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PEARL PET-based Adaptive Radiotherapy Clinical Trial (PEARL)

Primary Purpose

Oropharyngeal Cancer

Status
Unknown status
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
PET-CT scans
Outlining the biological GTVs (bGTV_P and bGTV_iP)
Blood samples for cell-free DNA analysis
Salivary samples for cell-free DNA analysis
Sponsored by
Velindre NHS Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oropharyngeal Cancer focused on measuring Oropharyngeal Cancer, Radiotherapy, HPV positive, Automated segmentation, Radiotherapy re-planning

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 (including sufficient renal function (GFR>50ml/min)
  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. Effective forms of contraception are described in section 15.5.

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. Tumour non-avid on PET-CT or not visible on cross sectional imaging

Sites / Locations

  • Velindre Cancer Center at Velindre Hospital
  • Singleton Hospital
  • University Hospitals Bristol NHS Foundation Trust

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

All trial participants

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Monthly recruitment rate
As this is a feasibility study, recruitment will be monitored and monthly recruitment rate over 2 years will be presented.
To test if individualized, adaptive, biologically-based radiotherapy planning is feasible and results in a significant change in the radiotherapy plan.
Percentage reduction in mean dose to OAR (superior pharyngeal constrictor muscles, contralateral parotids, contralateral submandibular gland, salivary glands) as a result of PET-CT during treatment. Percentage change to PTV will also be presented.
To test if individualized, adaptive, biologically-based radiotherapy planning results in a significant change in the radiotherapy plan.
Percentage reduction in mean dose to OAR (superior pharyngeal constrictor muscles, contralateral parotids, contralateral submandibular gland, salivary glands) as a result of PET-CT during treatment. Percentage change to PTV will also be presented.
To maintain high complete response rates 3 months after treatment
The proportion of patients who are complete metabolic responders at 3 months as per PERCIST criteria will be presented.
Acute toxicity rates
Cumulative acute CTCAE toxicity score percentages during and up to 3 months after treatment will be presented.
Late toxicity rates
Water swallow test will be plotted over time, scores will be presented at 6, 12, 18 and 24 months.
Late toxicity rates
MDADI will be plotted over time, scores will be presented at 6, 12, 18 and 24 months.
Late toxicity rates
QoL scores will be plotted over time, scores will be presented at 6, 12, 18 and 24 months.
To assess the effect of treatment on swallowing function
Water swallow test scores will be plotted over time.
To assess the effect of treatment on swallowing function
MDADI scores will be plotted over time.
To assess the effect of treatment on swallowing function
QoL scores will be plotted over time.

Full Information

First Posted
October 3, 2018
Last Updated
April 30, 2019
Sponsor
Velindre NHS Trust
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1. Study Identification

Unique Protocol Identification Number
NCT03935672
Brief Title
PEARL PET-based Adaptive Radiotherapy Clinical Trial
Acronym
PEARL
Official Title
PEARL: PET-based Adaptive Radiotherapy Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Unknown status
Study Start Date
July 1, 2019 (Anticipated)
Primary Completion Date
February 28, 2021 (Anticipated)
Study Completion Date
February 28, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Velindre NHS Trust

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
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). The incidence of oropharyngeal squamous cell carcinoma (OPSCC) caused by Human Papillomavirus (HPV) infection (HPV-positive OPSCC) is increasing in the United Kingdom. It tends to affect younger patients and has a better outcome than most other head and neck cancers. A large proportion of patients diagnosed with HPV-positive OPSCC will undergo non-surgical treatment. This usually involves 6 to 7 weeks of chemo-radiotherapy, with chemotherapy being given weekly or during the first and fourth week of the radiotherapy course (CCRT). Many patients with HPV-positive OPSCC are cured of their disease but often have to live for several decades with the side effects of their treatment. Side effects from radiotherapy are usually caused because normal tissues surrounding the cancer receive radiation whilst the cancer itself is being treated. Positron emission tomography-computed tomography (PET-CT) scans are able to look at the metabolic (or biological) activity of cells and are currently recommended in the UK for response assessment after a patient has completed radiotherapy for a head and neck cancer but, as far as we know, have not yet been used routinely to adapt radiotherapy according to the individual patient's response during radiotherapy. PEARL will explore the feasibility of individually adapting the radiotherapy plan for each patient after 2 weeks of radical CCRT, based on biological changes in tumour activity seen on an interim FDG-PET-CT scan, carried out early on during a course of treatment. The aim is to reduce the dose of radiotherapy received by surrounding normal tissues to ultimately reduce toxicity. The study will establish the progression free survival rate (PFS) in patients who receive biologically adapted radiotherapy. Furthermore, it will also explore whether changes seen on PET-CT scan during treatment correlate with outcome and with changes in potential blood-based biomarkers of response. Toxicity rates will be assessed, particularly the effect of treatment on swallowing function.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oropharyngeal Cancer
Keywords
Oropharyngeal Cancer, Radiotherapy, HPV positive, Automated segmentation, Radiotherapy re-planning

