A Phase II Trial of GW786034 (Pazopanib) in Patients With Recurrent Glioblastoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 9
- 主要终点
- 6 Months Progression-free Survival
研究概览
简要总结
This phase II trial is studying the side effects and how well pazopanib works in treating patients with recurrent glioblastoma. Pazopanib 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 therapeutic efficacy of pazopanib hydrochloride, as measured by 6-month progression-free survival (PFS), in patients with recurrent glioblastoma.
II. Determine the safety profile of this drug in these patients.
SECONDARY OBJECTIVES:
I. Determine the efficacy of this drug, as measured by radiographic response, time to progression, and overall survival, 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 confirmed glioblastoma multiforme, including gliosarcoma
- •Recurrent disease
- •Must have unequivocal radiographic evidence of tumor progression by MRI, as defined by any of the following:
- •25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline
- •Clear worsening of any evaluable disease
- •Appearance of any new lesions or site
- •Clear clinical worsening
- •Must have failed prior radiotherapy that was completed ≥ 42 days ago
- •Patients who received prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease, rather than radiation necrosis, based on positron emission tomography (PET) scan, thallium scanning, magnetic resonance spectroscopy, or surgical documentation of disease
- •Treatment for no more than 2 prior relapses allowed
- •Relapse is defined as progression following initial therapy (i.e., radiotherapy with or without chemotherapy, if that was used as initial therapy; therefore no more than 3 prior therapies [initial therapy and therapy for 2 relapses] allowed)
- •If the patient had a surgical resection for relapsed disease and no anticancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered as 1 relapse
- •For patients who had prior therapy for a low-grade glioma, the surgical diagnosis of a glioblastoma multiforme will be considered the first relapse
- •Karnofsky performance status 60-100%
- •Life expectancy > 8 weeks
- •WBC ≥ 3,000/mm^3
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Hemoglobin ≥ 10 g/dL (may be reached by transfusion)
- •Platelet count ≥ 100,000/mm^3
- •PT/INR/PTT ≤ 1.2 times upper limit of normal (ULN)
- •SGOT < 2.5 times ULN
- •Bilirubin < 2.5 times ULN
- •Creatinine < 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
- •Urine protein:creatinine ratio > 1 OR urine protein < 1,000 mg by 24-hour urine collection OR proteinuria < 1+
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective double-barrier contraception during study therapy OR practice abstinence from sexual intercourse for 14 days prior to, during, and for ≥ 21 days after study therapy
- •Systolic blood pressure (BP) ≤ 140 mm Hg and diastolic BP ≤ 90 mm Hg
- •Prior initiation or adjustment of BP medication allowed provided the average of 3 BP readings is ≤ 140/90 mm Hg
- •No uncontrolled significant medical illnesses that would preclude study therapy
- •No other conditions, including any of the following:
- •Serious or nonhealing wound, ulcer, or bone fracture
- •Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
- •Cerebrovascular accident (CVA) within the past 6 months
- •Myocardial infarction, cardiac arrhythmia, admission for unstable angina, cardiac angioplasty, or stenting within the past 84 days
- •Venous thrombosis within the past 84 days
- •New York Heart Association (NYHA) class III or IV heart failure
- •Asymptomatic NYHA class II heart failure while on treatment allowed
- •No other cancer except for nonmelanoma skin cancer or carcinoma in situ of the cervix unless in complete remission and off of all therapy for that disease for ≥ 3 years
- •No disease that would obscure toxicity or dangerously alter drug metabolism
- •No history of allergic reactions attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or other agents
- •No QTc prolongation (i.e., QTc interval ≥ 500 msecs) or other significant ECG abnormalities
- •No condition that impairs 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
- •See Disease Characteristics
- •Recovered from prior therapy
- •At least 28 days since prior resection of recurrent or progressive tumor and recovered
- 另有 24 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (pazopanib hydrochloride)
Patients receive oral pazopanib hydrochloride daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Other: laboratory biomarker analysis
干预措施: pazopanib hydrochloride (Drug)
Treatment (pazopanib hydrochloride)
Patients receive oral pazopanib hydrochloride daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Other: laboratory biomarker analysis
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
6 Months Progression-free Survival
时间窗: 6 months
Calculated from study registration till 6month time point. Progression defined by Macdonald criteria Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration
Number of Participants Discontinuing Treatment Due to Toxicity
时间窗: 2 years
Use NCI Common toxicity Criteria Adverse Event Version 3.0 to grade toxicities. Any patient who received at least one dose of pazopanib was evaluable for toxicity. Calculated the number of participants who had an event that was related to pazopanib that caused the patient to stop treatment due to this event.
次要结局
- Most Common Toxicities Experienced After at Least One Dose of Pazopanib(Up to 2 years)
- Overall Radiographic Response (ORR) Rate(2 years)
- Best Radiographic Response(3 years)
- Overall Survival(From date of registration to date of death due to any cause, assessed up to 2 years)
- Time to Progression or Progression Free Survival(1 year)