Circulating Tumor HPV DNA Driven Adjuvant Treatment Deintensification After Transoral Surgery for HPV-Positive Squamous Cell Carcinoma of the Oropharynx
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 4
- 主要终点
- Disease Free Survival
研究概览
简要总结
This study is a prospective phase II trial, designed to assess the efficacy and feasibility of adjuvant treatment deintensification guided by ctHPVDNA levels for patients with HPV+OPSCC who undergo transoral surgery and neck dissection.
详细描述
Oropharyngeal squamous cell carcinoma (OPSCC), commonly known as throat cancer or tonsil cancer, has seen a dramatic rise in incidence over the last twenty years due to the increased incidence of human papillomavirus-positive (HPV) infection and * malignancy within the oropharynx.
The prevailing treatment philosophy within head and neck oncology is that deintensifying treatment could still provide equivalent oncologic outcomes, while further lowering toxicity profiles and improving functional outcomes to minimize the morbidity incurred by patients.
The next frontier in the treatment of HPV+ OPSCC, then, is the potential use of ctHPVDNA in the treatment personalization. Patients could be stratified into risk categories based on their ctHPVDNA levels, and in turn, receive a tailored treatment intensity accordingly.
The goal of this research study is to see if de-intensifying (stopping or scaling back) treatment still provides the same, or perhaps even better, results when compared to standard treatment when using your ctHPVDNA test results as a guide for your treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Pre-Surgery
- •Subjects ≥ 18 years old at the time of informed consent.
- •Ability to provide written informed consent and HIPAA authorization.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Primary tumor of the oropharynx (palatine tonsil, tongue base, soft palate, lateral or posterior walls of oropharynx).
- •Histopathologically confirmed squamous cell carcinoma.
- •Detectable ctHPVDNA from blood samples collected prior to treatment.
- •Resectable and accessible tumor with high probability of achieving negative margins.
- •Smokers and non-smokers included.
- •Tumor stage (AJCC 8th edition): T1 or T2, and select T3 tumors that are mobile and do not invade the larynx.
- •Nodal stage (AJCC 8th edition): N0, N1 or N
- •HPV+ tumor, as determined by p16, in-situ hybridization, real-time polymerase chain reaction, or ctHPVDNA.
- •Post-Surgery
- •Subjects with unknown primaries included if primary is definitively identified and resectable with negative margins or if the palatine and lingual tonsils are thoroughly resected and pathologically proven to be negative for a primary.
排除标准
- •Serious medical condition preventing general anesthesia for surgery.
- •History of previous head and neck radiation or previous head and neck cancer within 3 years.
- •Distant metastatic disease present.
- •Subjects with synchronous HPV+ oropharynx primaries
- •Prior invasive malignant disease within 3 years, with the exception of non-melanoma skin cancer and thyroid cancer, unless patient is deemed cured or disease free, in which case patient may be included in the study.
- •Lactating or pregnant women. Women of childbearing potential must have a negative pregnancy test on the day of surgery. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) unless they meet one of the following criteria:
- •Has undergone a hysterectomy or bilateral oophorectomy; or
- •Has been naturally amenorrheic for at least 12 consecutive months.
研究组 & 干预措施
Observation
Subjects with undetectable postoperative ctHPVDNA levels and either 4 or fewer nodes will have no further adjuvant treatment.
干预措施: NavDx (Diagnostic Test)
Adjuvant Radiation 30 Gray
Subjects with undetectable postoperative ctHPVDNA levels after surgery, negative margins, and five or more positive nodes; or confirmed extranodal extension (ENE) (greater than 2 mm) will undergo deintensified radiation treatment of 30 gray.
干预措施: NavDx (Diagnostic Test)
Adjuvant Radiation 30 Gray
Subjects with undetectable postoperative ctHPVDNA levels after surgery, negative margins, and five or more positive nodes; or confirmed extranodal extension (ENE) (greater than 2 mm) will undergo deintensified radiation treatment of 30 gray.
干预措施: Adjuvant Radiation 30 Gray (Radiation)
Adjuvant Radiation 40 Gray
Subjects with positive postoperative ctHPVDNA will undergo reimaging to evaluate for potentially operable disease, followed by appropriate surgery as indicated. If surgery is performed, repeat ctHPVDNA levels will be checked, and if then negative, subject will be placed in observation or 30 Gy of radiation depending on nodal status.
If repeat ctHPVDNA level is positive, or subject has no obvious operable disease then subject will undergo 40 Gy of radiation.
干预措施: NavDx (Diagnostic Test)
Adjuvant Radiation 40 Gray
Subjects with positive postoperative ctHPVDNA will undergo reimaging to evaluate for potentially operable disease, followed by appropriate surgery as indicated. If surgery is performed, repeat ctHPVDNA levels will be checked, and if then negative, subject will be placed in observation or 30 Gy of radiation depending on nodal status.
If repeat ctHPVDNA level is positive, or subject has no obvious operable disease then subject will undergo 40 Gy of radiation.
干预措施: Adjuvant Radiation 40 Gray (Radiation)
结局指标
主要结局
Disease Free Survival
时间窗: Up to 24 months post initial surgery
Time from surgery to first disease recurrence or death from any cause
次要结局
- Local-reginal Control(Up to 24 months post initial surgery)
- Overall Survival(Up to 24 months post initial surgery)
- Distant metastasis rates(Up to 24 months post initial surgery)
- Adverse Events(up to 6 months post initial surgery)
- Swallowing-related Quality Of Life(3 months, 6 months, 12 months, and 24 months post initial surgery)
- Gastrostomy tube dependence rates(12 and 24 months post intial surgery)
研究者
Michael W. Sim
Associate Professor, Department of Otolaryngology-Head & Neck Surgery
Indiana University