Combination Chemotherapy Alone or With Radiation Therapy in Treating Children With Kidney Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high energy x-rays to damage tumor cells. It is not yet known whether combination chemotherapy alone or combination chemotherapy plus radiation therapy is more effective for childhood kidney cancer. PURPOSE: Phase III trial to compare the effectiveness of combination chemotherapy with or without radiation therapy in treating children who have kidney cancer.

Detailed Description
-----------------
OBJECTIVES: Increase survival rate of children with favorable histology (FH) Wilms' tumor and other childhood renal tumors. Determine whether loss of heterozygosity for chromosome 16q or 1p in tumor tissue is associated with a poorer prognosis in children with FH Wilms' tumor. Determine whether increased DNA content in tumor cells is associated with a poorer prognosis in children with FH Wilms' tumor. Decrease the acute and long-term morbidity in children with Wilms' tumor by limiting initial therapy and consistently using the same regimen (protocol NWTS-5/R) for patients who relapse following initial treatment. Improve overall and disease-free survival of patients with renal tumors of unfavorable histology, including Wilms' tumor with diffuse anaplasia and clear cell sarcoma of the kidney, using a new treatment regimen that includes etoposide (VP-16) and cyclophosphamide (CTX). Improve overall and disease-free survival in patients with malignant rhabdoid tumor of the kidney using a new treatment regimen that includes carboplatin, VP-16, and CTX. (The rhabdoid tumor stratum closed to accrual effective 07/13/2001) Provide data regarding loss of heterozygosity for chromosomes 11p15, 16q, and 1p, age at diagnosis, precursor lesions (perilobar, intralobar, nephroblastomatosis), bilaterality, and presence of congenital anomalies required for the completion of protocol A0026 (a case-control study of risk factors for Wilms' tumor). OUTLINE: This is a multicenter study. Patients are assigned to one of nine strata based on tumor histology, stage, tumor weight, and age. Stratum 1 (stage I favorable histology (FH) Wilms' tumor, under 24 months of age, and tumor weight less than 550 g): After nephrectomy, patients receive regimen EE-4A comprising dactinomycin (DACT) IV weekly on weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine (VCR) IV weekly on weeks 1-10, 12, 15, and 18. Stratum 2 (stage I FH Wilms' tumor and age 24 months and over or tumor weight at least 550 g; stage I focal anaplastic (FA) or diffuse anaplastic (DA) Wilms' tumor): Patients receive therapy as in stratum 1. Stratum 3 (stage II FH Wilms' tumor): Patients receive therapy as in stratum 1. Stratum 4 (stage III FH Wilms' tumor; stage II or III FA Wilms' tumor): After nephrectomy, patients receive regimen DD-4A comprising DACT IV weekly on weeks 0, 6, 12, 18, and 24; doxorubicin IV weekly on weeks 3, 9, 15, and 21; and VCR IV weekly on weeks 1-10, 12, 15, 18, 21, and 24. Patients also undergo abdominal radiotherapy. Stratum 5 (stage IV FH or FA Wilms' tumor): Patients receive chemotherapy as in stratum 4, abdominal radiotherapy, and whole lung radiotherapy (at the discretion of the investigator). Stratum 6 (stage V FH, FA, or DA Wilms' tumor ): After bilateral biopsy, patients with FH receive chemotherapy as in stratum 1 or 4. Patients with FA or DA receive chemotherapy as in stratum 7. Stratum 7 (stages I-IV clear cell sarcoma): After nephrectomy, patients receive VCR IV weekly on weeks 1, 2, 4-8, 10-13, 18, and 24; cyclophosphamide (CTX) IV over 1 hour on days 1-3 of weeks 6, 12, 18, and 24 and on days 1-5 of weeks 3, 9, 15, and 21; doxorubicin IV (beginning after CTX infusion) weekly on weeks 0, 6, 12, 18, and 24; and etoposide (VP-16) IV over 1 hour (beginning after CTX infusion) on days 1-5 of weeks 3, 9, 15, and 21. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning 24 hours after completion of chemotherapy and continuing until blood counts recover. Patients also undergo abdominal radiotherapy and whole lung radiotherapy (if pulmonary metastases are present). Stratum 8 (stages II-IV DA Wilms' tumor): Patients receive treatment as in stratum 7. Stratum 9 (stages I-IV rhabdoid tumor): After nephrectomy, patients receive carboplatin IV on days 1-2 and VP-16 IV over 1 hour (beginning after carboplatin infusion) on days 1-3 of weeks 0, 3, 9, 12, 18, and 21 and CTX IV over 1 hour on days 1-5 of weeks 6, 15, and 24. G-CSF is administered as in stratum 7. Patients also undergo radiotherapy. (The rhabdoid tumor stratum closed to accrual effective 07/13/2001.) After completion of chemotherapy, patients undergo second-look laparotomy and partial nephrectomy or wedge excision (if feasible). After second-look surgery, patients without persistent or residual disease resume chemotherapy. Patients are followed every 3 months for 5 years, every 6 months for 2 years, and then annually for 3 years. PROJECTED ACCRUAL: A total of 207 patients will be accrued for the treatment portion of this study. (The rhabdoid tumor stratum closed to accrual effective 07/13/2001.)

