A Phase I Trial of Concurrent Chemoradiation/Chemoreirradiation With Cetuximab (ERBITUX®), Sunitinib, and Accelerated Radiation in Patients With Locally Advanced/High-risk/Recurrent Poor Prognosis Head and Neck Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 36
- 试验地点
- 12
- 主要终点
- Maximum-tolerated dose (MTD) of sunitinib malate
研究概览
简要总结
This phase I trial is studying the side effects and best dose of sunitinib when given together with cetuximab and radiation therapy in treating patients with locally advanced or recurrent squamous cell carcinoma of the head and neck. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. 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 sunitinib together with cetuximab and radiation therapy may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To assess the safety, the maximum tolerated dose, and the dose limiting toxicity of sunitinib malate when administered in combination with cetuximab and radiotherapy in patients with locally advanced, recurrent, or second primary poor prognosis, high-risk squamous cell carcinoma of the head and neck.
SECONDARY OBJECTIVES:
I. To describe the toxicity profile of this regimen. II. To explore the tolerability and feasibility of sunitinib malate when administered in combination with cetuximab and radiotherapy in these patients.
III. To assess the best overall response rate (complete and partial response) after completion of treatment.
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
- •Histologically or cytologically confirmed squamous cell carcinoma of the head and neck, meeting any of the following criteria:
- •Recurrent disease
- •Second primary locoregional recurrence* with no clinically measurable distant disease
- •Poor prognosis non-metastatic head and neck carcinoma (M0)
- •Must have undergone radiotherapy as a component of prior treatment
- •Not a candidate for surgical resection with curative intent
- •Patients with high-risk features at resection or following resection for recurrence are eligible
- •Must have locoregional tumor amenable to radiotherapy or reirradiation with curative intent
- •Entire gross tumor recurrence volume must be able to be treated without exceeding a cumulative spinal cord dose of 50 Gy
- •Unresected tumors must be measurable according to RECIST
- •No known brain metastases
- •ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- •Life expectancy > 12 weeks
- •WBC ≥ 3,000/mm^³
- •ANC > 1,500/mm³
- •Platelet count > 100,000/mm³
- •Total bilirubin < 1.5 times upper limit of normal (ULN)
- •INR and PTT ratio < 1.5
- •AST and ALT ≤ 2.5 times ULN
- •Creatinine normal OR creatinine clearance > 60 mL/min
- •Urine protein no more than trace
- •Hematocrit ≥ 28%
- •Hemoglobin ≥ 9 g/dL
- •QTc < 500 msec
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •The following patients are eligible provided they have New York Heart Association class II cardiac function on baseline ECHO and MUGA:
- •Asymptomatic on treatment
- •Prior anthracycline exposure
- •Prior central thoracic radiotherapy included the heart in the radiotherapy port
- •No clinical evidence of active infection of any type, including hepatitis B or C virus
- •Infections controlled with therapy are allowed
- •Patients with hepatitis B or C on antiviral therapy with no detectable virus are allowed
- •No immune deficiency and/or HIV positivity
- •No history of allergic reactions attributed to compounds of similar chemical or biological composition to sunitinib malate
- •No gastrointestinal tract disease or condition, including any of the following, that impairs ability to retain sunitinib tablets:
- •Inability to take oral medication or a requirement for IV alimentation
- •Prior surgical procedures affecting absorption
- •Active peptic ulcer disease
- •None of the following conditions allowed:
- •Serious or nonhealing wound, ulcer, or bone fracture
- •Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
- •No significant concurrent medical or psychiatric illness which, in the opinion of the investigator, would interfere with the patient's ability to participate in the trial
- •No active carotid artery involvement
- •No history of documented thrombosis (pulmonary embolism within the past 12 months or deep vein thrombosis [DVT] within the past 6 months), known coagulopathies or thrombophilia, or evidence of DVT/thromboembolic event
- •No history of the following cardiovascular conditions :
- •Myocardial infarction within the past 12 months
- •Cardiac arrhythmia or serious ventricular arrhythmia (ventricular fibrillation or ventricular tachycardia ≥ 3 beats in a row) within the past 12 months
- •Stable/unstable angina within the past 12 months
- 另有 45 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (enzyme inhibitor and monoclonal antibody therapy)
Patients receive sunitinib malate orally or by percutaneous gastrostomy tube once daily, cetuximab IV over 60-120 minutes once weekly, and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 7-9 weeks in the absence of disease progression or unacceptable toxicity. Patients with persistent disease undergo surgical resection.
干预措施: sunitinib malate (Drug)
Treatment (enzyme inhibitor and monoclonal antibody therapy)
Patients receive sunitinib malate orally or by percutaneous gastrostomy tube once daily, cetuximab IV over 60-120 minutes once weekly, and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 7-9 weeks in the absence of disease progression or unacceptable toxicity. Patients with persistent disease undergo surgical resection.
干预措施: pharmacological study (Other)
Treatment (enzyme inhibitor and monoclonal antibody therapy)
Patients receive sunitinib malate orally or by percutaneous gastrostomy tube once daily, cetuximab IV over 60-120 minutes once weekly, and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 7-9 weeks in the absence of disease progression or unacceptable toxicity. Patients with persistent disease undergo surgical resection.
干预措施: 3-dimensional conformal radiation therapy (Radiation)
Treatment (enzyme inhibitor and monoclonal antibody therapy)
Patients receive sunitinib malate orally or by percutaneous gastrostomy tube once daily, cetuximab IV over 60-120 minutes once weekly, and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 7-9 weeks in the absence of disease progression or unacceptable toxicity. Patients with persistent disease undergo surgical resection.
干预措施: cetuximab (Biological)
结局指标
主要结局
Maximum-tolerated dose (MTD) of sunitinib malate
时间窗: Up to 7-9 weeks
MTD is defined as the dose level immediately below the non-tolerated dose. The study will utilize a standard "3+3" design to determine the MTD. Dose limiting toxicities (DLTs) used for determining escalation of dose will be those occurring within the period of radiotherapy. Toxicity will be summarized by type and severity using the National Cancer Institute (NCI) Common Terminology Criteria.
次要结局
- Pharmacokinetics of sunitinib malate delivered by percutaneous gastrostomy tube(Prior to and up to 24 hours after the start of sunitinib malate)
- Time to progression(From the date of registration to the date of progressive disease or death from any cause)
- Disease control rates(Up to 6 years)
- Locoregional recurrence rates(At 3 years)
- Overall survival time(From the date of registration to the date of death or date of last patient contact if censored)
- Locoregional control rates(Up to 6 years)
- Objective tumor response rates(From the start of the treatment to up to 6 years)