A Dose Escalation Study of Sorafenib (BAY 43-9006, NSC 724772) in Nomotensive Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Changes in BP
研究概览
简要总结
This randomized phase I trial is studying the side effects, such as high blood pressure, and best dose of sorafenib in treating patients with advanced solid tumors. 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.
详细描述
PRIMARY OBJECTIVES:
I. Determine whether increasing the dose of sorafenib tosylate increases the plasma steady-state concentration in patients with advanced solid tumors.
II. Determine whether increasing the dose of this drug affects blood pressure in these patients.
SECONDARY OBJECTIVES:
I. Determine whether the variability in blood pressure elevation is due to pharmacokinetic or pharmacodynamic variability.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed malignant solid tumor
- •Refractory disease for which curative or palliative measures have failed or for which there is no known superior treatment
- •No colorectal cancer or melanoma
- •Measurable OR nonmeasurable disease
- •Normotensive (blood pressure [BP] ≤ 140/90 mm Hg) meeting 1 of the following criteria:
- •No more than 2 attempted measurement sessions for which the documented mean systolic BP is ≤ 140 mm Hg and the diastolic BP is ≤ 90 mm Hg
- •At least 30 attempted measurement sessions for which the documented mean systolic BP is ≤ 135 mm HG and the diastolic BP is ≤ 85 mm Hg
- •Brain metastases allowed provided the following criteria are met:
- •Stable neurologic status for ≥ 2 weeks after completion of definitive local therapy (surgery or radiotherapy)
- •No neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- •ECOG performance status 0-1
- •Life expectancy > 12 weeks
- •Age ≥ 14 years OR weight ≥ 45 kilograms (pediatric patients)
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Hemoglobin ≥ 8.5 g/dL
- •Absolute neutrophil count ≥ 1,500/mm³
- •Platelet count ≥ 100,000/mm³
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST and ALT ≤ 2.5 times ULN (5 times ULN if there is liver involvement)
- •Creatinine ≤ 1.5 times ULN
- •No New York Heart Association class II-IV congestive heart failure
- •No unstable angina (anginal symptoms at rest) or new-onset angina (began within the past 3 months)
- •No myocardial infarction within the past 6 months
- •No ventricular arrhythmias requiring anti-arrhythmic therapy
- •No thrombotic or embolic events, such as symptomatic pulmonary embolus or any cerebrovascular accident (including transient ischemic attacks) within the past 6 months
- •No pulmonary hemorrhage/bleeding event > grade 2 within the past 4 weeks
- •No other hemorrhage/bleeding event > grade 3 within the past 4 weeks
- •No evidence or history of bleeding diathesis or coagulopathy
- •No serious nonhealing wound, ulcer, or bone fracture
- •No ongoing or active infection > grade 2
- •No psychiatric illness or social situation that would limit compliance with study requirements
- •No allergy to sorafenib tosylate or excipients
- •No unstable condition that would jeopardize the safety of the patient and/or her/his compliance with the study
- •No significant traumatic injury within the past 4 weeks
- •No condition that would impair the patient's ability to swallow whole pills or capacity to absorb oral medications
- •No seizure disorder requiring steroids or anticonvulsant therapy
- •No other concurrent illness
- •Recovered from prior therapy
- •Prior vascular endothelial growth factor (VEGF) pathway inhibitor (e.g., bevacizumab, sunitinib malate, axitinib) allowed provided the following criteria are met:
- •The patient's best response as measured by RECIST criteria was not progressive disease
- •If the most recent agent was a small molecule reversible inhibitor (e.g., sunitinib malate, cediranib, or axitinib), the patient must not have taken a dose of the agent within 2 weeks of the baseline blood pressure session and 3 weeks of starting sorafenib tosylate
- •If the most recent agent was bevacizumab or VEGF trap the patient must not have received the most recent dose within 5 weeks of the baseline blood pressure session and 6 weeks of starting sorafenib tosylate AND no grade 3 bleeding, cardiovascular, skin, or thyroid toxicities on one of these previous therapies
- •More than 2 weeks since prior and no concurrent radiotherapy
- •At least 3 weeks since prior and no concurrent chronic epoetin alfa (or congeners)
- •More than 3 weeks since prior immunotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)
- •More than 4 weeks since prior major surgery or open biopsy
- •At least 3 weeks since prior uncharacterized herbal agents or nutritional supplements
- •More than 12 weeks since prior radioimmunotherapy
- 另有 11 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm II (standard-dose enzyme inhibitor therapy)
Patients receive standard-dose oral sorafenib tosylate three times daily on days 15-36.
干预措施: assessment of therapy complications (Procedure)
Arm II (standard-dose enzyme inhibitor therapy)
Patients receive standard-dose oral sorafenib tosylate three times daily on days 15-36.
干预措施: laboratory biomarker analysis (Other)
Arm I (higher-dose enzyme inhibitor therapy)
Patients receive higher-dose oral sorafenib tosylate twice daily on days 15-36.
干预措施: sorafenib tosylate (Drug)
Arm I (higher-dose enzyme inhibitor therapy)
Patients receive higher-dose oral sorafenib tosylate twice daily on days 15-36.
干预措施: pharmacological study (Other)
Arm I (higher-dose enzyme inhibitor therapy)
Patients receive higher-dose oral sorafenib tosylate twice daily on days 15-36.
干预措施: assessment of therapy complications (Procedure)
Arm I (higher-dose enzyme inhibitor therapy)
Patients receive higher-dose oral sorafenib tosylate twice daily on days 15-36.
干预措施: laboratory biomarker analysis (Other)
Arm II (standard-dose enzyme inhibitor therapy)
Patients receive standard-dose oral sorafenib tosylate three times daily on days 15-36.
干预措施: sorafenib tosylate (Drug)
Arm II (standard-dose enzyme inhibitor therapy)
Patients receive standard-dose oral sorafenib tosylate three times daily on days 15-36.
干预措施: pharmacological study (Other)
Arm III (standard-dose enzyme inhibitor therapy)
Patients receive standard-dose oral sorafenib tosylate twice daily on days 15-36. (closed to accrual as of 4/29/2009)
干预措施: sorafenib tosylate (Drug)
Arm III (standard-dose enzyme inhibitor therapy)
Patients receive standard-dose oral sorafenib tosylate twice daily on days 15-36. (closed to accrual as of 4/29/2009)
干预措施: pharmacological study (Other)
Arm III (standard-dose enzyme inhibitor therapy)
Patients receive standard-dose oral sorafenib tosylate twice daily on days 15-36. (closed to accrual as of 4/29/2009)
干预措施: assessment of therapy complications (Procedure)
Arm III (standard-dose enzyme inhibitor therapy)
Patients receive standard-dose oral sorafenib tosylate twice daily on days 15-36. (closed to accrual as of 4/29/2009)
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Changes in BP
时间窗: From baseline to day 21
BP will first be calculated for each subject as BP after 1 week of treatment minus BP before that treatment dose. Then, for each randomized group separately, the BP changes in the two study phases will be compared using paired t-tests.
次要结局
- Toxicity rates in the two high dose groups(Every 2 weeks, assessed up to 1 year)
- Association between steady state trough levels of sorafenib and BP(Days 8 and 22)
- Effect of sorafenib dose/exposure on thyroid function(From baseline up to 50 days)