Swallowing Outcomes and Circulating Tumor DNA in Patients With HPV Related Oropharyngeal Cancer Treated With Transoral Surgery and Reduced Intensity Adjuvant Therapy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 15
- 试验地点
- 3
- 主要终点
- MD Anderson Dysphagia Index (MDADI)
研究概览
简要总结
This is a non-randomized, open-label phase II clinical trial that studies the effect of reduced dose radiation therapy and chemotherapy after surgery in treating patients with human papillomavirus (HPV) caused throat cancer. Giving reduced dose radiation therapy and chemotherapy after surgery may improve quality of life compared with standard of care primary chemoradiation approach without compromising survival.
详细描述
PRIMARY OBJECTIVE:
I. To measure swallowing function and disease specific quality of life of patients with oropharyngeal cancer treated with transoral surgery and reduced intensity adjuvant therapy.
SECONDARY OBJECTIVES:
I. To examine kinetics of circulating tumor deoxyribonucleic acid (DNA) in patients treated with transoral surgery.
II. To estimate local control, progression free and overall survival using transoral surgery and reduced intensity adjuvant therapy.
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
- •Histologically proven squamous cell carcinoma of the oropharynx
- •Clinical stage T1-2, N0-N3, M0 by American Joint Committee on Cancer (AJCC) 8 criteria
- •Must have tumors deemed surgically resectable with acceptable morbidity
- •Estimated life expectancy of at least 12 weeks
- •Must give informed consent
- •Must have Eastern Cooperative Oncology Group (ECOG) performance status =< 3
- •Must have detectable circulating HPV DNA levels
- •Platelets >= 100,000/ul
- •Absolute neutrophil count (ANC) >= 1,500/ul
- •Hemoglobin > 8 g/dl (use of transfusion to achieve this is acceptable)
- •Total bilirubin < 2 X institutional upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 3 X institutional ULN
- •Serum creatinine < 2 x institutional ULN or creatinine clearance > 50 ml/min as determined by 24 hour collection or estimated by Cockcroft-Gault formula
- •Negative pregnancy test, if applicable
排除标准
- •Patients may not have received previous therapy for their head and neck squamous cell carcinoma (SCC), including chemotherapy, radiation therapy, or surgery beyond biopsy
- •Second primary malignancy. Exceptions are:
- •Patient had a second primary malignancy but has been treated and disease free for at least 3 years
- •In situ carcinoma (e.g. in situ carcinoma of the cervix)
- •Non-melanomatous carcinoma of the skin
- •Patients with metastatic disease beyond the neck will be excluded
- •Serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator
- •Age < 18 years
- •Patients with human immunodeficiency virus (HIV) infection are not automatically excluded, but must meet the following criteria: CD4 count is > 499/cu mm and their viral load is < 50 copies/ml. Use of highly active antiretroviral therapy (HAART) is allowed
- •Grade 3-4 electrolyte abnormalities (Common Terminology Criteria for Adverse Events [CTCAE], version [v.] 5)
- •Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or > 12.5 mg/dl (> 3.1 mmol/L) despite intervention to normalize levels
- •Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite intervention to normalize levels
- •Potassium < 3.0 mmol/L or > 6 mmol/L despite intervention to normalize levels
- •Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels
- •Women who are pregnant, due to the teratogenic effects of radiation therapy and chemotherapy on the unborn fetus. Women of childbearing age must agree to undergo a pregnancy test prior to therapy and to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 6 months after. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- •Tumor deemed unresectable with acceptable morbidity:
- •Tumors > 4 cm in size (T3 or higher)
- •Tumors of the base of tongue < 4 cm but with deep invasion of tongue musculature placing hypoglossal nerve or both lingual arteries at risk
- •Significant extension into hypopharynx
- •Extension into soft palate beyond 1/3 of the width
- •Clinically extensive extranodal extension (ENE) e.g. radiologic evidence of invasion of carotid artery, gross extension into sternocleidomastoid muscle or deep neck muscles.
- •Lymph nodes larger than 6 cm without clinical ENE will be allowed
研究组 & 干预措施
GROUP III - High Risk Recurrence (transoral surgery, EBRT 60Gy, cisplatin 30 mg/m2)
Patients whose tumor has a "positive margin", which means the tumor could not be removed with healthy tissue around it or tumor grows significantly outside the lymph node will undergo EBRT RT 60 Gy for 6 weeks and receive cisplatin intravenously (IV) weekly 30mg/m2 for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: University of Washington Quality of Life Questionnaire (Other)
GROUP III - High Risk Recurrence (transoral surgery, EBRT 60Gy, cisplatin 30 mg/m2)
Patients whose tumor has a "positive margin", which means the tumor could not be removed with healthy tissue around it or tumor grows significantly outside the lymph node will undergo EBRT RT 60 Gy for 6 weeks and receive cisplatin intravenously (IV) weekly 30mg/m2 for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Cisplatin (Drug)
GROUP I - Low Risk Recurrence (transoral surgery, clinical observation))
After standard of care transoral surgery, patients whose small tumor was removed completely and have only one lymph node involved will undergo clinical observation.
