from 3 months post treatment and measured 3-monthly to 2 years, then 6-monthly to 5 years
Acute toxicities of radiation therapy +/- chemotherapy (assessed by CTCAE V 5.0)
Commencing from 3 months post treatment and measured 3-monthly to 2 years, then 6-monthly to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Royal North Shore Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Anna Lawless, Royal North Shore Hospital
  • Principal Investigator: Sarah Bergamin, Royal North Shore Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 1, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 6, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 12, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 30, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 25, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2023/ETH02441

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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