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De-escalation of Radiation Dose in HPV-associated OPC Utilising FMISO PET (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 details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2024-04-01
Primary completion: 2027-12-01
Study completion finish: 2031-12-01
Study type
TREATMENT
Phase
NA
Trial ID
NCT06307015
Intervention or treatment
RADIATION: De-escalation
RADIATION: Standard of care
Conditions
- • HPV Positive Oropharyngeal Squamous Cell Carcinoma
Find a site
Closest Location:
Northern Sydney Cancer Centre, Royal North Shore Hospital
Research sites nearby
Select from list below to view details:
Northern Sydney Cancer Centre, Royal North Shore Hospital
Saint Leonards, New South Wales, Australia
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?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
ACTIVE_COMPARATOR: Standard of care
| RADIATION: Standard of care
|
EXPERIMENTAL: De-escalation
| RADIATION: De-escalation
|
What is the study measuring?
Primary outcome
| Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
|---|---|---|
| Pathologic complete response | Pathologic complete response in surgical neck dissection | 4 months after completion of radiation therapy |
Secondary outcome
| Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
|---|---|---|
| Correlation between MRI and FMISO PET assessment of hypoxia | 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 | 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 | 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 | Failure rate at primary site (oropharynx) (calculated from date of commencing RT) | 3-monthly to 2 years, 6-monthly to 5 years |
| Regional control | Failure rate in neck (calculated from date of commencing RT) | 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) | 3-monthly to 2 years, 6-monthly to 5 years |
| Acute toxicities | 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 | 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 |
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