Phase II Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, in Children and Young Adults With Refractory Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Response rate (complete response [CR] and partial response [PR]) according to Response Evaluation Criteria in Solid Tumor (RECIST) and World Health Organization (WHO) criteria
研究概览
简要总结
This phase II trial is studying how well ixabepilone works in treating young patients with refractory solid tumors. Drugs used in chemotherapy, such as ixabepilone, 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. Determine the response rate to ixabepilone in various strata of recurrent solid malignant tumors of childhood and young adulthood, including all of the following: Embryonal or alveolar rhabdomyosarcoma, osteosarcoma, Ewing's sarcoma/peripheral neuroectodermal tumor, synovial sarcoma or malignant peripheral nerve sheath tumor, Wilms' tumor, and neuroblastoma.
II. Determine the time to progression for each tumor stratum. III. Prospectively evaluate the feasibility and utility of automated volumetric tumor measurement in patients with measurable pulmonary metastases, and descriptively compare volumetric measurements to 1-dimensional (RECIST criteria) and 2-dimensional (WHO criteria) measurements.
IV. Define and describe the toxicities of ixabepilone.
OUTLINE: This is a multicenter study. Patients are stratified according to disease (Ewing's sarcoma/ peripheral neuroectodermal tumor vs osteosarcoma vs alveolar or embryonal rhabdomyosarcoma vs Wilms' tumor vs neuroblastoma vs synovial sarcoma/malignant peripheral nerve sheath tumor).
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
- 1 Year 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis (at original diagnosis or recurrence) of 1 of the following:
- •Embryonal or alveolar rhabdomyosarcoma
- •Osteosarcoma*
- •Ewing's sarcoma /peripheral neuroectodermal tumor*
- •Synovial sarcoma or malignant peripheral nerve sheath tumor*
- •Wilms' tumor*
- •Age ≤ 21 years at original diagnosis
- •Neuroblastoma
- •Age ≤ 21 years at original diagnosis
- •Clinically or radiographically measurable or evaluable (by iodine I 123 metaiodobenzoguanine sulfate [^123I-MIBG] or bone scan [evaluable tumors must be positive at ≥ 1 site])
- •If lesion was previously irradiated, a biopsy must be performed ≥ 6 weeks after completion of radiotherapy and viable neuroblastoma must be demonstrated
- •No elevated urinary catecholamines and/or bone marrow evidence of tumor with measurable disease clinically or by imaging modalities (CT scan, MRI, ^123I-MIBG, or bone scan)
- •Refractory or recurrent disease with no known curative treatment options
- •ECOG performance status (PS) 0-2 OR Karnofsky PS 50-100% (patients > 16 years of age) OR Lansky PS 50-100% (patients ≤ 16 years)
- •Life expectancy ≥ 8 weeks
- •No evidence of active graft-versus-host disease
- •Absolute neutrophil count ≥ 1,500/mm³ (no growth factors)
- •Platelet count ≥ 75,000/mm³ (transfusion independent)
- •Not pregnant or nursing
- •Fertile patients must agree to use effective contraception
- •Negative pregnancy test
- •Hemoglobin ≥ 8 g/dL (may receive RBC transfusions)
- •Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •ALT ≤ 2.5 times ULN
- •No clinically significant unrelated systemic illness that would preclude study treatment, including any of the following:
- •Serious infections
- •Hepatic, renal, or other organ dysfunction
- •CNS toxicity ≤ grade 2
- •No pre-existing sensory or motor neuropathy ≥ grade 2
- •Seizure disorder allowed provided it is well controlled by anticonvulsants
- •No known prior severe hypersensitivity reaction to agents containing Cremophor EL®
- •Fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy
- •More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks if prior nitrosourea)
- •At least 7 days since prior biologic agents
- •At least 2 weeks since prior local palliative (small-port) radiotherapy
- •At least 6 months since prior craniospinal radiotherapy OR radiotherapy to ≥ 50% of the pelvis
- •At least 6 weeks since other prior substantial bone marrow radiotherapy
- •At least 4 months since prior allogeneic stem cell transplant (SCT)
- •At least 2 months since prior autologous SCT
- •No prior taxane (paclitaxel, docetaxel) therapy
- •More than 1 week since prior growth factor use (except epoetin alfa)
- •More than 1 week since prior and no concurrent strong inhibitors ofCYP3A4, including any of the following:
- •Clarithromycin
- •Troleandomycin
- •Erythromycin
- •Ketoconazole
- •Itraconazole
- •Fluconazole (doses > 3mg/kg/day)
- •Voriconazole
- 另有 19 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (ixabepilone)
Patients receive ixabepilone IV over 1 hour on days 1-5. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.
干预措施: ixabepilone (Drug)
结局指标
主要结局
Response rate (complete response [CR] and partial response [PR]) according to Response Evaluation Criteria in Solid Tumor (RECIST) and World Health Organization (WHO) criteria
时间窗: Up to 5 years
Response rates will be calculated as the percent of patients whose best response is a CR or PR, and the fraction of responses obtained will have a 95% confidence interval, which takes into consideration the two-stage nature of the design.
Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
时间窗: Up to 5 years
Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.
Time to progression
时间窗: From enrollment until disease progression, death because of treatment complications, resection of measurable tumor or last patient follow-up whichever is first, assessed up to 5 years
Estimated using the product-limit method of Kaplan and Meier.
Progression-free survival (PFS)
时间窗: At 6 months
The probability of PFS at 6 months will be summarized.
次要结局
未报告次要终点