A Phase 2 Study of GW786034 (Pazopanib) in Asian Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 3
- 主要终点
- Clinical Benefit Rate
研究概览
简要总结
This phase II trial studies the side effects and how well pazopanib hydrochloride works in treating patients with stage IV or recurrent nasopharyngeal cancer. Pazopanib hydrochloride 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 the efficacy of pazopanib hydrochloride in patients with stage IV or recurrent nasopharyngeal carcinoma.
II. Determine the progression-free survival of patients treated with this drug. III. Determine the toxicity of this drug in these patients. IV. Determine the effect of this drug on angiogenesis inhibition using dynamic contrast-enhanced computed tomography (CT) scan.
V. Determine the pharmacokinetic profile of this drug in these patients. VI. Correlate the effect of this drug on angiogenesis inhibition with the clinical benefit rate and pharmacokinetics.
OUTLINE:
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 nasopharyngeal carcinoma, meeting the following criteria:
- •World Health Organization (WHO) type II-III disease
- •Stage IV or recurrent disease
- •Must have failed at least 1 prior line of chemotherapy for metastatic or recurrent disease
- •Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan
- •No known brain metastases
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 or Karnofsky PS 70-100%
- •Life expectancy > 3 months
- •WBC >= 3,000/mm³
- •Absolute neutrophil count >= 1,500/mm³
- •Platelet count >= 100,000/mm³
- •Bilirubin normal
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times upper limit of normal (ULN)
- •Creatinine normal OR creatinine clearance >= 60 mL/min
- •Proteinuria =< 1+ on 2 consecutive dipsticks taken >= 1 week apart
- •Prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time (PTT) =< 1.2 times ULN
- •Systolic blood pressure (BP) =< 140 mm Hg and diastolic BP =< 90 mm Hg
- •Initiation or adjustment of BP medication allowed provided the average of 3 BP readings are < 140/90 mm Hg prior to study entry
- •No history of allergic reaction attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or to other study agents
- •No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
- •No cerebrovascular accident within the past 6 months
- •No history of any of the following diseases within the past 12 weeks:
- •Myocardial infarction
- •Cardiac arrhythmia
- •Admission for unstable angina
- •Cardiac angioplasty or stenting
- •Venous thrombosis
- •No New York Heart Association (NYHA) class III-IV heart failure
- •Patients with a history of NYHA class II heart failure are eligible provided they are asymptomatic on treatment
- •No significant electrocardiogram (ECG) abnormalities, including QTc prolongation (i.e., QTc >= 500 msec)
- •No serious or non-healing wound, ulcer, or bone fracture
- •No condition that would impair the ability to swallow and retain pazopanib hydrochloride, including any of the following:
- •Gastrointestinal tract disease resulting in an inability to take oral medication
- •Requirement for IV alimentation
- •Prior surgical procedures affecting absorption
- •Active peptic ulcer disease
- •No concurrent uncontrolled illness including, but not limited to, the following:
- •Coagulopathy
- •Ongoing or active infection
- •Psychiatric illness or social situation that would preclude study compliance
- •No known allergy to CT contrast agents
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
- •More than 4 weeks since prior radiotherapy
- •At least 4 weeks since prior surgery
- •No prior antiangiogenesis therapy
- •No other concurrent investigational agents
- •No other concurrent anticancer therapy
- 另有 5 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (pazopanib hydrochloride)
Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Pharmacological study will be done on Day 1 and Day 28. Computed tomography will be done at baseline and day 28.
干预措施: pazopanib hydrochloride (Drug)
Treatment (pazopanib hydrochloride)
Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Pharmacological study will be done on Day 1 and Day 28. Computed tomography will be done at baseline and day 28.
干预措施: pharmacological study (Other)
Treatment (pazopanib hydrochloride)
Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Pharmacological study will be done on Day 1 and Day 28. Computed tomography will be done at baseline and day 28.
干预措施: computed tomography (Procedure)
结局指标
主要结局
Clinical Benefit Rate
时间窗: 12 weeks of treatment
Clinical benefit rate (CBR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST ver 1.0) and assessed by CT or MRI. CBR includes 1) Complete response (CR): disappearance of all lesions; 2) partial response (PR): \>=30% decrease in the sum of the longest diameter of target lesions and 3) stable disease (SD): non-PR and non progressive disease.
次要结局
- Pharmacokinetic Study: Percentage of Participants With Trough Concentration at Steady State (Day 28) Above 15 µg/mL(Day 28 of treatment)
- Pharmacokinetic Study: Area Under Curve (AUC) 0-24h/Dose on Day 28(Day 28 of treatment)
- Pharmacokinetic Study: Volume of Distribution (Vd/F/Dose) on Day 1(Day 1 of treatment)
- Response Rate (PR)(12 weeks of treatment)
- Progression-free Survival(From the date of enrollment to the date of first documented progression or death, whichever occurs first, or to the date when the patient was last known to be alive, up to 3 years.)
- Overall Survival(From date of enrollment to the study to the date of death from any cause or to the date when the patient was last known to be alive, up to 3 years.)
- Toxicity Profile: Percentage of Participants With Significant (Grade 3/4) Related Adverse Event (AE)(From the time of first treatment with pazopanib hydrochloride to up to 30days after completion of treatment)
- Pharmacodynamic Study: Tumor Blood Flow at Baseline(Pretreatment)
- Pharmacodynamic Study: Tumor Blood Flow on Day 28(28 days post treatment)
- Pharmacokinetic Study: Volume of Distribution at Steady State (Vss/F/Dose) on Day 28(Day 28 of treatment)
- Pharmacokinetic Study: AUC0-24h/Dose on Day 1(Day 1 of treatment)