Clinical trial NCT03935672: PEARL PET-based Adaptive Radiotherapy Clinical Trial
Official title: PEARL: PET-based Adaptive Radiotherapy Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Oropharyngeal Cancer
Keywords: Oropharyngeal Cancer
Radiotherapy
HPV positive
Automated segmentation
Radiotherapy re-planning
Lead sponsor: Velindre NHS Trust
Sponsor class: OTHER_GOV
First posted: 2019-05-02
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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).
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival at 2 years
timeFrame: 2 years following enrolment
Secondary outcomes:
measure: Monthly recruitment rate
timeFrame: End of 2 years recruitment period
measure: To test if individualized, adaptive, biologically-based radiotherapy planning is feasible and results in a significant change in the radiotherapy plan.
timeFrame: 2 weeks (10 fractions) of chemo-radiotherapy
measure: To test if individualized, adaptive, biologically-based radiotherapy planning results in a significant change in the radiotherapy plan.
timeFrame: 2 weeks (10 fractions) of chemo-radiotherapy
measure: To maintain high complete response rates 3 months after treatment
timeFrame: 3 months post treatment
measure: Acute toxicity rates
timeFrame: 3 months post treatment
measure: Late toxicity rates
timeFrame: 6, 12 and 24 months post treatment
measure: Late toxicity rates
timeFrame: 6, 12 and 24 months post treatment]
measure: Late toxicity rates
timeFrame: 6, 12 and 24 months post treatment]
measure: To assess the effect of treatment on swallowing function
timeFrame: 3, 6, 12 and 24 months post treatment
measure: To assess the effect of treatment on swallowing function
timeFrame: 3, 6, 12 and 24 months post treatment
measure: To assess the effect of treatment on swallowing function
timeFrame: 3, 6, 12 and 24 months post treatment
Other outcomes:
Locations:
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Swansea
country: United Kingdom
facility: Singleton Hospital
state: Wales
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust
Study officials:
affiliation: Velindre Cancer Centre
name: Mererid Evans
role: PRINCIPAL_INVESTIGATOR
References: