HPV Positive Oropharyngeal Squamous Cell CarcinomaDE-RADIATENCT06307015
De-escalation of Radiation Dose in HPV-associated OPC Utilising FMISO PET (DE-RADIATE)
A study testing De-escalation in people with HPV Positive Oropharyngeal Squamous Cell Carcinoma, run by Royal North Shore Hospital at 1 site in Australia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HPV Positive Oropharyngeal Squamous Cell Carcinoma
- What is being tested?
- De-escalation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteAustralia
- Study dates
- 1 Apr 2025to Dec 2031
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Carolyn Kwong contact
Australia1 site, 1 recruiting
- Recruiting
Northern Sydney Cancer Centre, Royal North Shore Hospital
Saint Leonards, New South Wales, 2065
Carol Kwong, 9463 1300, carolyn.kwong@health.nsw.gov.au
Anna Lawless
About this study
Official title: 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:
Read more
- What is the pathologic complete response rate in patients selected for radiation dose de-escalation and neck dissection?
- What is the correlation between MRI and FMISO PET assessment of hypoxia before and during RT?
- What are the acute and late toxicities in patients selected for radiation dose de-escalation?
- What are the quality of life scores in patients selected for radiation dose de-escalation?
- 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).
Read the 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.
- Being tested
- De-escalation, Standard of care
- Keywords
- Radiation therapy, De-escalation, FMISO PET, Hypoxia
- Medical subject headings
- Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
De-escalationRadiation
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
Standard of careRadiation
Radiation therapy (70Gy) with concurrent platinum-based chemotherapy to oropharynx + neck
| Study group | Role | What they receive |
|---|---|---|
| Standard of care | Active comparator | Standard of care treatment for patients undergoing definitive chemoradiation for oropharyngeal squamous cell carcinoma Receives: Radiation: Standard of care |
| De-escalation | Experimental | 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 Receives: Radiation: De-escalation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic complete response
Pathologic complete response in surgical neck dissection
Measured: 4 months after completion of radiation therapy
Secondary outcomes (8)
Correlation between MRI and FMISO PET assessment of hypoxia
Correlation between MRI and FMISO PET assessment of hypoxia at baseline and during radiation therapy
Measured: Baseline and after 2 weeks of radiation therapy
Quality of Life of patients undergoing de-escalation radiation therapy
Quality of Life - Global (assessment by EORTC QLQ-30)
Measured: 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
Quality of Life - Head \& Neck Specific (assessment by EORTC HN-35)
Measured: Baseline, then 3 months post completion of treatment, then 3-monthly post to 2 years, then 6-monthly to 5 years
Local control
Failure rate at primary site (oropharynx) (calculated from date of commencing RT)
Measured: 3-monthly to 2 years, 6-monthly to 5 years
Regional control
Failure rate in neck (calculated from date of commencing RT)
Measured: 3-monthly to 2 years, 6-monthly to 5 years
Distant metastases
Number of participants with radiologically confirmed distant metastases (calculated from date of commencing RT)
Measured: 3-monthly to 2 years, 6-monthly to 5 years
Acute toxicities
Acute toxicities of radiation therapy +/- chemotherapy (assessed by CTCAE V 5.0)
Measured: From date of commencement of RT, measured weekly during RT, fortnightly post treatment (up to 3 months post treatment)
Late toxicities
Acute toxicities of radiation therapy +/- chemotherapy (assessed by CTCAE V 5.0)
Measured: Commencing from 3 months post treatment and measured 3-monthly to 2 years, then 6-monthly to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2024
- Study start1 Apr 2025
- Primary completionDec 2027 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HPV Positive Oropharyngeal Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal North Shore Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anna Lawless, Royal North Shore Hospital
- Investigators
- Anna Lawless, Principal investigator, Royal North Shore HospitalSarah Bergamin, Principal investigator, Royal North Shore Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06307015
- Sponsor's protocol ID
- 2023/ETH02441
- Acronym
- DE-RADIATE
- Status last verified
- Apr 2025
- First submitted
- 1 Mar 2024
- Last updated
- 30 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT06307015
- Acronym / sponsor ID
- DE-RADIATE / 2023/ETH02441
- Keywords
- Radiation therapy, De-escalation, FMISO PET, Hypoxia
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Royal North Shore HospitalUniversity, hospital or other
- Study start
- 1 Apr 2025 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2031 (estimated)
- First posted
- 12 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- What is the pathologic complete response rate in patients selected for radiation dose de-escalation and neck dissection?
- What is the correlation between MRI and FMISO PET assessment of hypoxia before and during RT?
- What are the acute and late toxicities in patients selected for radiation dose de-escalation?
- What are the quality of life scores in patients selected for radiation dose de-escalation?
- 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).
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of care | Active comparator | Radiation: Standard of careStandard of care treatment for patients undergoing definitive chemoradiation for oropharyngeal squamous cell carcinoma |
| De-escalation | Experimental | Radiation: De-escalationDe-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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| De-escalationSurgical 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 | Radiation | De-escalation |
| Standard of careRadiation therapy (70Gy) with concurrent platinum-based chemotherapy to oropharynx + neck | Radiation | Standard of care |
Primary outcome
Pathologic complete response
Time frame: 4 months after completion of radiation therapy
Pathologic complete response in surgical neck dissection
8 secondary outcomes
Correlation between MRI and FMISO PET assessment of hypoxia
Time frame: 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 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
Local control
Time frame: 3-monthly to 2 years, 6-monthly to 5 years
Regional control
Time frame: 3-monthly to 2 years, 6-monthly to 5 years
Distant metastases
Time frame: 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)
Late toxicities
Time frame: Commencing from 3 months post treatment and measured 3-monthly to 2 years, then 6-monthly to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Carolyn Kwong contact
Anna Lawless principal investigator
Royal North Shore Hospital
Sarah Bergamin principal investigator
Royal North Shore Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing De-escalation in people with HPV Positive Oropharyngeal Squamous Cell Carcinoma, run by Royal North Shore Hospital at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Heidi Tsang (9463 1300, heidi.tsang@health.nsw.gov.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic complete response (time frame: 4 months after completion of radiation therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2025.