Comparative Effectiveness Trial of Transoral Head and Neck Surgery Followed by Adjuvant Radio(Chemo)Therapy Versus Primary Radiochemotherapy for Oropharyngeal Cancer
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 280
- 试验地点
- 20
- 主要终点
- Time to local or locoregional failure or death from any cause
研究概览
简要总结
Comparative Effectiveness Trial of Transoral Head and Neck Surgery followed by adjuvant Radio(chemo)therapy versus primary Radiochemotherapy for Oropharyngeal Cancer
详细描述
This trial investigates the effectiveness of transoral head and neck surgery (TOS) for locally advanced, but transorally resectable oropharyngeal cancer followed by risk-adapted adjuvant therapy versus primary radiochemotherapy (definitive chemoradiotherapy, CRTX). Both treatments are internationally accepted standards. The choice of the treatment strategy depends on the preference of the responsible attending physician and on the country of residence. Internationally, mostly definitive chemoradiotherapy is regarded as the standard of care for oropharyngeal cancer. In Germany, however, transoral surgical resection is also well established and commonly practiced. The key question therefore is whether one of the two therapies is more effective than the other in clinical daily routine under the given conditions of our health care system and with a realistic, non-ideal patient cohort. For this reason, a comparative effectiveness research (CER) concept will be applied in this setting. The aim of this trial is primarily to show a superiority of the surgical approach in terms of local and locoregional control and secondarily to compare functional outcome and quality of life.
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
- •Histologically proven SCC of the oropharynx; T1, N2a-c, M0; T2, N1-2c, M0; T3, N0-2c, M0, with only amendable to transoral resection)
- •Primary tumor must be resectable through transoral approach
- •p16 immunohistochemitry by local pathology or FFPE tissue must be available for central HPV diagnostic
- •Written and signed informed consent
- •Briefing through surgeon and radiation oncologist
- •ECOG PS ≥2, Karnofsky PS ≥ 60 %
- •Curative treatment intent
- •Adequate bone marrow function: leucocytes > 3.0 x 109/L, neutrophils > 1.5 x 109/L, platelets > 80 x 109/L, hemoglobin > 9.5 g/dL
- •Adequate liver function: Bilirubin < 2.0 g/dL, SGOT, SGPT, < 3 x ULN
- •If of childbearing potential, willingness to use effective contraceptive method for the study duration and 2 months post-dosing.
- •dental examination and appropriate dental therapy if needed prior to Confidential TopROC 2017_03_24 Version 1.0 Seite 15 von 124 beginning of radiotherapy
- •Nutritional evaluation prior to initiation of therapy and optional prophylactic gastrostomy (PEG) tube placement
排除标准
- •Prior invasive malignancy except controlled skin cancer or carcinoma in situ of cervix
- •Unknown primary (CUP), nasopharynx, hypopharynx, laryngeal or salivary gland cancer
- •Metastatic disease
- •Serious co-morbidity, e.g. high-grade carotid artery stenosis, congestive heart failure NYHA grade 3 and 4, liver cirrhosis CHILD C
- •Hemoglobin level <9.5g/dl within 4 weeks before randomization
- •Pregnancy or lactation
- •Women of child-bearing potential with unclear contraception
- •Previous treatment with chemotherapy, radiotherapy, EGFR-targeting agents or surgery exceeding biopsy in head and neck
- •Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study screening
- •Social situations that limit compliance with study requirements or patients with an unstable condition (e.g., psychiatric disorder, a recent history of drug or alcohol abuse, interfering with study compliance, within 6 months prior to screening) or otherwise thought to be unreliable or incapable of complying with the requirements of the protocol
- •Patients institutionalized by official means or court order
- •Deficient
研究组 & 干预措施
Resection/adjuvant radio(-chemo)therapy
- Transoral surgical resection within 4 weeks after randomization
- Neck dissection can be performed during resection of the primary tumor or within 4 weeks after randomization
- 6-7 weeks standard risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy according to arm B if necessary), start within 6 weeks post-surgery
干预措施: Resection (Procedure)
Resection/adjuvant radio(-chemo)therapy
- Transoral surgical resection within 4 weeks after randomization
- Neck dissection can be performed during resection of the primary tumor or within 4 weeks after randomization
- 6-7 weeks standard risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy according to arm B if necessary), start within 6 weeks post-surgery
干预措施: Radiotherapy (Radiation)
Resection/adjuvant radio(-chemo)therapy
- Transoral surgical resection within 4 weeks after randomization
- Neck dissection can be performed during resection of the primary tumor or within 4 weeks after randomization
- 6-7 weeks standard risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy according to arm B if necessary), start within 6 weeks post-surgery
干预措施: Chemotherapy (Drug)
Adjuvant radio(-chemo)therapy/salvage neck dissection
- 6-7 weeks standard radiotherapy (IMRT-technique), start within 4 weeks after randomization
- 70-72 Gy, SIB possible
- Cisplatin 100 mg/m2 on days 1, 22, 43 or Cisplatin once weekly (30-40 mg/m2) on days 1, 8, 15, 22, 29, 36 or Mitomycin C 10 mg/m2 d1, 29 and 5-FU 600 mg/m2/day iv on days 1-5 or Cisplatin 20 mg/m² + 5-FU 600 mg/m²/day iv d 1-5 and 29-33
- +/- Salvage neck dissection 12±2 weeks after treatment
干预措施: Radiotherapy (Radiation)
Adjuvant radio(-chemo)therapy/salvage neck dissection
- 6-7 weeks standard radiotherapy (IMRT-technique), start within 4 weeks after randomization
- 70-72 Gy, SIB possible
- Cisplatin 100 mg/m2 on days 1, 22, 43 or Cisplatin once weekly (30-40 mg/m2) on days 1, 8, 15, 22, 29, 36 or Mitomycin C 10 mg/m2 d1, 29 and 5-FU 600 mg/m2/day iv on days 1-5 or Cisplatin 20 mg/m² + 5-FU 600 mg/m²/day iv d 1-5 and 29-33
- +/- Salvage neck dissection 12±2 weeks after treatment
干预措施: Chemotherapy (Drug)
Adjuvant radio(-chemo)therapy/salvage neck dissection
- 6-7 weeks standard radiotherapy (IMRT-technique), start within 4 weeks after randomization
- 70-72 Gy, SIB possible
- Cisplatin 100 mg/m2 on days 1, 22, 43 or Cisplatin once weekly (30-40 mg/m2) on days 1, 8, 15, 22, 29, 36 or Mitomycin C 10 mg/m2 d1, 29 and 5-FU 600 mg/m2/day iv on days 1-5 or Cisplatin 20 mg/m² + 5-FU 600 mg/m²/day iv d 1-5 and 29-33
- +/- Salvage neck dissection 12±2 weeks after treatment
干预措施: Salvage neck dissection (Procedure)
结局指标
主要结局
Time to local or locoregional failure or death from any cause
时间窗: Defined as time from randomization up to 36 month
The primary objective of this study is to evaluate the effectiveness of primary surgical versus non-surgical treatment of patients with locally advanced, but transorally resectable oropharyngeal cancer in terms of time to local or locoregional failure or death from any cause (LRF).
次要结局
- Quality of life evaluated by patient(Until 3 years after randomization)
- Cost-utility(Until 3 years after randomization)
- Cost-effectiveness(Until 3 years after randomization)
- Effectiveness in terms of morbidity(Until 3 years after randomization)
- Overall survival(Until 3 years after randomization)
- Disease-free survival(Until 3 years after randomization)
- Effectiveness in terms of toxicity(Until 3 years after randomization)