A Phase II Study of Sorafenib in Patients With Metastatic Renal Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Toxicity of Intrapatient Dose Escalation of Sorafenib Tosylate
研究概览
简要总结
RATIONALE: Sorafenib 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.
PURPOSE: This phase II trial is studying the side effects and how well sorafenib works in treating patients with metastatic or unresectable kidney cancer.
详细描述
OBJECTIVES:
Primary
- Evaluate the safety and toxicity of dose escalating sorafenib tosylate in patients with metastatic or unresectable renal cell carcinoma.
Secondary
- Determine tumor response in these patients.
- Determine time to progression in these patients.
- Determine overall survival of 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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed renal cell carcinoma (RCC)
- •Must have a component of conventional clear cell RCC
- •Predominant clear cell component ≥ 75%
- •Metastatic or unresectable disease (Measurable disease is defined as any lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan or MRI)
- •Measurable or nonmeasurable disease, includes any of the following:
- •Small lesions, longest diameter < 20 mm by conventional techniques or < 10 mm by spiral CT scan
- •Bone lesions
- •Leptomeningeal disease
- •Pleural/pericardial effusion
- •Lymphangitis cutis/pulmonitis
- •Abdominal masses that are not confirmed and followed by imaging techniques
- •Cystic lesions
- •Irradiated lesions, unless progression is documented after radiotherapy
- •Paraffin RCC tissue blocks or unstained slides must be obtained for future chemistry staining of VEGF
- •Karnofsky performance status 70-100%
- •Fertile patients must use effective contraception (hormonal and/or barrier method) during and for 3 months after completion of study treatment
- •Granulocyte count ≥ 1,500/µL
- •Platelet count ≥ 100,000/µL
- •AST/ALT ≤ 2.5 times upper limit of normal (ULN)
- •Alkaline phosphatase ≤ 2.5 times ULN
- •Serum bilirubin ≤ 1.5 times ULN
- •Protein ≤ 1+ by urinalysis
- •Creatinine ≤ 1.5 times ULN
- •At least 4 weeks since prior major surgery and/or radiotherapy and recovered
- •Prior palliative radiotherapy for metastatic lesion(s) allowed provided there is at least one measurable and/or evaluable lesion(s) that has not been irradiated
- •More than 4 weeks since prior and no other concurrent anticancer therapy
- •Concurrent continuation of bisphosphonates allowed for bone metastases prophylaxis
排除标准
- •Patients with true papillary, sarcomatoid features without any clear cell component, chromophobe, oncocytoma, collecting duct tumors, or transitional cell carcinoma are not eligible
- •No evidence of CNS metastases
- •No imaging (MRI or CT scan of the brain) abnormality indicative of CNS metastases within past 42 days
- •Not pregnant or nursing (negative pregnancy test)
- •No ongoing hemoptysis
- •No cerebrovascular accident within the past 12 months
- •No peripheral vascular disease with claudication while walking less than 1 block
- •No history of clinically significant bleeding
- •No deep venous thrombosis or pulmonary embolus within the past year
- •No significant cardiovascular disease, defined as NYHA class II-IV congestive heart failure, angina pectoris requiring nitrate therapy, or myocardial infarction within the past 6 months
- •No uncontrolled hypertension, defined as systolic BP > 160 mm Hg and/or diastolic BP > 90 mm Hg while on medication
- •No preexisting thyroid abnormality whose thyroid function cannot be maintained in the normal range by medication
- •No uncontrolled psychiatric disorder
- •No delayed healing of wounds, ulcers, and/or bone fractures
- •No currently active second malignancy except nonmelanoma skin cancer (patients are not considered to have a 'currently active' malignancy if they have completed anticancer therapy and are considered by their physician to be at less than 30% risk of relapse)
- •No more than one prior systemic therapy for RCC
- •No prior vascular endothelial growth factor receptor agents
- •No concurrent systemic corticosteroid therapy (except replacement therapy for adrenal insufficiency)
- •o Topical and/or inhaled steroids allowed
- •No concurrent full-dose oral or parenteral anticoagulation
- •o Low-dose warfarin (1 mg) for maintenance of catheter patency or daily prophylactic aspirin allowed
- •No concurrent Hypericum perforatum (St. John's wort)
- •No concurrent ketoconazole, itraconazole, ritonavir, rifampin, or products containing grapefruit juice
- •No concurrent hormonal therapy or chemotherapy o Concurrent hormones administered for non-disease related conditions (e.g., insulin for diabetes) allowed
研究组 & 干预措施
Sorafenib
The initial dose of Sorafenib will be administered orally with a dose of 400 mg twice a day, daily. Intrapatient dose escalation will occur as defined in the table below, providing no dose limiting toxicity (Grade 3 or 4) is observed. If grade 3 or 4 toxicity is observed, delay and dose modification will occur as defined in protocol. Once dose level 3 is reached, the patient will remain at that dose as defined in following section.
Dose Level 1 Day 1-28 400 mg b.i.d. Dose Level 2 Day 29-56 600 mg b.i.d. Dose Level 3 Day 57- 800 mg b.i.d.
A treatment cycle will be 4 weeks.
Two 4-week cycles will be administered. At the completion of two cycles (week 8), restaging will occur. Patients will continue on therapy per study protocol.
干预措施: Sorafenib (Drug)
结局指标
主要结局
Toxicity of Intrapatient Dose Escalation of Sorafenib Tosylate
时间窗: Study completion
To evaluate the toxicity of dose escalating sorafenib, an estimation of the percentage of patients who are unable to tolerate those escalated doses will be made. Patients will be dose escalated every 4 weeks until a maximum dose of 800 mg BID is reached.
次要结局
- Response Rate(from the start of the treatment until disease progression/recurrence)