Randomized Study of Vincristine, Dactinomycin and Cyclophosphamide (VAC) Versus VAC Alternating With Vincristine and Irinotecan (VI) for Patients With Intermediate-Risk Rhabdomyosarcoma (RMS)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 481
- 试验地点
- 226
- 主要终点
- Event Free Survival (EFS)
研究概览
简要总结
This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work when given together with radiation therapy in treating patients with newly diagnosed rhabdomyosarcoma. Drugs used in chemotherapy, such as vincristine sulfate, dactinomycin, cyclophosphamide, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective when given together with radiation therapy in treating patients with rhabdomyosarcoma.
详细描述
PRIMARY OBJECTIVES:
I. To compare the early response rates, failure-free survival (FFS), and survival of patients with intermediate-risk rhabdomyosarcoma (RMS) treated with surgery, radiotherapy, and vincristine (vincristine sulfate), dactinomycin and cyclophosphamide (VAC) or VAC alternating with vincristine, irinotecan (irinotecan hydrochloride) (VI).
SECONDARY OBJECTIVES:
I. To compare FFS, local control, and survival of patients with intermediate-risk RMS treated with VAC and early (week 4) radiotherapy vs delayed (week 10) radiotherapy, using data from Intergroup Rhabdomyosarcoma Study (IRS)-IV for historic comparison.
II. To compare the acute and late effects of VAC to VAC alternating with VI, including the toxicity associated with concurrent VI and radiotherapy.
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 49 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with newly diagnosed embryonal RMS, botryoid or spindle cell variants of embryonal RMS, ectomesenchymoma, or alveolar RMS are eligible for this study
- •Enrollment on COG-D9902 to confirm local histologic diagnosis with central pathology review is required for all patients
- •Patients may be enrolled on ARST0531 and start protocol treatment prior to receipt of central pathology review results
- •Patient must have Intermediate-risk RMS defined as:
- •Embryonal, botryoid, or spindle cell RMS, or ectomesenchymoma: stage 2 or 3 and group III OR
- •Alveolar RMS: stage 1-3 and group I-III
- •Staging ipsilateral retroperitoneal lymph node dissection (SIRLND) is required for all patients >= 10 years of age with paratesticular tumors and for patients < 10 years with clinically or radiographically involved lymph nodes (except when extensive lymph node involvement, defined as two or more lymph nodes > 2 cm in dimension, is identified by imaging studies)
- •Regional lymph node sampling or sentinel lymph node procedure is required for histologic evaluation in patients with extremity tumors
- •Clinically or radiographically enlarged nodes should be sampled for histologic evaluation
- •Detection of metastasis by optional FDG PET (not required for study enrollment); FDG PET may detect abnormalities suggestive of metastasis not identified by bone scan, computed tomography (CT), or bone marrow aspiration/biopsy; the prognostic significance of FDG PET-detected abnormalities is not clear; FDG PET-detected abnormalities MUST be confirmed to be metastases by an additional imaging modality (such as magnetic resonance imaging [MRI] or CT) OR pathologic confirmation; unless FDG PET abnormalities are confirmed by another imaging modality or biopsy, FDG PET abnormalities will NOT be considered evidence of metastasis
- •Patients must have a performance status of 0, 1, or 2; the Lansky performance score should be used for patients < 16 years and the Karnofsky performance score for patients >= 16 years
- •Patients who have received prior chemotherapy (excluding steroids) or radiation therapy, except for patients transferring from ARST0331 (low-risk study), are not eligible
- •Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
- •1 month to < 6 months: 0.4 mg/dL
- •6 months to < 1 year: 0.5 mg/dL
- •1 to < 2 years: 0.6 mg/dL
- •2 to < 6 years: 0.8 mgt/dL
- •6 to < 10 years: 1 mg/dL
- •10 to < 13 years: 1.2 mg/dL
- •13 to < 16 years: 1.5 mg/dL (males) or 1.4 mg/dL (females)
- •>= 16 years: 1.7 mg/dL (males) or 1.4 mg/dL (females)
