Lower-dose radiation for non-hypoxic HPV-positive oropharyngeal cancer guided by FMISO PET
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)
This trial tests whether people with HPV-positive oropharyngeal cancer who show no tumor hypoxia on FMISO PET can be treated safely with a much lower total radiation dose.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 25 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Royal North Shore Hospital Academic / other |
| Drugs / interventions | chemotherapy, radiation |
| Locations | 1 site (Saint Leonards, New South Wales) |
| Trial ID | NCT06307015 on ClinicalTrials.gov |
What this trial studies
Patients with early-stage HPV-positive oropharyngeal cancer or nodal carcinoma of unknown primary will undergo surgical sampling or biopsy and baseline FMISO PET/CT to look for tumor hypoxia. FMISO PET is repeated after 5–10 fractions of radiation to detect persistent or resolving hypoxia, and patients without pre-treatment hypoxia or with intra-treatment resolution are assigned to a de-escalated radiation regimen (total 30 Gy) while others receive standard definitive dosing. The trial measures pathologic complete response after neck dissection, correlates FMISO PET with MRI hypoxia assessment, and tracks acute and late toxicities, quality of life, and local/regional/distant failure rates. Imaging-based hypoxia selection is used to personalise radiation dose with the goal of reducing treatment morbidity without compromising control.
Who should consider this trial
Good fit: Adults (≥18) with p16- and HPV-positive cT1-2N1-2b oropharyngeal squamous cell carcinoma or cTxN1-2 carcinoma of unknown primary who are fit for surgery and/or radiotherapy with ECOG 0–2 are ideal candidates.
Not a fit: Patients whose tumors show pre-treatment or persistent hypoxia on FMISO PET, those with prior high-dose head and neck radiotherapy, or those with poor performance status are unlikely to benefit from de-escalation.
Why it matters
Potential benefit: If successful, this approach could substantially reduce radiation-related side effects and improve quality of life while maintaining cancer control for selected patients.
How similar studies have performed: Previous de-escalation efforts in HPV-positive oropharyngeal cancer have shown promising results in selected patients, but FMISO PET–guided hypoxia-directed dose reduction is relatively novel with limited prospective data.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Saint Leonards, New South Wales
- Northern Sydney Cancer Centre, Royal North Shore Hospital — Saint Leonards, New South Wales, Australia (Recruiting)
Study contacts
- Principal investigator: Anna Lawless — Royal North Shore Hospital
- Study coordinator: Heidi Tsang
- Email: heidi.tsang@health.nsw.gov.au
- Phone: 9463 1300
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.