A Groupwide Randomized Phase II Window Study of Two Different Schedules of Irinotecan in Combination With Vincristine And Pilot Assessment of Safety and Efficacy of Tirapazamine Combined With Multiagent Chemotherapy for First Relapse or Progressive Disease in Rhabdomyosarcoma and Related Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Response at week 6 of investigational window therapy (unfavorable risk patients)
研究概览
简要总结
Randomized phase II trial to compare the effectiveness of different combination chemotherapy regimens in treating children who have rhabdomyosarcoma. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells
详细描述
OBJECTIVES:
I. Compare response rate in children with relapsed or progressive rhabdomyosarcoma, undifferentiated sarcoma, or ectomesenchymoma treated with 2 different schedules of irinotecan and vincristine in an upfront phase II window.
II. Determine the progression-free and overall survival of patients treated with multiagent chemotherapy.
III. Determine the toxic effects of tirapazamine, doxorubicin, and cyclophosphamide in these patients.
IV. Determine the toxic effects of irinotecan and vincristine in these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed rhabdomyosarcoma, undifferentiated sarcoma, or ectomesenchymoma
- •First relapse or first occurrence of disease progression
- •Unfavorable-risk patients eligible for study window therapy with irinotecan and vincristine meeting the following criteria:
- •Unfavorable risk defined by any of the following:
- •Embryonal histology with stage I or group I at initial diagnosis with distant recurrence or with local or regional recurrence after prior cyclophosphamide
- •Embryonal histology with initial stage II, III, or IV or group II, III, or IV with any relapse pattern
- •Alveolar histology with any stage or group at initial diagnosis
- •At least unidimensionally measurable disease
- •No prior irinotecan
- •Bone marrow must not be only site of relapse
- •Unfavorable-risk patients ineligible for study window therapy with irinotecan meeting the following criteria:
- •Either no measurable disease OR patient received prior irinotecan
- •Bone marrow as only site of relapse allowed
- •Favorable-risk patients meeting the following criteria:
- •Initial botryoid histology (any stage, any group, or any pattern of relapse)
- •Embryonal histology if either stage I or group I (with either local or regional recurrence)
- •No prior cyclophosphamide
- •No CNS metastases
- •Performance status - ECOG 0-2
- •Performance status - Zubrod 0-2
- •At least 2 months
- •Absolute neutrophil count at least 750/mm^3
- •Platelet count at least 75,000/mm^3 (transfusion independent)
- •Hemoglobin at least 10.0 g/dL (red blood cell transfusion allowed)
- •Bilirubin no greater than 1.5 times normal
- •SGPT less than 2.5 times normal
- •Creatinine no greater than 1.5 times normal
- •Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
- •Shortening fraction at least 27% by echocardiogram
- •Ejection fraction at least 50% by MUGA
- •No prior ischemic heart disease
- •Seizure disorder allowed if well controlled by anticonvulsants
- •No CNS toxicity greater than grade 2
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No prior myeloablative therapy with stem cell transplantation
- •At least 1 week since prior antineoplastic biologic agent
- •At least 1 week since prior growth factor(s)
- •Recovered from prior immunotherapy
- •No concurrent immunomodulating agents
- •See Disease Characteristics
- •See Biologic therapy
- •No more than 1 prior chemotherapy regimen
- •No prior doxorubicin or daunorubicin
- •At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
- •No other concurrent anticancer chemotherapy
- •Concurrent corticosteroid therapy allowed
- •At least 2 weeks since prior small-port radiotherapy.
- •At least 6 months since prior radiotherapy to 50% or more of pelvis
- 另有 4 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: vincristine sulfate (Drug)
Arm I
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: irinotecan hydrochloride (Drug)
Arm I
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: cyclophosphamide (Drug)
Arm I
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: doxorubicin hydrochloride (Drug)
Arm I
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: ifosfamide (Drug)
Arm I
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: etoposide (Drug)
Arm I
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: tirapazamine (Drug)
Arm I
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: filgrastim (Biological)
Arm I
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: sargramostim (Biological)
Arm I
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Arm I
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacogenomic studies (Other)
Arm I
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Arm II
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: vincristine sulfate (Drug)
Arm II
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: irinotecan hydrochloride (Drug)
Arm II
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: cyclophosphamide (Drug)
Arm II
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: doxorubicin hydrochloride (Drug)
Arm II
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: ifosfamide (Drug)
Arm II
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: etoposide (Drug)
Arm II
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: tirapazamine (Drug)
Arm II
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: filgrastim (Biological)
Arm II
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: sargramostim (Biological)
Arm II
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Arm II
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacogenomic studies (Other)
Arm II
Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Response at week 6 of investigational window therapy (unfavorable risk patients)
时间窗: At week 6
Incidence of DLT when tirapazamine is given in combination with cyclophosphamide and doxorubicin, graded according to the NCI CTC v 2.0
时间窗: Up to 6 years
次要结局
- Blood metabolite SN-38 levels (unfavorable risk patients)(Up to 6 years)
- Incidence of toxicities associated with the two administration schedules of irinotecan in combination with vincristine, graded according to the NCI CTC v 2.0 (unfavorable risk patients)(Up to 6 years)
- Progression-free survival(Up to 6 years)
- Survival(Up to 6 years)