- •Patients with urinary tract obstruction by tumor must meet the renal function criteria AND must have unimpeded urinary flow established via decompression of the obstructed portion of the urinary tract
- •Total bilirubin =< 1.5 x upper limit of normal for age
- •Peripheral absolute neutrophil count (ANC) >= 750/uL
- •Platelet count >= 75,000/uL (transfusion independent)
- •No evidence of uncontrolled infection
- •Patients must be able to undergo radiation therapy, if necessary, as specified in the protocol
- •Female patients of childbearing potential must have a negative pregnancy test
- •Female patients who are breast feeding must agree to stop breast feeding
- •Sexually active patients of childbearing potential must be willing to use effective contraception during therapy and for at least 1 month after treatment is completed
- •All patients and/or their parents or legal guardians must sign a written informed consent
- •All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
排除标准
- 未提供
研究组 & 干预措施
Arm I (chemotherapy, radiotherapy)
Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
干预措施: Cyclophosphamide (Drug)
Arm I (chemotherapy, radiotherapy)
Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
干预措施: Dactinomycin (Biological)
Arm I (chemotherapy, radiotherapy)
Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (chemotherapy, radiotherapy)
Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
干预措施: Questionnaire Administration (Other)
Arm I (chemotherapy, radiotherapy)
Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
干预措施: Radiation Therapy (Radiation)
Arm I (chemotherapy, radiotherapy)
Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
干预措施: Vincristine Sulfate (Drug)
Arm II (chemotherapy, radiotherapy)
Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
干预措施: Cyclophosphamide (Drug)
Arm II (chemotherapy, radiotherapy)
Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
干预措施: Dactinomycin (Biological)
Arm II (chemotherapy, radiotherapy)
Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
干预措施: Irinotecan Hydrochloride (Drug)
Arm II (chemotherapy, radiotherapy)
Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (chemotherapy, radiotherapy)
Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
干预措施: Questionnaire Administration (Other)
Arm II (chemotherapy, radiotherapy)
Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
干预措施: Radiation Therapy (Radiation)
Arm II (chemotherapy, radiotherapy)
Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
干预措施: Vincristine Sulfate (Drug)
结局指标
主要结局
Event Free Survival (EFS)
时间窗: 4 years
Probability of no relapse, secondary malignancy, or death after 4 year in the study
Overall Survival (OS)
时间窗: 4 years
Probability of being alive after 4 years in the study.
Response Rate (RR)
时间窗: Reporting Period 1 (Weeks 1 - 15)
Proportion of patients with complete or partial response. Complete Response (CR): Complete disappearance of the tumor confirmed at \> 4 weeks; Partial Response (PR): At least 64% decrease in volume compared to the baseline; Overall Response (OR) = CR + PR.
次要结局
- Overall Survival (OS) Probability VAC and Early (Week 4) Radiotherapy Compared to Delayed (Week 10) Radiotherapy, Using IRSIV for Historic Comparison(4 years)
- Incidence of Toxicity(Up to 15 weeks)
- Compare Event Free Survival (EFS) With Respect to the Level of % Change in FDG PET Maximum Standard Uptake Value (SUVmax) at Week 4(4 years)
- Incidence of Toxicity Related to VI Treatment in Patients With UGT1A1 Genotype(Weeks 4-9 (the first exposure to VI))
- Event Free Survival (EFS) Probability VAC and Early (Week 4) Radiotherapy Compared to Delayed (Week 10) Radiotherapy, Using IRSIV for Historic Comparison(4 years)
- Acute and Late Effects of VAC as Delivered on This Study to D9803 VAC(Up to 43 weeks)
- Compare Event Free Survival (EFS) With Respect to the Level of % Change in FDG PET Maximum Standard Uptake Value (SUVmax) at Week 15(4 years)
- Toxicity With CYP2B6 Genotypes(During the study)
- Local Failure(2 years)
- Event Free Survival (EFS) by PAX Status(4 years)
- Toxicity With GSTA1 and CYP2C9 Genotypes(During the study)
- Incidence of Bladder Dysfunction(3-6 years after enrollment)