A Pilot Study of Adaptive De-Intensified Radiotherapy Using Circulating Tumor DNA in HPV- Associated Oropharyngeal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Positron emission tomography complete response
研究概览
简要总结
This phase II trial studies how well using circulating tumor deoxyribonucleic acid (DNA) to guide lower dose radiation therapy works in treating patients with human papillomavirus infection (HPV)-associated oropharyngeal cancer. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Recently, a blood test has been developed to detect the human papillomavirus in the blood and determine how many viral particles are present. Researchers want to compare any good and bad effects of using the lower dose radiation therapy with chemotherapy compared to the usual standard of care dose chemotherapy in patients who clear the human papillomavirus particles from their blood.
详细描述
PRIMARY OBJECTIVE:
I. To estimate the 3-month post-treatment positron emission tomography (PET) response rate in patients who have a favorable tumor tissue modified viral (TTMV) tumor profile (defined as >= 200 copies/mL and reduced to > 95% of this value by week 4).
SECONDARY OBJECTIVES:
I. To assess 2-year progression free survival and toxicity in the reduced dose chemo-radiation arm.
II. To determine acute and late toxicity as measured by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0).
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
- •Pathologically confirmed diagnosis of squamous cell carcinoma of the oropharynx (unknown primary, base of tongue, tonsil, oropharyngeal walls, soft palate). Cytologic or fine needle aspiration (FNA) confirmation is sufficient if a biopsy of the primary tumor is not feasible
- •P16 positive immunohistochemical staining. FNA may be used as the sole diagnostic tissue. If staining was done at an outside hospital, central review by the Ohio State University (OSU) department of pathology must occur prior to trial enrollment
- •Clinical stage T0, N1-N2, T1-2, N1-N2, T3-T4, N0-2 (American Joint Committee on Cancer [AJCC] 8th edition) including no evidence of distant metastases based on general history, imaging, physical examination, and examination with laryngopharyngoscopy
- •Clinical or radiographic evidence of measurable disease at the primary site or lymph nodes. Simple tonsillectomy or excision of primary without removal of nodal disease is permitted, as is excision of gross nodes but with intact primary site
- •Fludeoxyglucose F-18 (FDG) PET/CT from the base of skull to the mid-thigh is mandatory and patients cannot be enrolled without a pretreatment PET/CT. PET/CT must be completed prior to enrollment
- •Pretreatment tumor tissue modified HPV virus (TTMV-HPV) particles present in plasma cell free DNA value of >= 200 copies/mL at baseline
- •Patients must provide their smoking history prior to enrollment. Patients must have =< 10 pack years of smoking. The number of pack years will be calculated using the following formula: Frequency of smoking (cigarettes/day) x duration of cigarette smoking (years)/20
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Age >= 18
- •Absolute neutrophil count: ≥ 1500/mcL (within 14 days prior to registration)
- •Platelets: >= 100,000/mcL (within 14 days prior to registration)
- •Hemoglobin >= 8.0 g/dL (use of transfusion or other intervention to achieve this is acceptable) (within 14 days prior to registration)
- •Total bilirubin >= 1.5 x institutional upper limit of normal (within 14 days prior to registration)
- •Aspartate transaminase (AST) or alanine transaminase (ALT) >= 3.0 x institutional upper limit of normal (within 14 days prior to registration)
- •Serum creatinine =< 1.5 x institutional upper limit of normal or creatinine clearance >= 50 mL/min (Cockcroft-Gault Formula) (within 14 days prior to registration)
- •Human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible
- •Patients with known positive hepatitis B surface antigen indicating acute or chronic infection would make patient ineligible unless viral load becomes undetectable on suppressive therapy
- •Patients with history of hepatitis C virus must have been treated and cured
- •For women of childbearing potential, negative serum or urine pregnancy test within 14 days of registration
- •Patient or legally authorized representative must provide study specific informed consent prior to study entry
排除标准
- •Recurrent disease
- •Clinical or radiographic evidence of metastatic disease or adenopathy below the clavicles
- •Cancers from an oral cavity site, even if p16 positive
- •Patients with simultaneous primary cancers or separate bilateral primary tumors will be excluded, except for patients with bilateral tonsil cancers
- •Prior invasive malignancy (except non-melanoma skin cancer) unless disease free for a minimum of 3 years
- •Prior systemic chemotherapy or immunotherapy
- •Prior radiotherapy that would result in overlap of radiation fields
- •Severe active co-morbidity defined as: Unstable angina or congestive heart failure requiring hospitalization in the last 6 months. Condition requiring systemic treatment with steroids or immunosuppressive medications within 14 days of registration
- •Patients with active autoimmune disease requiring systemic treatment (disease modifying agents, corticosteroids, or immunosuppressive drugs
- •Patients who are pregnant, nursing, or expected to conceive or father children
- •Patients who are allergic to cisplatin, carboplatin, or paclitaxel
研究组 & 干预措施
Arm I (reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4.
