Condition category
Cancer
Date applied
22/07/2019
Date assigned
10/09/2019
Last edited
10/09/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Lay summary under review with external organisation

Trial website

https://www.cardiff.ac.uk/centre-for-trials-research/research/studies-and-trials/view/pearl

Contact information

Type

Scientific

Primary contact

Dr Ruby Ray

ORCID ID

Contact details

Centre for Trials Research
College of Biomedical & Life Sciences
Cardiff University
6th Floor
Neuadd Meirionnydd
Heath Park
Cardiff
CF14 4YS
United Kingdom
+44 (029) 22510533
pearl@cardiff.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

42228

Study information

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.

Acronym

PEARL

Study hypothesis

Patients receiving biologically-based adaptive radiotherapy will have comparable two year PFS to patients undergoing standard treatment

Ethics approval

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

Study design

Non-randomised; Interventional; Design type: Treatment, Radiotherapy

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

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

Phase

Drug names

Primary outcome measure

Progression free survival at 2 years

Secondary outcome measures

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

Overall trial start date

01/10/2017

Overall trial end date

31/01/2024

Reason abandoned (if study stopped)

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 50; UK Sample Size: 50

Participant 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

Recruitment start date

01/10/2019

Recruitment end date

01/10/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Velindre Cancer Centre
Velindre Road
Cardiff
CF14 2TL
United Kingdom

Trial participating centre

Abertawe Bro Morgannwg University LHB
One Talbot Gateway Seaway Drive Seaway Parade Industrial Estate Baglan
Port Talbot
SA12 7BR
United Kingdom

Trial participating centre

University Hospitals Bristol NHS Foundation Trust
Marlborough Street
Bristol
BS1 3NU
United Kingdom

Sponsor information

Organisation

Velindre NHS Trust

Sponsor details

Unit 2
Charnwood Court
Heol Billingsley
Cardiff
CF15 7QZ
United Kingdom
+44 (0) 29 2061 5888
sarah.townsend@wales.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Cancer Research Wales; Grant Codes: .12345

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal

IPD sharing statement:
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.

Intention to publish date

31/01/2024

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

22/07/2019: Trial’s existence confirmed by NIHR