A Phase II Trial of Induction Chemotherapy Followed by Cetuximab (Erbitux) With Low Dose vs. Standard Dose IMRT in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 121
- 主要终点
- 24-month Progression-free Survival
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as paclitaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high energy x-rays to kill tumor cells. Giving paclitaxel, cisplatin, and cetuximab together with radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying paclitaxel, cisplatin, and cetuximab to see how well they work when followed by cetuximab and two different doses of intensity-modulated radiation therapy in treating patients with HPV-associated stage III or stage IV cancer of the oropharynx that can be removed by surgery.
详细描述
OBJECTIVES:
Primary
- To evaluate the efficacy of induction therapy comprising paclitaxel, cisplatin, and cetuximab followed by cetuximab in combination with low-dose or standard-dose intensity-modulated radiotherapy, as measured by 2-year progression-free survival (PFS), in patients with human papillomavirus(HPV)-associated resectable stage III-IVB squamous cell carcinoma of the oropharynx.
Secondary
- To assess overall survival.
- To evaluate the objective response, local control, and metastatic rate.
- To evaluate early and late toxicities of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Histologically or cytologically confirmed squamous cell carcinoma of the oropharynx as determined by Hematoxylin and eosin (H&E) staining
- •Newly diagnosed disease
- •Resectable disease OR disease that is expected to become resectable after study treatment
- •Stage III, IVA, or IVB disease as determined by imaging studies (computed tomography (CT) scan with IV contrast or magnetic resonance imaging (MRI) required) and a complete head and neck exam
- •Paraffin-embedded tumor specimen available for central confirmation of HPV-associated disease as determined by H&E staining and in-situ hybridization (ISH) for HPV-16 and immunohistochemistry (IHC) for p16
- •HPV-associated disease is defined as p16 IHC-positive and/or HPV-16 ISH-positive
- •Non-HPV-associated disease is defined as p16 IHC-negative
- •NOTE: If there is limited tumor material, p16 IHC will be performed before HPV-16 ISH
- •Measurable disease of the primary tumor or nodes by clinical and radiographic methods, defined as a lesion that is ≥ 2 cm in at least one dimension by clinical exam AND by radiographic exam with CT scan or MRI (or a lesion that is ≥ 1 cm in at least one dimension if the radiographic exam utilizes spiral CT scan)
- •No primary tumor or nodal metastasis fixed to the carotid artery, skull base, or cervical spine
- •No evidence of distant metastases
- •Eastern Cooperative Oncology Group performance status 0-1
- •Granulocytes ≥ 1,000/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Total serum bilirubin ≤ 1.5 mg/dL
- •Creatinine clearance ≥ 60 mL/min
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No history of another malignancy (except for carcinoma in situ of the cervix and/or nonmelanomatous skin cancer) unless it has been curatively treated and the patient has been disease-free for ≥ 2 years
- •Patients with any of the following within the past 6 months are eligible provided they have been evaluated by a cardiologist and/or neurologist before study entry:
- •New York Heart Association (NYHA) class III-IV congestive heart failure
- •Cerebrovascular accident or transient ischemic attack
- •Unstable angina
- •Myocardial infarction (with or without ST elevation)
排除标准
- •Prior chemotherapy
- •Prior radiotherapy above the clavicles
- •Prior surgery with curative intent for this disease (complete head and neck exam with biopsy allowed)
- •Prior therapy specifically and directly targeting the EGFR pathway
- •Prior severe infusion reaction to a monoclonal antibody
- •Uncontrolled diabetes, uncontrolled infection despite antibiotics, or uncontrolled hypertension within the past 30 days
- •Concurrent illness likely to interfere with study therapy or to prevent surgical resection
- •Pregnant or nursing
研究组 & 干预措施
Group 1
After induction therapy with Paclitaxel and Cisplatin, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 5 weeks (27 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 6 weeks.
干预措施: cetuximab (Biological)
Group 1
After induction therapy with Paclitaxel and Cisplatin, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 5 weeks (27 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 6 weeks.
干预措施: intensity-modulated radiation therapy (IMRT) (Radiation)
Group 1
After induction therapy with Paclitaxel and Cisplatin, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 5 weeks (27 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 6 weeks.
干预措施: Paclitaxel (Drug)
Group 1
After induction therapy with Paclitaxel and Cisplatin, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 5 weeks (27 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 6 weeks.
干预措施: Cisplatin (Drug)
Group 2
After induction therapy with Paclitaxel and Cisplatin, patients undergo standard-dose IMRT 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 7 weeks.
干预措施: cetuximab (Biological)
Group 2
After induction therapy with Paclitaxel and Cisplatin, patients undergo standard-dose IMRT 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 7 weeks.
干预措施: intensity-modulated radiation therapy (IMRT) (Radiation)
Group 2
After induction therapy with Paclitaxel and Cisplatin, patients undergo standard-dose IMRT 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 7 weeks.
干预措施: Paclitaxel (Drug)
Group 2
After induction therapy with Paclitaxel and Cisplatin, patients undergo standard-dose IMRT 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 7 weeks.
干预措施: Cisplatin (Drug)
结局指标
主要结局
24-month Progression-free Survival
时间窗: assessed within 14 days after delivery of the third cycle of induction therapy, and 8 weeks and 6 months after completion of concurrent therapy, then every 6 months until progression or until 3 years from study entry
24-month progression-free survival is defined as the proportion of patients who were alive and progression-free at 24 months post registration. The primary study population for this endpoint is patients who were confirmed post-induction clinical complete response (CR) at their primary sites and subsequently received 5400 cGy radiation therapy to their primary sites.
次要结局
- 24-months Overall Survival(assessed within 14 days after delivery of the third cycle of induction therapy, and 8 weeks and 6 months after completion of concurrent therapy, then every 6 months until progression or until 3 years from study entry)
- Primary Clinical Response Rate(assessed within 14 days after delivery of the third cycle of induction therapy)