Phase I/II Clinical, Pharmacological, and Biological Study of BAY 43-9006 in Combination With Cetuximab and Irinotecan in Patients With Advanced Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Toxicity spectrum and dose-limiting toxicities of sorafenib in combination with cetuximab and irinotecan as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v 3.0
研究概览
简要总结
This phase I/II trial is studying the side effects and best dose of sorafenib when given together with cetuximab and irinotecan and to see how well they work in treating patients with advanced or metastatic colorectal cancer. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Sorafenib and cetuximab may also stop tumor growth by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan, work in different ways to kill tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with cetuximab and irinotecan may kill more tumor cells
详细描述
OBJECTIVES:
I. Determine the toxicity spectrum and dose-limiting toxic effects of sorafenib when combined with cetuximab and irinotecan in patients with advanced or metastatic colorectal cancer.
II. Determine the recommended phase II dose of sorafenib when combined with cetuximab and irinotecan in these patients.
III. Correlate the clinical activity of this regimen, in terms of radiologic and positron emission tomography (PET) response, with baseline extracellular signal-regulated kinase (ERK) expression as well as Kirsten rat sarcoma (KRAS), BRAF, and other genetic properties of tumors in these patients.
IV. Determine the pharmacokinetics of this regimen in these patients. V. Correlate the pharmacodynamic effects of this regimen with baseline ERK expression as well as KRAS, BRAF, and other genetic properties of tumors in these patients.
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 colorectal cancer (advanced or metastatic disease not amenable to potential curative resection)
- •Archival tumor (blocks and/or slides) must be available for patients who decline tumor biopsies
- •Tumor must be amenable to sequential biopsies for patients willing to undergo tumor biopsy
- •Must have evidence of disease progression after first-line chemotherapy for advanced disease
- •Previously irradiated lesions are not considered measurable disease
- •Measurable disease, defined as >= 1 unidimensionally measurable target lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan
- •No known brain metastases
- •Eastern Cooperative Oncology Group (ECOG) 0-2 OR Karnofsky 60-100%
- •Life expectancy of more than 12 weeks
- •white blood cell count (WBC) >= 3,000/mm^3
- •Bilirubin normal
- •Creatinine normal OR creatinine clearance >= 60 mL/min
- •No hypertension
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •Not pregnant or nursing
- •Able to swallow oral medication
- •Willing to undergo 2 sequential tumor and skin biopsies
- •No ongoing or active infection
- •No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study drugs
- •No psychiatric illness or social situation that would preclude study compliance
- •No other uncontrolled illness
- •No prior cetuximab
- •No concurrent prophylactic filgrastim (G-CSF), sargramostim (GM-CSF) or epoetin alfa
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •No other concurrent chemotherapy
- •More than 4 weeks since prior radiotherapy and recovered
- •No prior sorafenib
- •No other prior therapy targeted against MAPK
- •More than 14 days since prior and no concurrent administration of the following cytochrome P450 3A4 (CYP3A4) inducers:
- •Rifabutin
- •Hypericum perforatum (St. John's wort)
- •Phenytoin
- •Carbamazepine
- •Phenobarbital
- •More than 7 days since prior and no concurrent administration of the following CYP3A4 inhibitors:
- •Amiodarone
- •Clarithromycin
- •Diltiazem
- •Erythromycin
- •Grapefruit juice
- •Indinavir
- •Saquinavir
- •Lopinavir in combination with ritonavir
- •Fosamprenavir
- •Ritonavir
- •Atazanavir
- •Nelfinavir
- •Itraconazole
- 另有 11 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (sorafenib, irinotecan, cetuximab)
Patients will receive sorafenib by mouth once or twice a day and a 1- to 2-hour infusion of cetuximab once a week for 8 weeks. They will also receive a 1½-hour infusion of irinotecan once a week in weeks 3-6. Patients will then receive sorafenib by mouth once or twice a day and a 1- to 2-hour infusion of cetuximab once a week for 6 weeks. They will also receive a 1½-hour infusion of irinotecan once a week in weeks 1-4. Treatment may repeat every 6 weeks for as long as benefit is shown.
干预措施: sorafenib tosylate (Drug)
Treatment (sorafenib, irinotecan, cetuximab)
Patients will receive sorafenib by mouth once or twice a day and a 1- to 2-hour infusion of cetuximab once a week for 8 weeks. They will also receive a 1½-hour infusion of irinotecan once a week in weeks 3-6. Patients will then receive sorafenib by mouth once or twice a day and a 1- to 2-hour infusion of cetuximab once a week for 6 weeks. They will also receive a 1½-hour infusion of irinotecan once a week in weeks 1-4. Treatment may repeat every 6 weeks for as long as benefit is shown.
干预措施: cetuximab (Drug)
Treatment (sorafenib, irinotecan, cetuximab)
Patients will receive sorafenib by mouth once or twice a day and a 1- to 2-hour infusion of cetuximab once a week for 8 weeks. They will also receive a 1½-hour infusion of irinotecan once a week in weeks 3-6. Patients will then receive sorafenib by mouth once or twice a day and a 1- to 2-hour infusion of cetuximab once a week for 6 weeks. They will also receive a 1½-hour infusion of irinotecan once a week in weeks 1-4. Treatment may repeat every 6 weeks for as long as benefit is shown.
干预措施: irinotecan hydrochloride (Drug)
结局指标
主要结局
Toxicity spectrum and dose-limiting toxicities of sorafenib in combination with cetuximab and irinotecan as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v 3.0
时间窗: Up to 30 days
Clinical activity of the combination of sorafenib, cetuximab and irinotecan in terms of radiological response
时间窗: Up to 30 days
Pharmacokinetics of sorafenib, cetuximab, and irinotecan when given in combination or when given in combination with cetuximab alone and with cetuximab and irinotecan
时间窗: Up to 30 days
Pharmacodynamics of the combination of irinotecan when given in combination with sorafenib and cetuximab in tumor tissues
时间窗: Up to 30 days
Recommended dose for phase II evaluation of the combination of sorafenib, cetuximab and irinotecan
时间窗: 56 days
次要结局
未报告次要终点