A Multi-Center Phase II Trial of Individualized Adaptive De-escalated Radiotherapy Using Pre and Mid-Treatment FDG-PET/CT for HPV-related Oropharynx Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 91
- 试验地点
- 4
- 主要终点
- The Percentage of Patients With Local Regional Recurrence (LRR) of Disease
研究概览
简要总结
This prospective study aims to utilize pre- and mid-treatment PET-CT to guide de-escalation of radiation therapy in HPV-related squamous cell carcinoma of the oropharynx.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Patients must have FDG-avid and histologically or cytologically proven squamous cell carcinoma of the oropharynx (tonsil, base of tongue, oropharyngeal wall, soft palate) that is p16 positive by immunohistochemistry or HPV positive by in situ hybridization.
- •AJCC eighth edition staging stage 1 and stage 2
- •Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
- •History/physical examination, including documentation of weight within 4 weeks prior to registration;
- •FDG-PET/CT scan for staging and RT plan within 4 weeks prior to registration;
- •Zubrod Performance Status (A quantification of the functional status of cancer patients that runs from 0 to 5, with 0 denoting perfect health and 5 death) 0-1 within 4 weeks prior to registration;
- •Age ≥ 18;
- •Able to tolerate PET/CT imaging required to be performed
- •CBC/differential obtained within 4 weeks prior to registration on study, with adequate bone marrow function;
- •Serum creatinine within normal institutional limits or a creatinine clearance ≥ 45 ml/min within 4 weeks prior to registration;
- •Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study.
- •The patient must provide study-specific informed consent prior to study entry.
排除标准
- •cT4, cN3 or cM1 disease
- •"Matted nodes" as determined by review with Neuroradiology
- •Gross total excision of both primary and nodal disease with curative intent; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. In other words, to participate in this protocol, the patient must have clinically or radiographically evident gross disease for which disease response can be assessed.
- •Carcinoma of the neck of unknown primary site origin (even if p16 positive);
- •Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
- •Any prior therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable if > 3 years prior to study;
- •Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
- •Severe, active co-morbidity;
- •Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception;
- •Poorly controlled diabetes
研究组 & 干预措施
De-escalation Treatment
Patients will initially receive a single prescription of 70 Gy in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy). If certain parameters are met radiation therapy will be reduced to 54Gy to high risk Planned Target Volume (PTV) and 43.2Gy to low risk PTV all in 27 fractions.
干预措施: Carboplatin (Drug)
Standard Treatment
Patients will receive a single prescription of 70 Gy in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy)
干预措施: Radiation Therapy (Radiation)
De-escalation Treatment
Patients will initially receive a single prescription of 70 Gy in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy). If certain parameters are met radiation therapy will be reduced to 54Gy to high risk Planned Target Volume (PTV) and 43.2Gy to low risk PTV all in 27 fractions.
干预措施: Radiation Therapy (Radiation)
Standard Treatment
Patients will receive a single prescription of 70 Gy in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy)
干预措施: Carboplatin (Drug)
Standard Treatment
Patients will receive a single prescription of 70 Gy in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy)
干预措施: Paclitaxel (Drug)
De-escalation Treatment
Patients will initially receive a single prescription of 70 Gy in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy). If certain parameters are met radiation therapy will be reduced to 54Gy to high risk Planned Target Volume (PTV) and 43.2Gy to low risk PTV all in 27 fractions.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
The Percentage of Patients With Local Regional Recurrence (LRR) of Disease
时间窗: 1 Year
RECIST (Response Evaluation Criteria In Solid Tumors) will be used to evaluate response and recurrence. All patients will be analyzed together as the goal of the study is to estimate risk of LRR in this patient population treated with this particular strategy in which some patients continue to receive standard therapy while others are de-escalated. Results will also be estimated and reported separately for patients receiving standard or de-escalated therapy.
Change in Metabolic Tumor Volume 50% (MTV 50%)
时间窗: 2 months
The change in metabolic tumor volume (MTV)50% at the mid-treatment timepoint will be calculated as percent change from baseline and used as a continuous variable in a Cox model for an outcome of time to LRR. Will also evaluate more non-parametrically, the relation between hazard of LRR and mid-treatment MTV50% using a kernel estimator in a Cox model.
次要结局
- Quality of Life Assessed Per the Functional Assessment of Cancer Therapy-Head and Neck (FACTHN)(2 Years)
- The Proportion of Patients Alive(2 Years)
- Incidence of Toxicity(3, 6, 12 and 24 Months)
- Detectable Circulating Tumor Deoxyribonucleic Acid (ctDNA) in Participants(4 weeks)
- Patterns of Failure(at 3 months and 2 years)
- Overall Survival(at 3 months, and 2 Years)
- Progression- Free Survival(at 3 months and 2 years)
- Incidence of Toxicity(1, 3 and 12 months)
- Detectable Circulating Tumor Deoxyribonucleic Acid (ctDNA) in Participants(from Baseline up to 7 weeks)