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
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).
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
All trial participants
Arm Type
Other
Arm Description
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
Intervention Type
Procedure
Intervention Name(s)
PET-CT scans
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Outlining the biological GTVs (bGTV_P and bGTV_iP)
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Blood samples for cell-free DNA analysis
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Salivary samples for cell-free DNA analysis
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression free survival at 2 years
Description
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.
Time Frame
2 years following enrolment
Secondary Outcome Measure Information:
Title
Monthly recruitment rate
Description
As this is a feasibility study, recruitment will be monitored and monthly recruitment rate over 2 years will be presented.
Time Frame
End of 2 years recruitment period
Title
To test if individualized, adaptive, biologically-based radiotherapy planning is feasible and results in a significant change in the radiotherapy plan.
Description
Percentage reduction in mean dose to OAR (superior pharyngeal constrictor muscles, contralateral parotids, contralateral submandibular gland, salivary glands) as a result of PET-CT during treatment. Percentage change to PTV will also be presented.
Time Frame
2 weeks (10 fractions) of chemo-radiotherapy
Title
To test if individualized, adaptive, biologically-based radiotherapy planning results in a significant change in the radiotherapy plan.
Description
Percentage reduction in mean dose to OAR (superior pharyngeal constrictor muscles, contralateral parotids, contralateral submandibular gland, salivary glands) as a result of PET-CT during treatment. Percentage change to PTV will also be presented.
Time Frame
2 weeks (10 fractions) of chemo-radiotherapy
Title
To maintain high complete response rates 3 months after treatment
Description
The proportion of patients who are complete metabolic responders at 3 months as per PERCIST criteria will be presented.
Time Frame
3 months post treatment
Title
Acute toxicity rates
Description
Cumulative acute CTCAE toxicity score percentages during and up to 3 months after treatment will be presented.
Time Frame
3 months post treatment
Title
Late toxicity rates
Description
Water swallow test will be plotted over time, scores will be presented at 6, 12, 18 and 24 months.
Time Frame
6, 12 and 24 months post treatment
Title
Late toxicity rates
Description
MDADI will be plotted over time, scores will be presented at 6, 12, 18 and 24 months.
Time Frame
6, 12 and 24 months post treatment]
Title
Late toxicity rates
Description
QoL scores will be plotted over time, scores will be presented at 6, 12, 18 and 24 months.
Time Frame
6, 12 and 24 months post treatment]
Title
To assess the effect of treatment on swallowing function
Description
Water swallow test scores will be plotted over time.
Time Frame
3, 6, 12 and 24 months post treatment
Title
To assess the effect of treatment on swallowing function
Description
MDADI scores will be plotted over time.
Time Frame
3, 6, 12 and 24 months post treatment
Title
To assess the effect of treatment on swallowing function
Description
QoL scores will be plotted over time.
Time Frame
3, 6, 12 and 24 months post treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Martina Svobodova
Phone
02920687463
Email
svobodovam@cardiff.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Lisette Nixon
Phone
02920678458
Email
pearl@cardiff.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mererid Evans
Organizational Affiliation
Velindre Cancer Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Velindre Cancer Center at Velindre Hospital
City
Cardiff
State/Province
Wales
ZIP/Postal Code
CF14 2TL
Country
United Kingdom
Facility Name
Singleton Hospital
City
Swansea
State/Province
Wales
ZIP/Postal Code
SA2 8QA
Country
United Kingdom
Facility Name
University Hospitals Bristol NHS Foundation Trust
City
Bristol
ZIP/Postal Code
BS2 8ED
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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PEARL PET-based Adaptive Radiotherapy Clinical Trial

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