NCT03935672

Brief Summary

The PEARL study will recruit approximately 50 patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) who are about to undergo primary treatment with concurrent chemo-radiation from South Wales (Velindre Cancer Centre and Singleton Hospital, Swansea) and Bristol. The main aim is to see whether it is feasible to preform a positron emission tomography-computed tomography (PET-CT) scan after 2 weeks of radiotherapy and re-plan the radiotherapy based on this PET-CT scan, to re-distribute the dose of radiotherapy being delivered, so that a smaller area of normal tissues in the mouth and throat are treated to a high dose of radiotherapy.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
50

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Jul 2019

Longer than P75 for not_applicable

Geographic Reach
1 country

3 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 3, 2018

Completed
7 months until next milestone

First Posted

Study publicly available on registry

May 2, 2019

Completed
2 months until next milestone

Study Start

First participant enrolled

July 1, 2019

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2021

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2023

Completed
Last Updated

May 2, 2019

Status Verified

April 1, 2019

Enrollment Period

1.7 years

First QC Date

October 3, 2018

Last Update Submit

April 30, 2019

Conditions

Oropharyngeal Cancer

Keywords

Oropharyngeal CancerRadiotherapyHPV positiveAutomated segmentationRadiotherapy re-planning

Outcome Measures

Primary Outcomes (1)

  • Progression free survival at 2 years

    To maintain a high progression free survival rate with biologically adapted radiotherapy in patients with good prognosis HPV positive OPSCC. To be certain that we are not having a negative impact on PFS by adapting the RT plan we will ensure that PFS is at least as high as expected after treatment with chemo-radiotherapy in patients with similarly staged HPV-positive OPSCC.

    2 years following enrolment

Secondary Outcomes (11)

  • Monthly recruitment rate

    End of 2 years recruitment period

  • To test if individualized, adaptive, biologically-based radiotherapy planning is feasible and results in a significant change in the radiotherapy plan.

    2 weeks (10 fractions) of chemo-radiotherapy

  • To test if individualized, adaptive, biologically-based radiotherapy planning results in a significant change in the radiotherapy plan.

    2 weeks (10 fractions) of chemo-radiotherapy

  • To maintain high complete response rates 3 months after treatment

    3 months post treatment

  • Acute toxicity rates

    3 months post treatment

  • +6 more secondary outcomes

Study Arms (1)

All trial participants

OTHER

Baseline plasma and saliva tests for future translational analysis Baseline planning FDG PET CT scan Patients will start their 6 weeks of CCRT within two to three weeks following the planning scans. Cisplatin chemotherapy will be administered. 33 daily fractions of radiotherapy will be delivered over 6 weeks. A second FDG-PET-CT scan (iPET) and repeat plasma and saliva tests will be carried out after 2 weeks of CCRT (on RT days 9 - 12) and the iPET assessed for residual FDG-avid disease. The biological GTV will be re-outlined based on the residual avid region of the tumour on the second PET-CT (bGTV\_iP) At the end of treatment, plasma and saliva tests will be carried out at 4 weeks post treatment and again at the 3 month post-treatment PET-CT Swallowing and QoL assessments will be repeated 4 weeks (+/- 2 weeks) after treatment and will be repeated at 6, 12 and 24 months post-treatment. The plasma and saliva samples will be repeated at 12 and 24 months

Procedure: PET-CT scansProcedure: Outlining the biological GTVs (bGTV_P and bGTV_iP)Procedure: Blood samples for cell-free DNA analysisProcedure: Salivary samples for cell-free DNA analysis

Interventions

PET-CT scansPROCEDURE

Patients will have three scans during the trial. * The 1st scan (prePET) is a baseline diagnostic scan. The patient is in a thermoplastic shell and PET CT will be used by to define a bGTV\_P. bGTV\_P will then be used as an adjunct to help us delineate the GTV\_P. * The 2nd scan (iPET) takes place following 2 weeks (10 fractions) of chemo-radiotherapy. The patient is in a thermoplastic shell and the PET CT will be used to delineate the remaining avid disease (bGTV\_iP). * The 3rd scan takes place 3 months following the last dose of radiotherapy. It will be used to ascertain whether any avid disease remains and may inform the need for further treatment.

