Treatment of Newly Diagnosed Higher Risk Favorable Histology Wilms Tumors
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 395
- 试验地点
- 419
- 主要终点
- Event Free Survival Probability
研究概览
简要总结
This phase III trial is studying how well combination chemotherapy with or without radiation therapy works in treating young patients with newly diagnosed stage III or stage IV Wilms' tumor. Drugs used in chemotherapy 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 more than one drug (combination chemotherapy) with or without radiation therapy may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To demonstrate that patients with Stage IV favorable histology (FH) Wilms tumor with pulmonary metastases only, who have complete resolution of the pulmonary lesions after 6 weeks of DD-4A chemotherapy (vincristine, dactinomycin, and doxorubicin), called Rapid Complete Responders (RCR), will have at least an 85% 4 year event-free survival (EFS) after therapy with additional DD-4A and without whole lung irradiation.
II. To demonstrate that Stage IV FH patients who do not have resolution of pulmonary metastases by Week 6, called Slow Incomplete Responders (SIR), will have a 4 year EFS of 85% with the addition of cyclophosphamide and etoposide to a modified Regimen DD-4A (Regimen M).
III. To improve the 4 year EFS to 75% for patients with Stage III or IV FH Wilms tumor with loss of heterozygosity (LOH) for chromosomes 1p and 16q.
SECONDARY OBJECTIVE:
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
- — 至 29 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be less than 30 years of age at the time of diagnosis
- •Prior to enrollment on AREN0533, all patients must have been enrolled on AREN03B2 for central pathology review. Stage III patients with LOH transferring from AREN0532 may be enrolled on this study. Eligible patients for AREN0533 must be:
- •Newly diagnosed Stage IV favorable histology Wilms tumor with or without LOH 1p and 16q or
- •Newly diagnosed Stage III favorable histology Wilms tumor with LOH for 1p and 16q transferring from AREN0532
- •Patients with bilateral Wilms tumors (Stage V) are not eligible for AREN0533 and should be directed to AREN0534
- •Patients must begin protocol therapy on AREN0533 by Day 14 after surgery or biopsy, unless medically contraindicated
- •The Karnofsky performance status must be >= 50 for patients > 16 years of age and the Lansky performance status must be >= 50 for patients =< 16 years of age
- •Patients cannot have had prior tumor-directed chemotherapy or radiotherapy except for patients transferring from AREN0532 or those treated for emergent issues, as medically indicated
- •Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age (must be submitted for central review by Day 7)
- •Serum glutamic oxaloacetic transaminase (SGOT) aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) < 2.5 x ULN for age (must be submitted for central review by Day 7)
- •Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram
- •Female patients of childbearing age must have a negative pregnancy test
- •Female patients who are lactating must agree to stop breast-feeding
- •Sexually active patients of childbearing potential must agree to use effective contraception
排除标准
- 未提供
研究组 & 干预措施
Treatment (chemotherapy, surgery, radiotherapy)
REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV. Patients with pulmonary and extra-pulmonary metastases at diagnosis undergo radiotherapy.
Patients with initially unresectable or incompletely resected tumors are reevaluated at week 6, and if resectable, undergo surgery and then proceed to either regimen DD4A or regimen M.
REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV.
REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV; vincristine IV; and dactinomycin IV and doxorubicin hydrochloride IV. Patients with pulmonary metastases only who are SIR also undergo whole lung radiotherapy.
干预措施: Cyclophosphamide (Drug)
Treatment (chemotherapy, surgery, radiotherapy)
REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV. Patients with pulmonary and extra-pulmonary metastases at diagnosis undergo radiotherapy.
Patients with initially unresectable or incompletely resected tumors are reevaluated at week 6, and if resectable, undergo surgery and then proceed to either regimen DD4A or regimen M.
REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV.
REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV; vincristine IV; and dactinomycin IV and doxorubicin hydrochloride IV. Patients with pulmonary metastases only who are SIR also undergo whole lung radiotherapy.
干预措施: Dactinomycin (Biological)
Treatment (chemotherapy, surgery, radiotherapy)
REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV. Patients with pulmonary and extra-pulmonary metastases at diagnosis undergo radiotherapy.
Patients with initially unresectable or incompletely resected tumors are reevaluated at week 6, and if resectable, undergo surgery and then proceed to either regimen DD4A or regimen M.
REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV.
REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV; vincristine IV; and dactinomycin IV and doxorubicin hydrochloride IV. Patients with pulmonary metastases only who are SIR also undergo whole lung radiotherapy.
干预措施: Vincristine Sulfate Liposome (Drug)
Treatment (chemotherapy, surgery, radiotherapy)
REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV. Patients with pulmonary and extra-pulmonary metastases at diagnosis undergo radiotherapy.
Patients with initially unresectable or incompletely resected tumors are reevaluated at week 6, and if resectable, undergo surgery and then proceed to either regimen DD4A or regimen M.
REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV.
REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV; vincristine IV; and dactinomycin IV and doxorubicin hydrochloride IV. Patients with pulmonary metastases only who are SIR also undergo whole lung radiotherapy.
干预措施: 3-Dimensional Conformal Radiation Therapy (Radiation)
Treatment (chemotherapy, surgery, radiotherapy)
REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV. Patients with pulmonary and extra-pulmonary metastases at diagnosis undergo radiotherapy.
Patients with initially unresectable or incompletely resected tumors are reevaluated at week 6, and if resectable, undergo surgery and then proceed to either regimen DD4A or regimen M.
REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV.
REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV; vincristine IV; and dactinomycin IV and doxorubicin hydrochloride IV. Patients with pulmonary metastases only who are SIR also undergo whole lung radiotherapy.
干预措施: Conventional Surgery (Procedure)
Treatment (chemotherapy, surgery, radiotherapy)
REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV. Patients with pulmonary and extra-pulmonary metastases at diagnosis undergo radiotherapy.
Patients with initially unresectable or incompletely resected tumors are reevaluated at week 6, and if resectable, undergo surgery and then proceed to either regimen DD4A or regimen M.
REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV.
REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV; vincristine IV; and dactinomycin IV and doxorubicin hydrochloride IV. Patients with pulmonary metastases only who are SIR also undergo whole lung radiotherapy.
干预措施: Etoposide (Drug)
Treatment (chemotherapy, surgery, radiotherapy)
REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV. Patients with pulmonary and extra-pulmonary metastases at diagnosis undergo radiotherapy.
Patients with initially unresectable or incompletely resected tumors are reevaluated at week 6, and if resectable, undergo surgery and then proceed to either regimen DD4A or regimen M.
REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV.
REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV; vincristine IV; and dactinomycin IV and doxorubicin hydrochloride IV. Patients with pulmonary metastases only who are SIR also undergo whole lung radiotherapy.
干预措施: Doxorubicin Hydrochloride (Drug)
结局指标
主要结局
Event Free Survival Probability
时间窗: At 4 years
Probability of no relapse, secondary malignancy, or death after 4 year in the study
Event Free Survival (EFS) Probability
时间窗: At 4 years
Probability of no relapse, secondary malignancy, or death after 4 year in the study.
Event Free Survival Probability
时间窗: 4 years
Probability of no relapse, secondary malignancy, or death after 4 year in the study.
次要结局
- Event Free Survival Associated With the Burden of Pulmonary Metastatic Disease(At 4 years)