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临床试验/NCT00436852
NCT00436852已完成2 期

A Phase II Study of ABT-751, an Orally Bioavailable Tubulin Binding Agent, in Children With Relapsed or Refractory Neuroblastoma

Children's Oncology Group12 个研究点 分布在 2 个国家目标入组 92 人开始时间: 2007年1月最近更新:
适应症
干预措施
相关药物

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

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)

Experimental

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)

Experimental

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)

Experimental

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)

Experimental

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.)

研究者

申办方类型
Network
责任方
Sponsor

研究点 (12)

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