Treatment for Patients With Bilateral, Multicentric, or Bilaterally-Predisposed Unilateral Wilms Tumor
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 249
- 试验地点
- 338
- 主要终点
- Event-Free Survival (EFS)
研究概览
简要总结
This phase III trial studies how well combination chemotherapy and surgery work in treating young patients with Wilms tumor. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any tumor cells that remain after surgery.
详细描述
OBJECTIVES:
I. To improve 4-year event-free survival (EFS) to 73% for young patients with bilateral Wilms tumor (BWT).
II. To prevent complete removal of at least one kidney in 50% of patients with BWT by using prenephrectomy 3-drug chemotherapy induction with vincristine (vincristine sulfate), dactinomycin, and doxorubicin (doxorubicin hydrochloride).
III. To evaluate the efficacy of chemotherapy in preserving renal units in children with diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) and preventing Wilms tumor development.
IV. To facilitate partial nephrectomy in lieu of nephrectomy in 25% of children with unilateral tumors and aniridia, Beckwith-Wiedemann syndrome (BWS), hemihypertrophy or other overgrowth syndromes, by using prenephrectomy 2-drug chemotherapy induction with vincristine and dactinomycin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •The patient must have one of the following conditions to be eligible:
- •Synchronous bilateral Wilms tumors**; or
- •Unilateral Wilms tumor and aniridia, Beckwith-Wiedemann Syndrome, idiopathic hemihypertrophy, Simpson-Golabi-Behmel-Syndrome, Denys-Drash Syndrome or other associated genitourinary anomalies associated with bilateral Wilms tumor, such as hypospadias and undescended testis (to be eligible, these patients must not undergo any nephrectomy at diagnosis; note-horseshoe kidney is not associated with bilateral Wilms tumor and these patients should go on the appropriate unilateral Wilms tumor study); or
- •Multicentric Wilms tumor (any age) (to be eligible, these patients must not undergo any nephrectomy at diagnosis); or
- •Unilateral Wilms tumor with contralateral nephrogenic rest(s) (any size) in a child under one year of age (to be eligible, these patients must not undergo any nephrectomy at diagnosis); or
- •Diffuse hyperplastic perilobar nephroblastomatosis (unilateral or bilateral) defined by central radiological review; or
- •Wilms tumor arising in a solitary kidney (patients with metachronous Wilms tumor are not eligible)
- •The AREN0534 study uses the guideline that Wilms tumor with a single lesion 1 cm or greater in the contralateral kidney or multiple lesions (of any size) in the contralateral kidney should be treated on the synchronous bilateral Wilms tumor stratum; patients with an isolated lesion less than 1 cm in the contralateral kidney should be treated on the appropriate study for unilateral Wilms tumor OR on the unilateral Wilms tumor/contralateral nephrogenic rest stratum of this study if they have not undergone nephrectomy and are under one year of age
- •Loss of heterozygosity (LOH) results-which are used in the unilateral Wilms tumor studies-are not a requirement for enrollment on AREN0534; blood samples can be submitted but will not be used to direct AREN0534 therapy
- •Specimens/materials must be submitted for central review by day 7; for enrollment on AREN0534, unless a biopsy was done, the submission requirements at enrollment on AREN03B2 refer to imaging studies; tissue samples are only required if a surgical procedure (biopsy or nephrectomy) was performed at the time of enrollment on AREN03B2
- •Patients must begin protocol therapy on AREN0534 by day 14 following surgery or diagnosis by initial computed tomography (CT)/magnetic resonance imaging (MRI), unless medically contraindicated
- •Karnofsky performance status must be >= 50% for patients > 16 years of age and Lansky performance status must be >= 50% (for patients =< 16 years of age
- •Patients must not have received systemic chemotherapy or radiation therapy prior to treatment on this study
- •Patients with unilateral Wilms tumor and aniridia, Beckwith-Wiedemann Syndrome, idiopathic hemihypertrophy, Simpson-Golabi-Behmel-Syndrome, Denys-Drash Syndrome or other associated genitourinary anomalies; or multicentric or unilateral Wilms tumor with contralateral nephrogenic rest(s) (any size) in a child under 1 year of age who undergo a nephrectomy at diagnosis are not eligible for this study and should be directed to a unilateral Wilms tumor study
- •Total bilirubin =< 1.5 times upper limit of normal (ULN) for age
- •Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 times upper limit of normal (ULN) for age
- •Shortening fraction >= 27% by echocardiogram, OR ejection fraction >= 50% by radionuclide angiogram
- •(Cardiac function does not need to be assessed in patients who will not receive doxorubicin as part of their initial therapy on this study [i.e., patients who start on regimen EE-4A])
- •Female patients of childbearing age must have a negative pregnancy test
- •Female patients who are lactating must agree to stop breastfeeding
- •Sexually active patients of childbearing potential must agree to use effective contraception
- •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
- •No concurrent aprepitant
排除标准
- 未提供
研究组 & 干预措施
Arm 1 (Bilateral Wilms Tumors)
Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy.
干预措施: Dactinomycin (Biological)
Arm 1 (Bilateral Wilms Tumors)
Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy.
干预措施: Doxorubicin Hydrochloride (Drug)
Arm 3 (DHPLN)
Patients with this rare disease are diagnosed based on cross-sectional imaging characteristics and undergo 2 drug chemotherapy (Regimen;VA). Patients are reassessed at 6 weeks and 12 weeks. If disease has responded or stayed stable chemotherapy is completed for 19 weeks (Regimen EE4A). If disease has progress a biopsy is performed to assess histology and adjust therapy based on the biopsy. This therapy may include, nephrectomy, chemotherapy or radiation therapy.
