A Randomized Trial of Treatment De-Escalation for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: Radiotherapy vs. Trans-Oral Surgery (ORATOR II)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 61
- 试验地点
- 9
- 主要终点
- Overall Survival
研究概览
简要总结
The goal of this randomized treatment de-escalation study is to formally compare outcomes in HPV related oropharyngeal cancer tumors treated with a primary radiotherapy versus a primary surgical approach, to provide a high level of evidence to guide the selection of treatment options for a subsequent phase III trial
详细描述
The goal of this randomized treatment de-escalation study is to formally compare outcomes in HPV related oropharyngeal cancer tumors treated with a primary radiotherapy versus a primary surgical approach, to provide a high level of evidence to guide the selection of treatment options for a subsequent phase III trial
The study will compare overall survival rates relative to historical controls for de-intensified primary radiotherapy [60 GY +/- chemotherapy] versus transoral surgery (TOS) and neck dissection [+/- adjuvant 50Gy radiotherapy] in patients with early T-stage HPV-positive squamous cell carcinoma of the oropharynx and to compare quality of life (QOL) profiles.
The study will require a sample size of 140 patients randomized in a 1:1 ratio between the two arms. Arm 1 (radiotherapy +/1 chemotherapy) and Arm 2 (TOS)
Patients will be followed for a total of 5 years
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Age 18 years or older
- •willing to provide informed consent
- •ECOG performance status 0-2
- •Histologically confirmed squamous cell carcinoma
- •P16 positive, or HPV positive
- •Primary tumor site in the oropharynx (includes tonsil, soft palate, base of tongue, walls of oropharynx)
- •Eligible for curative intent treatment, with likely negative resection margins at surgery. For patients where adequate transoral access is in question, they will first undergo an examination under anesthesia prior to randomization to ensure adequate exposure can be obtained.
- •Smokers and non-smokers are included. Patients will be stratified by ,<10 pack years smoking history versus > or equal to 10 pack years.
- •Tumor stage (AJCC 8th edition): T1 or T2
- •Nodal stage (AJCC 8th edition): N0, N1, or N2
- •For patients who may require chemotherapy (ie, patients with multiple lymph nodes positive or a single node more than 3 cm in size, in any plane, CBC/differential within 4 weeks prior to randomization with adequate bone marrow function, hepatic, and renal function defined as: Hemoglobin ≥ 80 g/L; Absolute neutrophil count ≥ 1.5 x 10 9/L, platelets ≥ 100 x 10 9/L, bilirubin ≤ 35 umol/L, AST or ALT ≤ 3 x the upper limit of normal; serum creatinine ≤ 130 umol/L or creatinine clearance ≥ 50 ml/min
- •patients assessed at head and neck multidisciplinary clinic (with assessment by radiation oncologist and surgeon) and presented at multidisciplinary tumor board prior to randomization
排除标准
- •unambiguous clinical or radiological evidence of extranodaal extension on pre-treatment imaging. This includes the presence of matted notes, defined as 3 or more nodes that are abutting with loss of intervening fat planes
- •Serious medical comorbidities or other contraindications to radiotherapy, chemotherapy or surgery
- •prior history of head and neck cancer within 5 years
- •prior head and neck radiation at any time
- •metastatic disease
- •inability to attend full course of radiotherapy or follow up visits
- •prior invasive malignant disease unless disease-free for at least 5 years or more, with the exception of non-melanoma skin cancer
- •pregnant or lactating women
研究组 & 干预措施
Arm 1, Radiation +/- Chemotherapy
Standard Treatment (Radiation +/- Chemotherapy)
干预措施: Radiation (Radiation)
Arm 2, TOS + Neck Dissection
Transoral Surgery (TOS) + Neck Dissection (plus radiation, if required)
干预措施: Transoral Surgery (TOS) + Neck Dissection (Procedure)
结局指标
主要结局
Overall Survival
时间窗: 2 years
Time from randomization to death from any cause
次要结局
- CTCAE Dysphagia grade(baseline to 5 years post treatment)
- Speech intelligibility(baseline to 5 years post treatment)
- Progression free survival comparison with historical controls(5 years)
- Quality of Life 1 year post treatment(1 year post treatment)
- Feeding tube rate at 1 year(baseline to 1 year post treatment)
- toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4(Randomization until 5 years follow up)
- Normalcy of diet(baseline to 5 years post treatment)
- 2 year progression-free survival comparison between Arm 1 and Arm 2(2 years)
- Quality of life(Baseline to 5 years follow up)