PEARL: PET-based Adaptive Radiotherapy Clinical Trial
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 50
- 试验地点
- 6
- 主要终点
- Progression free survival at 2 years
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •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
研究组 & 干预措施
All trial participants
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
干预措施: PET-CT scans (Procedure)
All trial participants
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
干预措施: Outlining the biological GTVs (bGTV_P and bGTV_iP) (Procedure)
All trial participants
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
干预措施: Blood samples for cell-free DNA analysis (Procedure)
All trial participants
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
干预措施: Salivary samples for cell-free DNA analysis (Procedure)
结局指标
主要结局
Progression free survival at 2 years
时间窗: 2 years following enrolment
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.
次要结局
- Monthly recruitment rate(End of 2 years recruitment period)
- Acute toxicity rates(3 months post treatment)
- 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)
- Late toxicity rates(6, 12 and 24 months post treatment])
- To assess the effect of treatment on swallowing function(3, 6, 12 and 24 months post treatment)
研究者
Lisette Nixon
Senior Trial Manager
Velindre NHS Trust