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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06307015




Registration number
NCT06307015
Ethics application status
Date submitted
1/03/2024
Date registered
12/03/2024
Date last updated
12/03/2024

Titles & IDs
Public title
De-escalation of Radiation Dose in HPV-associated OPC Utilising FMISO PET (DE-RADIATE)
Scientific 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)
Secondary ID [1] 0 0
2023/ETH02441
Universal Trial Number (UTN)
Trial acronym
DE-RADIATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HPV Positive Oropharyngeal Squamous Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - De-escalation
Treatment: Other - Standard of care

Active comparator: Standard of care - Standard of care treatment for patients undergoing definitive chemoradiation for oropharyngeal squamous cell carcinoma

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


Treatment: Other: 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

Treatment: Other: Standard of care
Radiation therapy (70Gy) with concurrent platinum-based chemotherapy to oropharynx + neck
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pathologic complete response
Timepoint [1] 0 0
4 months after completion of radiation therapy
Secondary outcome [1] 0 0
Correlation between MRI and FMISO PET assessment of hypoxia
Timepoint [1] 0 0
Baseline and after 2 weeks of radiation therapy
Secondary outcome [2] 0 0
Quality of Life of patients undergoing de-escalation radiation therapy
Timepoint [2] 0 0
Baseline, then 3 months post completion of treatment, then 3-monthly post to 2 years, then 6-monthly to 5 years
Secondary outcome [3] 0 0
Quality of Life of patients undergoing de-escalation radiation therapy
Timepoint [3] 0 0
Baseline, then 3 months post completion of treatment, then 3-monthly post to 2 years, then 6-monthly to 5 years
Secondary outcome [4] 0 0
Local control
Timepoint [4] 0 0
3-monthly to 2 years, 6-monthly to 5 years
Secondary outcome [5] 0 0
Regional control
Timepoint [5] 0 0
3-monthly to 2 years, 6-monthly to 5 years
Secondary outcome [6] 0 0
Distant metastases
Timepoint [6] 0 0
3-monthly to 2 years, 6-monthly to 5 years
Secondary outcome [7] 0 0
Acute toxicities
Timepoint [7] 0 0
From date of commencement of RT, measured weekly during RT, fortnightly post treatment (up to 3 months post treatment)
Secondary outcome [8] 0 0
Late toxicities
Timepoint [8] 0 0
Commencing from 3 months post treatment and measured 3-monthly to 2 years, then 6-monthly to 5 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/04/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2031
Actual
Sample size
Target
25
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Northern Sydney Cancer Centre, Royal North Shore Hospital - Saint Leonards
Recruitment postcode(s) [1] 0 0
2065 - Saint Leonards

Funding & Sponsors
Primary sponsor type
Other
Name
Royal North Shore Hospital
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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. 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).
Trial website
https://clinicaltrials.gov/study/NCT06307015
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Anna Lawless
Address 0 0
Royal North Shore Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Carol Kwong
Address 0 0
Country 0 0
Phone 0 0
9463 1300
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06307015