Stereotactic Boost and SHOrt-course Radiation Therapy for HPV-associated OroPharynx Cancer Trial: A Randomized Multicentric Phase III Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 360
- 试验地点
- 3
- 主要终点
- Progression free survival
研究概览
简要总结
This is a randomized clinical trial comparing the outcomes of short-course chemoradiation consisting in stereotactic boost to the gross tumor and de-esclalated chemoradiation to the elective neck in human papilloma associated oropharynx cancer vs. the current standard 7-week course chemoradiation.
详细描述
Concurrent platinum-based chemoradiation remains the standard of care in locally advanced head and neck cancer. The current standard radiation regimen consists in a 7-week course of conventionally fractionated radiotherapy to the gross tumor volume (GTV), along with bilateral prophylactic neck irradiation to an elective dose of ~ 50 Gy in 2 Gy per fraction. In addition to being cumbersome, the current protracted daily radiation course is associated with high rates of acute and late toxicities and significant deterioration of patients' quality of life. In the light of the remarkably improved prognosis of the distinct subgroup of HPV-OPC, there is growing interest for treatment de-intensification strategies in contemporaneous OPC cohorts.
Stereotactic ablative radiotherapy (SABR) allows for ultra-precise delivery of ablative radiation dose over a small number of fractions, by combining sharp dose gradients with use of optimal image guidance. The increased conformity and reduced margins used in SABR can substantially reduce the dose to surrounding organs at risk and could therefore reduce toxicity. In addition, previous work has shown that an elective dose of 40 Gy in 2 Gy per fraction, in conjunction with chemotherapy, is sufficient for microscopic sterilisation of cancer cells and can translate into a reduction of toxicities.
The goal of this trial is to compare the efficacy and safety of short-course chemoradiation consisting in stereotactic boost to the gross tumor of 14 Gy in 2 fractions followed by de-esclalated chemoradiation (40 Gy in 20 fractions and concurrent 2 cycles of Cisplatin 100mg/m2) in human papilloma associated oropharynx cancer vs. the current standard 7-week course chemoradiation (70 Gy in 33 fractions with 2-3 cycles of Cisplatin 100mg/m2).
This is an open label randomized phase III non inferiority trial. Patients will be randomized using a 1:1 ratio between the standard and the experimental arm and will be stratified by tumor stage and use of concurrent chemotherapy.
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
- •Ability to provide written informed consent.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Biopsy proven diagnosis of squamous cell carcinoma of the oropharynx.
- •Positive for HPV by p16 immunohistochemistry (IHC) or HPV in-situ hybridization (ISH)
- •Clinical stage T1-3, N1 M0 (Stage I-II) as per AJCC 8th edition.
- •Primary tumor < 30 cc
- •Planned for curative chemoradiation
- •For females of child-bearing age, a negative pregnancy test
排除标准
- •Clinical N3 classification, as per AJCC 8th edition
- •Clinically overt extranodal extension (ENE). As per AJCC 8th edition, clinically overt ENE is defined as invasion of the skin, infiltration of musculature/fixation to adjacent structures on clinical examination, cranial nerve, brachial plexus, sympathetic trunk or phrenic nerve invasion with dysfunction).
- •Previous irradiation of the head and neck region
- •Previous surgery of the HNC region (except for incisional or excisional biopsies)
- •Pregnancy or breastfeeding
- •Connective tissue disease
- •Any medical condition that could, in the opinion of the investigator, prevent follow-up after radiotherapy.
- •Non-Cisplatin concurrent chemotherapy
- •Prior induction chemotherapy
结局指标
主要结局
Progression free survival
时间窗: 2 years after the end of chemoradiation
Patient alive with no local, regional or distant recurrence at 2 years after the end of chemoradiation
次要结局
- Subacute toxicity(Between 2 and 6 months after the end of chemoradiation)
- Acute toxicity(Less than 2 months after the end of chemoradiation)
- Late toxicity(Between 6 months and 5-years after the end of chemoradiation)
- OS(At 2- and 5-years after the end of chemoradiation)
- locoregional control(At 2- and 5-years after the end of chemoradiation)
- Head and neck symptom burden(At baseline, and 1-, 3-, 6-, 12- months post-treatment, and yearly from years 2-5 after the end of chemoradiation)
- Dysphagia(At baseline, and 1-, 3-, 6-, 12- months post-treatment, and yearly from years 2-5 after the end of chemoradiation)
- Time from treatment start to return to work(Measured in days and reported at 2-years post-treatment)
研究者
Houda Bahig
Radiation Oncologist
Centre hospitalier de l'Université de Montréal (CHUM)