PEARL: PET-based adaptive radiotherapy clinical trial

ISRCTN	ISRCTN53390753
DOI	https://doi.org/10.1186/ISRCTN53390753
ClinicalTrials.gov (NCT)	NCT03935672
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	42228
Sponsor	Velindre NHS Trust
Funder	Cancer Research Wales; Grant Codes: .12345

Submission date: 22/07/2019
Registration date: 10/09/2019
Last edited: 13/01/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-using-a-scan-to-improve-treatment-for-oropharyngeal-cancer-during-chemoradiotherapy-pearl

Contact information

Dr Ruby Ray
Scientific

Centre for Trials Research
College of Biomedical & Life Sciences
Cardiff University
6th Floor, Neuadd Meirionnydd
Heath Park
Cardiff
CF14 4YS
United Kingdom

Phone	+44 (029) 22510533
Email	pearl@cardiff.ac.uk

Study information

Primary study design	Interventional
Study design	Non-randomised; Interventional; Design type: Treatment, Radiotherapy
Secondary study design	Non randomised study
Study type	Participant information sheet
Scientific title	PEARL: A Phase 1 trial of PET-based adaptive radiotherapy in patients undergoing radical chemoradiotherapy for Human Papilloma Virus (HPV)-positive oropharyngeal cancer.
Study acronym	PEARL
Study objectives	Patients receiving biologically-based adaptive radiotherapy will have comparable two year PFS to patients undergoing standard treatment
Ethics approval(s)	Approved 07/12/2018, Wales research ethics committee 2, Castlebridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB; 02920785738; Wales.REC2@wales.nhs.uk), ref: 18/WA/0391
Health condition(s) or problem(s) studied	Human Papilloma Virus (HPV)-positive oropharyngeal cancer.
Intervention	After informed consent, HPV-positivity will be confirmed by central testing of the diagnostic biopsy specimen. Patients who have had HPV-positivity confirmed locally can undergo baseline assessment of QOL and swallowing function prior to the central laboratory results. Patients will undergo baseline plasma and saliva tests for the presence of biomarkers. Patients will then undergo baseline planning FDG-PET-CT scan which ATLAAS software will use to generate a GTV. The GTV will be reviewed by a team of clinical oncologists who will also take into account the diagnostic MRI, CT and clinical findings on panendoscopy. All patients will undergo swallowing and saliva-sparing RT, delivered using Volumetric Arc Therapy (VMAT) (RapdidArc), which the UK DARS clinical trial team demonstrated reduced RT dose to the pharyngeal constrictors more effectively than IMRT. Patients will start their 6 weeks of CCRT two to three weeks following the planning scans. Cisplatin chemotherapy will be administered as per site-specific protocols. 30 daily fractions of radiotherapy will be delivered over 6 weeks. A second FDG-PET-CT scan and repeat plasma and saliva tests will be carried out after 2 weeks of CRT and the PET assessed for residual FDG-avid disease. The GTV will be re-defined based on the avid region of the tumour. The new GTVb will continue to receive the maximum dose of 66Gy/30F but the non-avid region will receive a total dose of 60Gy/30F. At the end of treatment, plasma and saliva tests will be repeated and will be then carried out on a 4 weekly basis until the 3-month post-treatment PET-CT. Swallowing and QoL assessments will be repeated 4 weeks after treatment. At 3 months post-treatment, a repeat PET-CT will be carried out to look for response. In those patients who have equivocal findings on PET, repeat imaging will be carried out 8 (+/- 2) weeks later to check for resolution. Swallowing panel, QoL assessments, plasma and saliva samples will be repeated at 6, 12 and 24 months posttreatment. The plasma and saliva samples will also be repeated at 18 months. Clinical follow up will be for 5 years as per standard practice.
Intervention type	Other
Primary outcome measure(s)	Progression free survival at 2 years
Key secondary outcome measure(s)	1. Recruitment rates will be monitored annually 2. Percentage reduction in dose to organs at risk (OARs) will be recorded and plans where there was 10% or greater reduction in dose OARs categorised as significantly changed. This will be done after the second PET scan following 2 weeks of chemo radiotherapy treatment 3. Swallowing panel measurements including qualitative and quantitative swallowing assessments (MDADI, PSS-H&N, water swallow test) and feeding tube rate dependency at 1 year 4. Quality of life (QOL) (EORTC QLQ C30, HN35 and UW-QOL questionnaires). QoL will be collected at baseline, 1, 3, 6, 12 and 24 months post concurrent chemo-radiation 5. Acute and late toxicity (NCI CTCAE criteria v4.03). Collected at baseline, weekly during treatment and 3, 6, 12 and 24 months post concurrent chemo-radiation 6. Complete metabolic response rate as per PERCIST criteria on PET-CT scan (postPET) 3 months after treatment
Completion date	31/01/2025

