A Phase II Study of ABT-751, an Orally Bioavailable Tubulin Binding Agent, in Children With Relapsed or Refractory Neuroblastoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 92
- 试验地点
- 12
- 主要终点
- Median Time to Progression as Assessed by Response Evaluation Criteria in Solid Tumors
研究概览
简要总结
This phase II trial is studying how well ABT-751 works in treating children with neuroblastoma that has relapsed or not responded to previous treatment. Drugs used in chemotherapy, such as ABT-751, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
详细描述
PRIMARY OBJECTIVES:
I. Compare the time to disease progression in children with refractory or relapsed neuroblastoma treated with ABT-751 vs historical controls.
SECONDARY OBJECTIVES:
I. Determine the objective response rate in patients with measurable disease treatment with this drug.
II. Determine whether ABT-751 improves quality of life of these patients. III. Determine the toxicity of ABT-751. IV. Determine the pharmacokinetic profile of ABT-751 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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed neuroblastoma meeting the following criteria:
- •Refractory or relapsed disease
- •No curative treatment option and no additional therapy proven to prolong survival with an acceptable quality of life is available
- •Evidence of disease progression (enlargement of existing measurable tumors or the appearance of new tumors) during prior treatment OR biopsy-proven viable neuroblastoma if stable disease but refractory to prior treatment
- •Previously irradiated soft tissue or bony lesion must meet ≥ 1 of the following criteria:
- •Viable neuroblastoma determined by biopsy ≥ 6 weeks after radiation therapy
- •Growth in the lesion determined by CT scan or MRI
- •Measurable or evaluable disease
- •Measurable disease is defined as ≥ 20 mm in ≥ 1 dimension by MRI, CT scan, or x-ray OR ≥ 10 mm in ≥ 1 dimension by spiral CT scan
- •Evaluable disease is defined as iodine I 123 metaiodobenzylguanidine (^123I MIBG)-positive lesion at ≥ 1 site
- •Must not have measurable disease by CT scan or MRI
- •No elevated urinary catecholamines and/or bone marrow evidence of tumor, without measurable or evaluable disease by imaging modalities (CT scan, MRI, or ^123I MIBG)
- •Karnofsky performance status (PS) 50-100% (> 16 years of age) OR Lansky PS 50-100% (≤ 16 years of age)
- •Life expectancy ≥ 8 weeks
- •Hemoglobin ≥ 7.5 g/dL (transfusions allowed)
- •Absolute neutrophil count > 250/mm³
- •Platelet count > 25,000/mm³ (without platelet transfusion support for ≥ 7 days)
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •ALT < 5 times ULN
- •Creatinine normal for age and gender as follows: OR creatinine clearance or radioisotope glomerular filtration rate ≥ 60 mL/min
- •No greater than 0.4 mg/dL (≤ 5 months)
- •No greater than 0.5 mg/dL (6 months-11 months)
- •No greater than 0.6 mg/dL (1 year-23 months)
- •No greater than 0.8 mg/dL (2 years-5 years)
- •No greater than 1.0 mg/dL (6 years-9 years)
- •No greater than 1.2 mg/dL (10 years-12 years)
- •No greater than 1.4 mg/dL (13 years and over [female])
- •No greater than 1.5 mg/dL (13 years to 15 years [male])
- •No greater than 1.7 mg/dL (16 years and over [male])
- •Shortening fraction ≥ 27% by echocardiogram
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective double-barrier contraception during and for 90 days after completion of study treatment
- •Seizure disorder allowed if controlled and receiving anticonvulsants
- •Neurologic toxicity from prior therapy or tumor involvement ≤ grade 2
- •No evidence of active graft-vs-host disease
- •No allergy to sulfa-containing medications
- •No known HIV positivity
- •No clinically significant unrelated systemic illness (e.g., serious infection) that would limit study compliance
- •Concurrent filgrastim (G-CSF) allowed if medically indicated
- •Recovered from all prior therapy
- •No prior ABT-751
- •More than 2 weeks since prior myelosuppressive chemotherapy
- •More than 7 days since prior anticancer biologic agents (e.g., retinoids)
- •More than 4 weeks since prior palliative radiation therapy (small port) or therapeutic ^123I MIBG
- •More than 6 weeks since prior substantial radiation therapy (> 50% pelvis, craniospinal, or total-body radiation)
- •More than 4 months since prior allogeneic stem cell transplantation (SCT) (2 months for autologous SCT) and recovered
- •Infusion of autologous peripheral blood mononuclear cells without high-dose chemotherapy or preparative regimen is not considered SCT
- •More than 30 days since prior investigational drug therapy
- •More than 30 days since prior immunotherapy (monoclonal antibody therapy or vaccine therapy)
- 另有 5 项未显示
排除标准
- 未提供
研究组 & 干预措施
Measurable disease by CT or MRI scan (ABT-751 chemotherapy)
Patients receive oral ABT-751 (200 mg/m2) once daily on days 1-7. Treatment repeats every 21 days for 52 courses in the absence of disease progression or unacceptable toxicity. Quality-of-life assessment at baseline and prior to each course of treatment. A pharmacological study (pharmacokinetic profile of ABT-751) will be determined.
