LCCC 1612: P53 Mutational Status and Circulating Free HPV DNA for the Management of HPV-associated Oropharyngeal Squamous Cell Cancers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 195
- 试验地点
- 4
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
The primary objective of this study is to evaluate whether genomic based risk-stratification can be used in deciding whether to de-intensify in patients with Human Papillomavirus (HPV)-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC) with > 10 pack years smoking history. Hypothesis: Patients with HPV-associated OPSCC, > 10 pack years smoking history, and non-mutated p53 will have similar 2 year progression-free survival (PFS) as patients with < 10 pack years smoking history.
详细描述
The proposed study is a follow-up study to LCCC 1120 and 1413. The investigators have shown that de-intensification is efficacious in these two phase II studies. A major question is whether the investigators can de-intensify in patients with HPV-associated oropharyngeal cancer who have smoking histories. The investigators' hypothesis is that genomic profiling of patients' tumors (specifically for p53 mutations) will help in triaging patients to de-intensification versus standard of care. Patients with HPV-associated OPSCC will be enrolled regardless of smoking history and p53 mutational status will be assessed in patients with a smoking history. The investigators will use the same de-intensification chemoradiotherapy regimen already evaluated in LCCC 1120 and 1413 in patients with HPV-associated OPSCC who have a minimal smoking history and in patients with a smoking history but with wild-type p53. Patients with a smoking history who have mutated p53 will not receive de-intensified chemoradiotherapy, but instead will receive standard doses. The hypothesis is that by using genomics in the patients with a significant smoking history, the investigators will better select those who can be safely de-intensified. Circulating free HPV DNA (cf-HPV-DNA) will also be prospectively assessed from blood samples.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •≥ 18 years of age (no upper age limit)
- •T0-3, N0 to N2c, M0 squamous cell carcinoma of the oropharynx
- •Biopsy proven squamous cell carcinoma that is HPV and/or p16 positive
- •Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to treatment
- •ECOG Performance Status 0-1
- •CBC/differential obtained within 8 weeks prior to treatment, with adequate bone marrow function defined as follows: Platelets ≥ 100,000 cells/mm3; Hemoglobin ≥ 8.0 g/dl
- •Adequate renal and hepatic function within 4 weeks prior to treatment, defined as follows: Serum creatinine < 2.0 mg/dl; Total bilirubin < 2 x the institutional ULN; AST or ALT < 3 x the institutional ULN
- •Negative pregnancy test within 2 weeks prior to treatment for women of childbearing potential
- •Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment and for 6 weeks following treatment.
- •Patients must be deemed able to comply with the treatment plan and follow-up schedule.
- •Patients must provide study specific informed consent prior to study entry
排除标准
- •Prior history of radiation therapy to the head and neck
- •Prior history of head and neck cancer.
- •Unresectable disease (e.g. immobile node on physical exam, nodal disease that radiographically involves the carotid arteries, nerves)
- •Currently taking Disease Modifying Rheumatoid Drugs (DMRDs)
- •Severe, active co-morbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; Transmural myocardial infarction within the last 6 months; Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects (Note, however, coagulation parameters are not required for entry into this protocol); Pre-existing ≥ grade 2 neuropathy; Prior organ transplant; Systemic lupus; Psoriatic arthritis
- •Known HIV positive.
研究组 & 干预措施
Radiotherapy and/or chemotherapy.
Subjects with Oropharyngeal Squamous Cell Carcinoma receiving radiotherapy and/or chemotherapy.
干预措施: Intensity Modulated Radiotherapy (IMRT) (Radiation)
Radiotherapy and/or chemotherapy.
Subjects with Oropharyngeal Squamous Cell Carcinoma receiving radiotherapy and/or chemotherapy.
干预措施: Cisplatin (or alternative) (Drug)
Radiotherapy and/or chemotherapy.
Subjects with Oropharyngeal Squamous Cell Carcinoma receiving radiotherapy and/or chemotherapy.
干预措施: Assessment for surgical evaluation (Procedure)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Two years after completion of the treatment
PFS was assessed as the time from the first day of chemoradiation therapy (CRT) until disease progression. Disease progression was defined as biopsy proven tumor cells. Positron emission tomography / computerized tomography (PET/CT) was performed at week 10-16 (optimally at week 12) after completion of therapy. Biopsies were performed for subjects with imaging or clinical exam results suspicious for tumor. Clinical follow-up occurred and chest imaging was performed during the follow-up.
次要结局
- Local Control Rate(2 years after completion of the treatment)
- Number of Participants With Plasma Circulating Free DNA -3months(3 months after completion of the treatment)
- Number of Participants With Plasma Circulating Free DNA -1 Year(1 year after completion of the treatment)
- Regional Control Rate(2 years post-CRT)
- Number of Participants With Plasma Circulating Free DNA -Baseline(Baseline)
- Number of Participants With Plasma Circulating Free DNA -2 Year(2 years after completion of the treatment)
- Distant Metastasis Free Survival(Two years after completion of the treatment)
- Overall Survival Rate(Up to 2 years after completion of treatment)
- Local-regional Control Rate(2 years after completion of the treatment)