IIT2019-20-Zumsteg-HPVOPC: Phase II Trial of De-Intensified Post-operative Chemoradiation Following Robotic Surgery for HPV-positive Oropharyngeal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 4
- 主要终点
- 2-Year Progression-Free Survival (PFS)
研究概览
简要总结
This study will enroll patients with HPV-associated oropharyngeal cancer, undergoing resection of all gross visible disease at the primary site and in the lymph nodes. A total of 40 patients who have had or will require surgery to remove cancer cells prior to starting chemoradiation may be enrolled. All eligible patients will receive de-intensified cisplatin-based chemoradiation, with high-risk patients receiving a higher dose and longer treatment period than other patients on the study. The study will assess whether a de-intensified version of standard chemoradiation treatment will be just as effective in treating HPV-associated oropharyngeal cancer while causing less side effects than standard dosing.
详细描述
This is a single arm phase II study that will enroll patients with HPV-associated oropharyngeal cancer, undergoing resection through trans-oral robotic surgery (TORS) of all gross visible disease at the primary site and in the lymph nodes. A total of 36 patients at Cedars-Sinai Medical Center and its affiliates (Tower Hematology-Oncology, Torrance Memorial Physician Network) who have had or will require surgery to remove cancer cells prior to starting chemoradiation may be enrolled. All eligible patients will receive de-intensified cisplatin-based chemoradiation, with high-risk patients receiving a higher dose and longer treatment period than other patients on the study. The treatment period will last 3 to 5 weeks depending on whether the patient is considered high-risk or not. The study will assess whether a de-intensified version of standard chemoradiation treatment will be just as effective in treating HPV-associated oropharyngeal cancer while causing less side effects than standard dosing.
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
- •AJCC 8th edition T0-3N0-2 p16-positive oropharyngeal (tonsil, base of tongue, glossotonsillar sulcus, soft palate, oropharyngeal wall) squamous cell carcinoma or squamous cell carcinoma of unknown primary involving the cervical lymph nodes. Cytologic diagnosis from a cervical lymph node is sufficient for diagnosis in the presence of clinical evidence of a primary tumor in the oropharynx.
- •For patients with pT0 tumors (unknown primary), there must be at least one metastatic lymph node present in cervical level II.
- •p16 should be strongly and diffusely positive in the nuclear and cytoplasmic component in greater than 70% of the tumor cells.
- •Have undergone or will undergo gross total resection of all known disease in the head and neck via transoral robotic surgery. For patients with unknown primary tumors, a minimum of an ipsilateral tonsillectomy and base of tongue resection is required.
- •Have undergone or will undergo neck dissection.
- •Have at least one of the following after surgery:
- •Pathologic stage T3
- •2 or more positive lymph nodes
- •At least one lymph node >3cm
- •Lymphovascular invasion
- •Perineural invasion
- •Extranodal extension
- •Close/positive margins: Close margins are considered <3mm from the peripheral margins and <1mm from the deep margin on the en bloc specimen, unless the area of close margin is re-resected and without carcinoma.
- •Age ≥ 18 years old
- •ECOG performance status 0 or 1 within 56 days of start of chemoradiation.
- •Women of childbearing potential require a negative serum or urine pregnancy test within 28 days prior to start of chemoradiation.
- •Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
- •Adequate hematologic and renal function within 30 days of start of chemoradiation, defined as:
- •Hemoglobin ≥ 9.0 g/dL
- •Platelets ≥ 100, 000 cells/mm3
- •ANC ≥ 1.5 X 109/L
- •Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- •Aspartate aminotransferase/alanine aminotransferase ≤ 3.0 x upper limit of normal (ULN)
- •Serum creatinine ≤1.5 x upper limit of normal (ULN) OR a calculated creatinine clearance ≥60 mL/min
排除标准
- •AJCC 8th edition pT4 or cN3 disease.
- •Radiologic or clinical evidence of distant metastasis.
- •Recurrent disease.
- •Inability to achieve gross total resection at time of surgery.
- •Greater than 56 days (8 weeks) after surgical resection of the primary site.
- •Prior radiation to the head and neck > 30 Gy.
- •Prior active invasive (not in situ) malignancy within the prior 2 years, excluding cutaneous basal cell or squamous cell carcinoma, low or intermediate risk prostate cancer, papillary thyroid cancer, AJCC 8th edition stage I-II breast cancer, or low grade non-Hodgkin lymphoma
- •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
- •Hepatic insufficiency resulting in clinical jaundice and/or known coagulation defects
- •Uncontrolled Acquired Immune Deficiency Syndrome (AIDS), defined as a CD4 count < 200 at screening or an AIDS-defining opportunistic infection within the last 6 months.
- •Moderate to severe hearing loss.
- •Active connective tissue disease (e.g. systemic lupus erythematous, scleroderma) requiring immunosuppression.
- •Pregnant or breast-feeding women.
- •Prior allergic reaction to cisplatin.
- •Live vaccines within 30 days prior to the first dose of chemoradiation. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral vaccine). Season influenza vaccines for injection are generally killed virus vaccines and are allowed; however intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines and are not allowed.
研究组 & 干预措施
De-intensified Cisplatin-based Chemoradiation
This is a non-randomized study, with all patients undergoing de-intensified post-operative cisplatin-based chemoradiation. Dosage level and duration of administration will be determined by whether the patient is high risk or not as assessed by the treating investigator.
干预措施: Cisplatin Chemotherapy (Drug)
De-intensified Cisplatin-based Chemoradiation
This is a non-randomized study, with all patients undergoing de-intensified post-operative cisplatin-based chemoradiation. Dosage level and duration of administration will be determined by whether the patient is high risk or not as assessed by the treating investigator.
干预措施: Cisplatin-based Radiation Therapy (Radiation)
结局指标
主要结局
2-Year Progression-Free Survival (PFS)
时间窗: 2 years
Proportion of patients alive and without evidence of local, regional, or distant recurrence at 2 years from study enrollment.
次要结局
- Regional Control(2 years)
- Mean change in patient-reported outcomes using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30)(2 years)
- Mean change in patient-reported outcomes using University of Michigan Xerostomia-Related Quality of Life Scale (XeQoLS)(2 years)
- Overall Survival (OS)(2 years)
- Local Control(2 years)
- Cause-specific Survival(2 years)
- Progression-free survival (PFS) in high-risk and intermediate risk patient subgroups(2 years)
- Locoregional Control(2 years)
- Distant Control(2 years)
- Mean change in patient-reported outcomes using Hearing Handicap Inventory for Adults (HHIA-S)(2 years)
- Mean change in patient-reported outcomes using Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(2 years)
- Mean change in patient-reported outcomes using 5-level version of the EuroQol five dimensional instrument EQ-5D-5L(2 years)
- Mean change in patient-reported outcomes using the MD Anderson Dysphagia Inventory (MDADI)(2 years)
研究者
Zachary Zumsteg
Assistant Professor
Cedars-Sinai Medical Center