干预措施: ABT-751 (Drug)
Measurable disease by CT or MRI scan (ABT-751 chemotherapy)
Patients receive oral ABT-751 (200 mg/m2) once daily on days 1-7. Treatment repeats every 21 days for 52 courses in the absence of disease progression or unacceptable toxicity. Quality-of-life assessment at baseline and prior to each course of treatment. A pharmacological study (pharmacokinetic profile of ABT-751) will be determined.
干预措施: quality-of-life assessment (Procedure)
Evaluable by I-MIBG scintigraphy (ABT-751)
Patients receive oral ABT-751 (200 mg/m2) once daily on days 1-7. Treatment repeats every 21 days for 52 courses in the absence of disease progression or unacceptable toxicity. Quality-of-life assessment at baseline and prior to each course of treatment. A pharmacological study (pharmacokinetic profile of ABT-751) will be determined.
干预措施: ABT-751 (Drug)
Evaluable by I-MIBG scintigraphy (ABT-751)
Patients receive oral ABT-751 (200 mg/m2) once daily on days 1-7. Treatment repeats every 21 days for 52 courses in the absence of disease progression or unacceptable toxicity. Quality-of-life assessment at baseline and prior to each course of treatment. A pharmacological study (pharmacokinetic profile of ABT-751) will be determined.
干预措施: quality-of-life assessment (Procedure)
结局指标
主要结局
Median Time to Progression as Assessed by Response Evaluation Criteria in Solid Tumors
时间窗: From time to enrollment to death due to any cause, assessed up to 5.1 years
Median time to progression observed on ABT-751, along with 95% confidence intervals.
1-year Progression-free Survival
时间窗: From the day of enrollment to the date of disease progression/recurrence , or the date of death (all causes of mortality) if disease progression/recurrence is not reached, assessed up to 1 yr. Pts were to be followed for 5 yrs after completion of therapy
PFS probabilities calculated using the Kaplan-Meier method, along 95% confidence intervals, separately for each stratum.
次要结局
- Objective Response Rate(Duration of protocol therapy, up to 3 years)
- Quality of Life Measured by PedsQL™ Generic Core Scale Version 4.0(At baseline)
- Percentage of Participants With Grade 3 or Higher Toxicity(From enrollment until 30 days after the end of protocol therapy)
- Pharmacokinetics of ABT-751: Tmax(After the first dose of ABT-751, at 0.5, 1, 2, 3, 5, 8, 10-12, and 24 hours post-dose.)
- Pharmacokinetics of ABT-751: Cmax(After the first dose of ABT-751, at 0.5, 1, 2, 3, 5, 8, 10-12, and 24 hours post-dose.)
- Pharmacokinetics of ABT-751: AUC(After the first dose of ABT-751, at 0.5, 1, 2, 3, 5, 8, 10-12, and 24 hours post-dose.)