干预措施: Therapeutic Conventional Surgery (Procedure)
Arm 3 (DHPLN)
Patients with this rare disease are diagnosed based on cross-sectional imaging characteristics and undergo 2 drug chemotherapy (Regimen;VA). Patients are reassessed at 6 weeks and 12 weeks. If disease has responded or stayed stable chemotherapy is completed for 19 weeks (Regimen EE4A). If disease has progress a biopsy is performed to assess histology and adjust therapy based on the biopsy. This therapy may include, nephrectomy, chemotherapy or radiation therapy.
干预措施: Vincristine Sulfate (Drug)
Arm 1 (Bilateral Wilms Tumors)
Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy.
干预措施: Vincristine Sulfate (Drug)
Arm 2 (Unilateral High Risk tumors bilaterally predisposed)
Patients start with either 2 drug or three drug chemotherapy (Regimen VA, VAD) and are evaluated a 6 and 12 weeks for feasibility of undergoing a partial nephrectomy. At week 12 definitive surgery takes place followed by chemotherapy.
干预措施: Dactinomycin (Biological)
Arm 3 (DHPLN)
Patients with this rare disease are diagnosed based on cross-sectional imaging characteristics and undergo 2 drug chemotherapy (Regimen;VA). Patients are reassessed at 6 weeks and 12 weeks. If disease has responded or stayed stable chemotherapy is completed for 19 weeks (Regimen EE4A). If disease has progress a biopsy is performed to assess histology and adjust therapy based on the biopsy. This therapy may include, nephrectomy, chemotherapy or radiation therapy.
干预措施: Dactinomycin (Biological)
Arm 1 (Bilateral Wilms Tumors)
Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy.
干预措施: Radiation Therapy (Radiation)
Arm 1 (Bilateral Wilms Tumors)
Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy.
干预措施: Therapeutic Conventional Surgery (Procedure)
Arm 2 (Unilateral High Risk tumors bilaterally predisposed)
Patients start with either 2 drug or three drug chemotherapy (Regimen VA, VAD) and are evaluated a 6 and 12 weeks for feasibility of undergoing a partial nephrectomy. At week 12 definitive surgery takes place followed by chemotherapy.
干预措施: Radiation Therapy (Radiation)
Arm 2 (Unilateral High Risk tumors bilaterally predisposed)
Patients start with either 2 drug or three drug chemotherapy (Regimen VA, VAD) and are evaluated a 6 and 12 weeks for feasibility of undergoing a partial nephrectomy. At week 12 definitive surgery takes place followed by chemotherapy.
干预措施: Therapeutic Conventional Surgery (Procedure)
Arm 3 (DHPLN)
Patients with this rare disease are diagnosed based on cross-sectional imaging characteristics and undergo 2 drug chemotherapy (Regimen;VA). Patients are reassessed at 6 weeks and 12 weeks. If disease has responded or stayed stable chemotherapy is completed for 19 weeks (Regimen EE4A). If disease has progress a biopsy is performed to assess histology and adjust therapy based on the biopsy. This therapy may include, nephrectomy, chemotherapy or radiation therapy.
干预措施: Radiation Therapy (Radiation)
Arm 2 (Unilateral High Risk tumors bilaterally predisposed)
Patients start with either 2 drug or three drug chemotherapy (Regimen VA, VAD) and are evaluated a 6 and 12 weeks for feasibility of undergoing a partial nephrectomy. At week 12 definitive surgery takes place followed by chemotherapy.
干预措施: Doxorubicin Hydrochloride (Drug)
Arm 2 (Unilateral High Risk tumors bilaterally predisposed)
Patients start with either 2 drug or three drug chemotherapy (Regimen VA, VAD) and are evaluated a 6 and 12 weeks for feasibility of undergoing a partial nephrectomy. At week 12 definitive surgery takes place followed by chemotherapy.
干预措施: Vincristine Sulfate (Drug)
Arm 3 (DHPLN)
Patients with this rare disease are diagnosed based on cross-sectional imaging characteristics and undergo 2 drug chemotherapy (Regimen;VA). Patients are reassessed at 6 weeks and 12 weeks. If disease has responded or stayed stable chemotherapy is completed for 19 weeks (Regimen EE4A). If disease has progress a biopsy is performed to assess histology and adjust therapy based on the biopsy. This therapy may include, nephrectomy, chemotherapy or radiation therapy.
干预措施: Doxorubicin Hydrochloride (Drug)
结局指标
主要结局
Event-Free Survival (EFS)
时间窗: 4 years from study enrollment
Probability of no relapse, secondary malignancy, or death whichever occurs first
Kidney Preservation After Preoperative Chemotherapy
时间窗: 12 weeks from study entry
Prevention of complete removal of at least one kidney in 50% of patients with bilateral Wilms tumor (BWT).
Number of Patients Without Complete Removal of at Least One Kidney
时间窗: 12 weeks from the study entry
To evaluate the efficacy of chemotherapy in preserving renal units in children with diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) and preventing Wilms tumor development.
Percentage of Patients Who Experienced Partial Nephrectomy After Preoperative Chemotherapy
时间窗: 12 weeks from study entry
Percentage of patients who experienced partial nephrectomy in lieu of nephrectomy in 25% of children with unilateral tumors and aniridia, Beckwith-Wiedemann syndrome (BWS), hemihypertrophy or other overgrowth syndromes, by using prenephrectomy 2-drug chemotherapy induction with vincristine and dactinomycin.
Percentage of Patients Who Had Definitive Surgical Treatment
时间窗: 12 weeks from study entry
Percentage of Bilateral Wilms Tumor (BWT) patients who undergo definitive surgery by week 12 after initiation of chemotherapy.
次要结局
未报告次要终点