Pharmacodynamic Study of Sunitinib Malate in Patients With Renal Cell Cancer and Other Advanced Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Objective response
研究概览
简要总结
This phase I trial is studying the side effects and best way to give sunitinib malate in treating patients with unresectable or metastatic kidney cancer or other advanced solid tumors. Sunitinib malate may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. Determine the pharmacodynamic change using functional imaging (3'-deoxy-3'-[18F] fluorothymidine [FLT]-positron emission tomography [PET]/computed tomography [CT] scans) in patients with unresectable or metastatic clear cell renal cell carcinoma or other advanced solid malignancies treated with two different schedules of sunitinib malate.
II. Evaluate the objective response in patients treated with this drug.
SECONDARY OBJECTIVES:
I. Measure the change in plasma vascular endothelial growth factor (VEGF) levels and plasma hypoxia-inducible factor (HIF)1-alpha levels as a potential mechanism for vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) failure and rapid tumor growth following VEGFR TKI withdrawal in these patients.
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
- •Patients must have histologically or cytologically confirmed renal cell cancer; or other solid malignancy (excluding lymphoma) that is metastatic or unresectable and for which no standard curative therapy exists
- •For the renal cell cancer subset, a component of clear cell histology is required
- •Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques or >= 10 mm by spiral CT scan
- •Life expectancy > 12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Leukocytes >= 3,000/mm^3
- •Absolute neutrophil count (ANC) >= 1,500/mm^3
- •Platelet count >= 100,000/mm^3
- •Hemoglobin >= 9 g/dL
- •Serum calcium =< 12.0 mg/dL
- •Total bilirubin normal
- •Aspartate aminotransferase (AST) (serum glutamic oxalo-acetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times upper limit of normal (ULN), unless subjects have liver metastases, in which case both AST and ALT must be =< 5 x ULN
- •Creatinine =< 2 times ULN OR creatinine clearance >= 40 mL/min for patients with creatinine levels above 2 x institutional normal
- •All patients need to be willing to undergo planned pharmacodynamic assessments, including serial PET imaging, plasma markers, and pharmacokinetic sampling
- •Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Patients who have had chemotherapy, radiotherapy, experimental therapy or major surgery within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered (to grade < 1 or baseline) from clinically significant adverse events due to agents administered more than 4 weeks earlier (alopecia and fatigue excluded); clinical significance to be determined by investigator
- •Patients may not be receiving any other investigational agents
- •No prior treatment with an anti-VEGF agent allowed
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate
- •Patients with QTc prolongation (defined as a QTc interval greater than 500 msec) or other significant electrocardiogram (ECG) abnormalities (per investigator discretion) are excluded
- •Patients with poorly controlled hypertension (systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher) are ineligible
- •Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain sunitinib tablets are excluded
- •Patients with any of the following conditions are excluded:
- •Serious or nonhealing wound, ulcer, or bone fracture
- •Abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within the past 28 days
- •Cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry
- •History of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within the past 12 months
- •History of pulmonary embolism within the past 12 months
- •Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
- •Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible; patients with a history of hypothyroidism are eligible provided they are currently euthyroid
- •Patients with known brain metastases
- •Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infections or psychiatric illness/social situations that would limit compliance with study requirements are ineligible
- •Pregnant or breastfeeding
- •No concurrent therapeutic doses of coumarin-derivative anticoagulants, such as warfarin; Concurrent doses =< 2 mg/day allowed for prophylaxis of thrombosis, Concurrent low molecular weight heparin allowed provided prothrombin time (PT) international normalized ratio ( INR) =< 1.5
- •No concurrent agents with proarrhythmic potential (terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, and flecainide acetate)
- •Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
研究组 & 干预措施
Schedule A
Patients receive sunitinib malate PO QD in weeks 1-4. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Computed Tomography (Other)
Schedule A
Patients receive sunitinib malate PO QD in weeks 1-4. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Fluorothymidine F-18 (Other)
Schedule A
Patients receive sunitinib malate PO QD in weeks 1-4. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Schedule A
Patients receive sunitinib malate PO QD in weeks 1-4. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
Schedule A
Patients receive sunitinib malate PO QD in weeks 1-4. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Positron Emission Tomography (Other)
Schedule A
Patients receive sunitinib malate PO QD in weeks 1-4. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Sunitinib Malate (Drug)
Schedule B
Patients receive sunitinib malate PO QD in weeks 1, 2, 4, and 5. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Computed Tomography (Other)
Schedule B
Patients receive sunitinib malate PO QD in weeks 1, 2, 4, and 5. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Fluorothymidine F-18 (Other)
Schedule B
Patients receive sunitinib malate PO QD in weeks 1, 2, 4, and 5. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
Schedule B
Patients receive sunitinib malate PO QD in weeks 1, 2, 4, and 5. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Positron Emission Tomography (Other)
Schedule B
Patients receive sunitinib malate PO QD in weeks 1, 2, 4, and 5. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Sunitinib Malate (Drug)
结局指标
主要结局
Objective response
时间窗: Up to 3 years
Standard uptake value as measured by 3'-deoxy-3'-[18F] fluorothymidine (FLT)-PET/CT scans
时间窗: Up to 3 years
Plasma VEGF and HIF1-alpha levels
时间窗: Up to 3 years
次要结局
- Pharmacokinetic parameters (Cmax, Tmax, AUC, T1/2, and CL)(Up to 3 years)