The Use of Circulating Biomarkers in Oropharyngeal Cancer and Unknown Primary of Head and Neck - a Prospective Multicenter Study for Treatment Evaluation and Surveillance
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- The accuracy of ctHPV-DNA as a biomarker for recurrent disease, measured in PPV and NPV
研究概览
简要总结
The goal of this observational longitudinal study is to learn about circulating tumor Human Papilloma Virus-DNA (ctHPV-DNA) as a biomarker for HPV positive oropharyngeal cancer and cancer of unknown primary of the head and neck. The main questions it aims to answer are:
- Can ctHPV-DNA be used for treatment evaluation in HPV positive oropharyngeal cancer and cancer of unknown primary of the head and neck?
- Can circulating HPV-DNA be used as a biomarker for recurrent disease during surveillance?
Participants will be asked to leave plasma samples at diagnose, at the end of treatment and at every clinical follow-up.
The patients are there own controls.
详细描述
In the multicenter study of CIRCOS, Circulating biomarkers in oropharyngeal cancer, patients with oropharyngeal cancer or cancer of unknown primary of the head and neck are consecutively included. Plasma samples are collected at diagnosis, at the end of treatment and during surveillance after treatment.
At diagnose participants will fill in informed consent and a form regarding known risk factors for cancer. Tissue from the tumor will be analyzed for HPV genotype with a multiplex q-PCR. Information about p16 will be collected from medical records.
ctHPV-DNA are short DNA fragments that leaks into the blood stream from tumor cells during apoptosis and necrosis. In the study, ctHPV-DNA will be extracted from blood plasma. Levels of ctHPV-DNA (copies/mL) will be measured using digital droplet PCR (ddPCR) with genotype specific assays (based on the result of q-PCR at diagnose) used in singleplex (SAGA diagnostics). A negative sample after treatment will be defined as a good molecular response for evaluation after treatment. Two consecutive, positive samples during surveillance will be defined as molecular recurrence. If a molecular recurrence is seen patients will be contacted and offered an extra clinical control at an Ear nose and throat department.
If a patient is HPV negative in tissue, the tissue will be analyzed with whole genome sequencing. If a mutation is found, a personalized ddPCR-kit will be used for plasma.
All patients will be followed for five years.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Oropharyngeal cancer
- •Cancer of unknown primary in the head and neck
排除标准
- •Previous treatment of cancer in the oropharynx.
- •Previous treatment of unknown primary tumor.
- •Remote metastases
- •Patients unwilling or unable to comply with the study protocol and follow-up schedule
结局指标
主要结局
The accuracy of ctHPV-DNA as a biomarker for recurrent disease, measured in PPV and NPV
时间窗: 5 year follow-up
ctHPV-DNA will be evaluated by ddPCR. Two consecutive positive values will be defined as a molecular recurrance. The accuracy of the test will be presented with negative predictive value (NPV) and positive predictive value (PPV) at one, two (interim analysis) and at five year follow-up
次要结局
- A comparison between molecular (copies/mL) and radiological response to treatment according to RECIST (Response Evaluation Criteria in Solid Tumors) using Kruskal wallis test.(3 months follow-up)
- The correlation between molecular tumor burden (copies/mL) and radiological tumor burden (diameter and volume) using Kendall rank correlation coefficient.(3 months follow-up)