干预措施: Transoral Surgery (Procedure)
GROUP I - Low Risk Recurrence (transoral surgery, clinical observation))
After standard of care transoral surgery, patients whose small tumor was removed completely and have only one lymph node involved will undergo clinical observation.
干预措施: Incisional Tumor Biopsy (Procedure)
GROUP I - Low Risk Recurrence (transoral surgery, clinical observation))
After standard of care transoral surgery, patients whose small tumor was removed completely and have only one lymph node involved will undergo clinical observation.
干预措施: Circulating tumor deoxyribonucleic acid (ctDNA) levels assessment (Other)
GROUP I - Low Risk Recurrence (transoral surgery, clinical observation))
After standard of care transoral surgery, patients whose small tumor was removed completely and have only one lymph node involved will undergo clinical observation.
干预措施: MD Anderson Dysphagia Index (Other)
GROUP I - Low Risk Recurrence (transoral surgery, clinical observation))
After standard of care transoral surgery, patients whose small tumor was removed completely and have only one lymph node involved will undergo clinical observation.
干预措施: University of Washington Quality of Life Questionnaire (Other)
GROUP I - Low Risk Recurrence (transoral surgery, clinical observation))
After standard of care transoral surgery, patients whose small tumor was removed completely and have only one lymph node involved will undergo clinical observation.
干预措施: Euro-QOL 5 dimension scale questionnaire (Other)
GROUP I - Low Risk Recurrence (transoral surgery, clinical observation))
After standard of care transoral surgery, patients whose small tumor was removed completely and have only one lymph node involved will undergo clinical observation.
干预措施: Modified barium swallow (MBS) evaluation with aspiration-penetration scale (Diagnostic Test)
GROUP II - Medium Risk Recurrence (transoral surgery, EBRT 50Gy)
Patients whose tumor was removed completely but has certain features that make it more likely to come back such as growth around the nerves or into the vessels, or has more than one lymph nodes involved, will undergo external body radiation therapy (EBRT) RT 50Gy for 5 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Transoral Surgery (Procedure)
GROUP II - Medium Risk Recurrence (transoral surgery, EBRT 50Gy)
Patients whose tumor was removed completely but has certain features that make it more likely to come back such as growth around the nerves or into the vessels, or has more than one lymph nodes involved, will undergo external body radiation therapy (EBRT) RT 50Gy for 5 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: External Beam Radiation Therapy (Radiation)
GROUP II - Medium Risk Recurrence (transoral surgery, EBRT 50Gy)
Patients whose tumor was removed completely but has certain features that make it more likely to come back such as growth around the nerves or into the vessels, or has more than one lymph nodes involved, will undergo external body radiation therapy (EBRT) RT 50Gy for 5 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Incisional Tumor Biopsy (Procedure)
GROUP II - Medium Risk Recurrence (transoral surgery, EBRT 50Gy)
Patients whose tumor was removed completely but has certain features that make it more likely to come back such as growth around the nerves or into the vessels, or has more than one lymph nodes involved, will undergo external body radiation therapy (EBRT) RT 50Gy for 5 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Circulating tumor deoxyribonucleic acid (ctDNA) levels assessment (Other)
GROUP II - Medium Risk Recurrence (transoral surgery, EBRT 50Gy)
Patients whose tumor was removed completely but has certain features that make it more likely to come back such as growth around the nerves or into the vessels, or has more than one lymph nodes involved, will undergo external body radiation therapy (EBRT) RT 50Gy for 5 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: MD Anderson Dysphagia Index (Other)
GROUP II - Medium Risk Recurrence (transoral surgery, EBRT 50Gy)
Patients whose tumor was removed completely but has certain features that make it more likely to come back such as growth around the nerves or into the vessels, or has more than one lymph nodes involved, will undergo external body radiation therapy (EBRT) RT 50Gy for 5 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: University of Washington Quality of Life Questionnaire (Other)
GROUP II - Medium Risk Recurrence (transoral surgery, EBRT 50Gy)
Patients whose tumor was removed completely but has certain features that make it more likely to come back such as growth around the nerves or into the vessels, or has more than one lymph nodes involved, will undergo external body radiation therapy (EBRT) RT 50Gy for 5 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Euro-QOL 5 dimension scale questionnaire (Other)
GROUP II - Medium Risk Recurrence (transoral surgery, EBRT 50Gy)
Patients whose tumor was removed completely but has certain features that make it more likely to come back such as growth around the nerves or into the vessels, or has more than one lymph nodes involved, will undergo external body radiation therapy (EBRT) RT 50Gy for 5 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Modified barium swallow (MBS) evaluation with aspiration-penetration scale (Diagnostic Test)