Patients with reduced > 95% of TTMV undergo external beam radiotherapy QD 5 days a week for 5 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 5 weeks. Patients also undergo blood sample collection during screening and throughout the trial.
干预措施: Biospecimen Collection (Procedure)
Arm I (reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4.
Patients with reduced > 95% of TTMV undergo external beam radiotherapy QD 5 days a week for 5 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 5 weeks. Patients also undergo blood sample collection during screening and throughout the trial.
干预措施: Carboplatin (Drug)
Arm I (reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4.
Patients with reduced > 95% of TTMV undergo external beam radiotherapy QD 5 days a week for 5 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 5 weeks. Patients also undergo blood sample collection during screening and throughout the trial.
干预措施: Cisplatin (Drug)
Arm I (reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4.
Patients with reduced > 95% of TTMV undergo external beam radiotherapy QD 5 days a week for 5 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 5 weeks. Patients also undergo blood sample collection during screening and throughout the trial.
干预措施: Computed Tomography (Procedure)
Arm I (reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4.
Patients with reduced > 95% of TTMV undergo external beam radiotherapy QD 5 days a week for 5 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 5 weeks. Patients also undergo blood sample collection during screening and throughout the trial.
干预措施: External Beam Radiation Therapy (Radiation)
Arm I (reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4.
Patients with reduced > 95% of TTMV undergo external beam radiotherapy QD 5 days a week for 5 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 5 weeks. Patients also undergo blood sample collection during screening and throughout the trial.
干预措施: Paclitaxel (Drug)
Arm I (reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4.
Patients with reduced > 95% of TTMV undergo external beam radiotherapy QD 5 days a week for 5 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 5 weeks. Patients also undergo blood sample collection during screening and throughout the trial.
干预措施: Positron Emission Tomography (Procedure)
Arm I (reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4.
Patients with reduced > 95% of TTMV undergo external beam radiotherapy QD 5 days a week for 5 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 5 weeks. Patients also undergo blood sample collection during screening and throughout the trial.
干预措施: Questionnaire Administration (Other)
Arm II (not reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4.
Patients without reduced > 95% of TTMV undergo external beam radiotherapy daily for 5 days a week for 7 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 7 weeks. . Patients also undergo blood sample collection during screening and throughout the trial.
干预措施: Biospecimen Collection (Procedure)
Arm II (not reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4.
Patients without reduced > 95% of TTMV undergo external beam radiotherapy daily for 5 days a week for 7 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 7 weeks. . Patients also undergo blood sample collection during screening and throughout the trial.
干预措施: Carboplatin (Drug)
Arm II (not reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4.
Patients without reduced > 95% of TTMV undergo external beam radiotherapy daily for 5 days a week for 7 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 7 weeks. . Patients also undergo blood sample collection during screening and throughout the trial.
干预措施: Cisplatin (Drug)
Arm II (not reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4.
Patients without reduced > 95% of TTMV undergo external beam radiotherapy daily for 5 days a week for 7 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 7 weeks. . Patients also undergo blood sample collection during screening and throughout the trial.
干预措施: Computed Tomography (Procedure)
Arm II (not reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4.
Patients without reduced > 95% of TTMV undergo external beam radiotherapy daily for 5 days a week for 7 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 7 weeks. . Patients also undergo blood sample collection during screening and throughout the trial.
干预措施: External Beam Radiation Therapy (Radiation)
Arm II (not reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4.
Patients without reduced > 95% of TTMV undergo external beam radiotherapy daily for 5 days a week for 7 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 7 weeks. . Patients also undergo blood sample collection during screening and throughout the trial.
干预措施: Paclitaxel (Drug)
Arm II (not reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4.
Patients without reduced > 95% of TTMV undergo external beam radiotherapy daily for 5 days a week for 7 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 7 weeks. . Patients also undergo blood sample collection during screening and throughout the trial.
干预措施: Positron Emission Tomography (Procedure)
Arm II (not reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4.
Patients without reduced > 95% of TTMV undergo external beam radiotherapy daily for 5 days a week for 7 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 7 weeks. . Patients also undergo blood sample collection during screening and throughout the trial.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Positron emission tomography complete response
时间窗: At 3 months
Will be evaluated using the Hopkins Criteria which predicts Overall Survival (OS) and Progression-free survival (PFS) in patients with HPV positive oropharyngeal cancers. Separate scores are given for the primary tumor, right neck, and left neck. The activity in the internal jugular vein (IJV) is taken as background blood pool for reference. A score of 1 is consistent with a complete metabolic response, a score of 2 is associated with likely complete metabolic response, a score of 3 is likely inflammatory changes, and a score of 4 is considered likely residual tumor. The overall assessment is denoted by the overall score, which is the highest score among the scores for the primary tumor and right and left neck.
次要结局
- Progression free survival(At 2 years)
- Incidence of adverse events(Up to 1 year)
- Quality of life (QOL)(Up to 1 year)
研究者
Dukagjin Blakaj
Principal Investigator
Ohio State University Comprehensive Cancer Center