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	50
Key inclusion criteria	1. Histologically confirmed squamous cell carcinoma of the oropharynx 2. Positive p16 Immunohistochemistry on local testing 3. UICC TNM (8th edition) stage T1 – T3 N0 – N1 M0 4. Multidisciplinary team (MDT) decision to treat with primary chemoradiotherapy 5. Patients considered fit for radical treatment with primary chemoradiotherapy 6. Aged 18 years or older 7. Not smoked in the last 2 years 8. Written informed consent provided 9. Patients with reproductive potential (male or female), who are sexually active during the duration of the trial consent to using a highly effective method of contraception for at least six months after the last dose of chemoradiotherapy
Key exclusion criteria	1. Known HPV negative squamous cell carcinoma of the head and neck 2. T1 – T3 tumours where primary treatment with concomitant chemo-radiotherapy is not considered appropriate 3. T4 disease 4. N2 (TMN8) nodal disease 5. Distant metastatic disease 6. Current smokers or smokers who have stopped within the past 2 years 7. Diabetes mellitus 8. Any pre-existing medical condition likely to impair swallowing function and/ or a history of pre-existing swallowing dysfunction prior to index oropharyngeal cancer 9. Previous radiotherapy to the head and neck 10. History of malignancy in the last 5 years, except basal cell carcinoma of the skin, or carcinoma in situ of the cervix 11. Women who are pregnant or breastfeeding and patients with reproductive potential (male or female) who are sexually active during the duration of the trial and do not consent to use highly effective method of contraception for at least 6 months after the last dose of chemoradiotherapy 12. Tumour non-avid on PET-CT or not visible on cross sectional imaging
Date of first enrolment	15/01/2020
Date of final enrolment	30/01/2023

Locations

Countries of recruitment

United Kingdom
England
Wales

Study participating centres

Velindre Cancer Centre

Velindre Road
Cardiff
CF14 2TL
United Kingdom

Abertawe Bro Morgannwg University LHB

One Talbot Gateway
Seaway Drive
Seaway Parade Industrial Estate
Baglan
Port Talbot
SA12 7BR
United Kingdom

University Hospitals Bristol NHS Foundation Trust

Marlborough Street
Bristol
BS1 3NU
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request by contacting the CTR (pearl@cardiff.ac.uk). A process is then followed to ensure request is scientifically credible, within regulatory guidelines and within patient consent. Data may be requested at any pint during the trial. Application approvals will be subject to review by key members including trial Sponsor, TSC, TMG and IDMC where relevant.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

13/01/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/01/2022 to 30/01/2023.
2. The overall trial end date was changed from 31/01/2024 to 31/01/2025.
3. The intention to publish date was changed from 31/01/2024 to 31/01/2025.
30/12/2021: Cancer Research UK plain English summary link added to plain English summary field.
23/03/2021: The following changes were made to the trial record:
1. Recruitment to this study is no longer paused.
2. The recruitment start date was changed from 01/10/2019 to 15/01/2020.
3. The recruitment end date was changed from 01/10/2021 to 30/01/2022.
20/04/2020: Due to current public health guidance, recruitment for this study has been paused.
10/01/2020: ClinicalTrials.gov number added.
08/11/2019: Internal review.
22/07/2019: Trial’s existence confirmed by NIHR