GROUP III - High Risk Recurrence (transoral surgery, EBRT 60Gy, cisplatin 30 mg/m2)
Patients whose tumor has a "positive margin", which means the tumor could not be removed with healthy tissue around it or tumor grows significantly outside the lymph node will undergo EBRT RT 60 Gy for 6 weeks and receive cisplatin intravenously (IV) weekly 30mg/m2 for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Transoral Surgery (Procedure)
GROUP III - High Risk Recurrence (transoral surgery, EBRT 60Gy, cisplatin 30 mg/m2)
Patients whose tumor has a "positive margin", which means the tumor could not be removed with healthy tissue around it or tumor grows significantly outside the lymph node will undergo EBRT RT 60 Gy for 6 weeks and receive cisplatin intravenously (IV) weekly 30mg/m2 for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: External Beam Radiation Therapy (Radiation)
GROUP III - High Risk Recurrence (transoral surgery, EBRT 60Gy, cisplatin 30 mg/m2)
Patients whose tumor has a "positive margin", which means the tumor could not be removed with healthy tissue around it or tumor grows significantly outside the lymph node will undergo EBRT RT 60 Gy for 6 weeks and receive cisplatin intravenously (IV) weekly 30mg/m2 for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Incisional Tumor Biopsy (Procedure)
GROUP III - High Risk Recurrence (transoral surgery, EBRT 60Gy, cisplatin 30 mg/m2)
Patients whose tumor has a "positive margin", which means the tumor could not be removed with healthy tissue around it or tumor grows significantly outside the lymph node will undergo EBRT RT 60 Gy for 6 weeks and receive cisplatin intravenously (IV) weekly 30mg/m2 for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Circulating tumor deoxyribonucleic acid (ctDNA) levels assessment (Other)
GROUP III - High Risk Recurrence (transoral surgery, EBRT 60Gy, cisplatin 30 mg/m2)
Patients whose tumor has a "positive margin", which means the tumor could not be removed with healthy tissue around it or tumor grows significantly outside the lymph node will undergo EBRT RT 60 Gy for 6 weeks and receive cisplatin intravenously (IV) weekly 30mg/m2 for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: MD Anderson Dysphagia Index (Other)
GROUP III - High Risk Recurrence (transoral surgery, EBRT 60Gy, cisplatin 30 mg/m2)
Patients whose tumor has a "positive margin", which means the tumor could not be removed with healthy tissue around it or tumor grows significantly outside the lymph node will undergo EBRT RT 60 Gy for 6 weeks and receive cisplatin intravenously (IV) weekly 30mg/m2 for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Euro-QOL 5 dimension scale questionnaire (Other)
GROUP III - High Risk Recurrence (transoral surgery, EBRT 60Gy, cisplatin 30 mg/m2)
Patients whose tumor has a "positive margin", which means the tumor could not be removed with healthy tissue around it or tumor grows significantly outside the lymph node will undergo EBRT RT 60 Gy for 6 weeks and receive cisplatin intravenously (IV) weekly 30mg/m2 for 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Modified barium swallow (MBS) evaluation with aspiration-penetration scale (Diagnostic Test)
结局指标
主要结局
MD Anderson Dysphagia Index (MDADI)
时间窗: At baseline.
MDADI is a 20 item quality of life instrument specifically focusing on swallowing aspects. It was originally designed for head and neck cancer patients and has been widely used and validated in this population. The total score ranges from 20 to 100 with the higher score indicating higher level of function.
MD Anderson Dysphagia Index (MDADI)
时间窗: At 24 weeks post completion of therapy.
MDADI is a 20 item quality of life instrument specifically focusing on swallowing aspects. It was originally designed for head and neck cancer patients and has been widely used and validated in this population. The total score ranges from 20 to 100 with the higher score indicating higher level of function.
MD Anderson Dysphagia Index (MDADI)
时间窗: At 1 year post completion of therapy.
MDADI is a 20 item quality of life instrument specifically focusing on swallowing aspects. It was originally designed for head and neck cancer patients and has been widely used and validated in this population. The total score ranges from 20 to 100 with the higher score indicating higher level of function.
次要结局
- Correlation of circulating tumor deoxyribonucleic acid (ctDNA) levels with known adverse pathological features(At baseline and at 4 weeks post-surgery)
- Penetration-Aspiration Score on Modified Barium Swallow examination(Baseline and 1 year post completion of therapy)
- Locoregional control.(At 3 years post completion of therapy)
- Disease free survival.(At 3 years post completion of therapy)
- Progression free survival.(At 3 years post completion of therapy)
- Overall survival.(At 3 years post completion of therapy)
- University of Washington Quality of Life Questionnaire(At baseline, 24 weeks and 1 year post completion of therapy)
- European Quality of Life Five Dimension Five Level Scale Questionnaire scores(At baseline, 24 weeks, and 1 year post completion of therapy)
- Rate of gastrostomy tube dependence(At baseline, 24 weeks, and 1 year post completion of therapy)
研究者
Dylan Roden, MD MPH
Assistant Professor
Rutgers, The State University of New Jersey