All trial participants
Outlining the biological GTVs (bGTV_P and bGTV_iP)PROCEDURE

The biological GTVs (bGTV\_P and bGTV\_iP) will be automatically delineated by ATLAAS and verified manually by a nuclear medicine physician and a clinical oncologist. It will consist of the high FDG uptake volume based on visual assessment whilst using suitable windowing levels. Any differences in contouring will be settled either by the two doctors reaching a consensus or by a third doctor if differences between the first two cannot be resolved.

All trial participants
Blood samples for cell-free DNA analysisPROCEDURE

In order to contribute to our understanding of how disease processes may be monitored in a less invasive and less morbid manner, we will be collecting blood and saliva samples prior to, during, and after the radical treatment of OPSCC in PEARL, to see if there is correlation with disease status and FDG-PET-CT response.

All trial participants
Salivary samples for cell-free DNA analysisPROCEDURE

In order to contribute to our understanding of how disease processes may be monitored in a less invasive and less morbid manner, we will be collecting blood and saliva samples prior to, during, and after the radical treatment of OPSCC in PEARL, to see if there is correlation with disease status and FDG-PET-CT response.

All trial participants

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed squamous cell carcinoma of the oropharynx
  • Positive p16 Immunohistochemistry on local testing
  • UICC TNM (8th edition) stage T1 - T3 N0 - N1 M0
  • Multidisciplinary team (MDT) decision to treat with primary chemoradiotherapy
  • Patients considered fit for radical treatment with primary chemoradiotherapy (including sufficient renal function (GFR\>50ml/min)
  • Aged 18 years or older
  • Not smoked in the last 2 years
  • Written informed consent provided
  • 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. Effective forms of contraception are described in section 15.5.

You may not qualify if:

  • Known HPV negative squamous cell carcinoma of the head and neck
  • T1 - T3 tumours where primary treatment with concomitant chemo-radiotherapy is not considered appropriate
  • T4 disease
  • N2 (TMN8) nodal disease
  • Distant metastatic disease
  • Current smokers or smokers who have stopped within the past 2 years
  • Diabetes mellitus
  • Any pre-existing medical condition likely to impair swallowing function and/ or a history of pre-existing swallowing dysfunction prior to index oropharyngeal cancer
  • Previous radiotherapy to the head and neck
  • History of malignancy in the last 5 years, except basal cell carcinoma of the skin, or carcinoma in situ of the cervix
  • Tumour non-avid on PET-CT or not visible on cross sectional imaging

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Velindre Cancer Center at Velindre Hospital

Cardiff, Wales, CF14 2TL, United Kingdom

Location

Singleton Hospital

Swansea, Wales, SA2 8QA, United Kingdom

Location

University Hospitals Bristol NHS Foundation Trust

Bristol, BS2 8ED, United Kingdom

Location

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Pharyngeal NeoplasmsOtorhinolaryngologic NeoplasmsHead and Neck NeoplasmsNeoplasms by SiteNeoplasmsPharyngeal DiseasesStomatognathic DiseasesOtorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Specimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesSurgical Procedures, OperativeInvestigative Techniques

Study Officials

  • Mererid Evans

    Velindre Cancer Centre

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Martina Svobodova

CONTACT

02920687463svobodovam@cardiff.ac.uk

Lisette Nixon

CONTACT

02920678458pearl@cardiff.ac.uk

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: PEARL is a prospective, interventional, non-randomised, phase II feasibility study for patients with good prognosis Human Papillomavirus (HPV)-associated oropharyngeal squamous cell cancer (OPSCC) who are suitable for treatment with concurrent chemo-radiotherapy (CCRT).
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Senior Trial Manager

Study Record Dates

First Submitted

October 3, 2018

First Posted

May 2, 2019

Study Start

July 1, 2019

Primary Completion

February 28, 2021

Study Completion

February 28, 2023

Last Updated

May 2, 2019

Record last verified: 2019-04

Locations

GB(3)