Official Title
-----------------
NATIONAL WILMS TUMOR STUDY-5 -- THERAPEUTIC TRIAL AND BIOLOGY STUDY

Conditions
-----------------
Kidney Cancer

Intervention / Treatment
-----------------
* Biological: dactinomycin
* Biological: filgrastim
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: etoposide
* Drug: vincristine sulfate
* Procedure: conventional surgery
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed stage I-V kidney cancer of one of the following histologies: Wilms' tumor, favorable histology Wilms' tumor, focal or diffuse anaplastic Clear cell sarcoma Rhabdoid tumor (The rhabdoid tumor stratum closed to accrual effective 07/13/2001) Prior nephrectomy or biopsy required Prior bilateral biopsy (preferably open) with bilateral staging and pathologic evaluation required for bilateral tumor Must begin study therapy within 5 days after nephrectomy (unless medically contraindicated) PATIENT CHARACTERISTICS: Age: Under 16 Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: Not pregnant Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy Surgery: See Disease Characteristics

Ages Eligible for Study
-----------------
Minimum Age: 0 Years
Maximum Age: 15 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Stratum 1<br>Stage I favorable histology (FH) Wilms' tumor, under 24 months of age, and tumor weight less than 550 g: After conventional surgery (nephrectomy), patients receive regimen EE-4A comprising dactinomycin (DACT) IV weekly on weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine sulfate (VCR) IV weekly on weeks 1-10, 12, 15, and 18. | Biological: dactinomycin<br> <br> Drug: vincristine sulfate<br> <br> Procedure: conventional surgery<br> <br> |
| Active Comparator: Stratum 2<br>Stage I FH Wilms' tumor and age 24 months and over or tumor weight at least 550 g; stage I focal anaplastic (FA) or diffuse anaplastic (DA) Wilms' tumor: Patients receive regimen EE-4A comprising dactinomycin (DACT) IV weekly on weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine sulfate (VCR) IV weekly on weeks 1-10, 12, 15, and 18. | Biological: dactinomycin<br> <br> Drug: vincristine sulfate<br> <br> |
| Active Comparator: Stratum 3<br>Stage II FH Wilms' tumor: Patients receive regimen EE-4A comprising dactinomycin (DACT) IV weekly on weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine sulfate (VCR) IV weekly on weeks 1-10, 12, 15, and 18. | Biological: dactinomycin<br> <br> Drug: vincristine sulfate<br> <br> |
| Active Comparator: Stratum 4<br>Stage III FH Wilms' tumor; stage II or III FA Wilms' tumor: After conventional surgery (nephrectomy), patients receive regimen DD-4A comprising dactinomycin DACT IV weekly on weeks 0, 6, 12, 18, and 24; doxorubicin hydrochloride IV weekly on weeks 3, 9, 15, and 21; and vincristine sulfate VCR IV weekly on weeks 1-10, 12, 15, 18, 21, and 24. Patients also undergo abdominal radiation therapy. | Biological: dactinomycin<br> <br> Drug: doxorubicin hydrochloride<br>* Source and Pharmacology: An anthracycline antibiotic isolated from cultures of Streptomyces peucetius. Binds to DNA and inhibits nucleic acid synthesis, with its major lethal effect occurring during the S phase of the cell cycle. Has some topoisomerase II inhibitory activity. Since it is primarily excreted by the liver, any liver impairment may enhance toxicity. 40% to 50% is excreted in the bile; <5% in the urine. The drug has a very short initial t½ of <20 minutes and a terminal t½ of 17 hours. Animal studies indicate cytotoxic levels persist in tissue for as long as 24 hours.<br>* Other names: (Adriamycin);Drug: vincristine sulfate<br> <br> Procedure: conventional surgery<br> <br> Radiation: radiation therapy<br> <br> |
| Active Comparator: Stratum 5<br>Stage IV FH or FA Wilms' tumor: patients receive regimen DD-4A comprising dactinomycin DACT IV weekly on weeks 0, 6, 12, 18, and 24; doxorubicin hydrochloride IV weekly on weeks 3, 9, 15, and 21; and vincristine sulfate VCR IV weekly on weeks 1-10, 12, 15, 18, 21, and 24. Patients also undergo abdominal radiation therapy, and whole lung radiation therapy (at the discretion of the investigator). | Biological: dactinomycin<br> <br> Drug: doxorubicin hydrochloride<br>* Source and Pharmacology: An anthracycline antibiotic isolated from cultures of Streptomyces peucetius. Binds to DNA and inhibits nucleic acid synthesis, with its major lethal effect occurring during the S phase of the cell cycle. Has some topoisomerase II inhibitory activity. Since it is primarily excreted by the liver, any liver impairment may enhance toxicity. 40% to 50% is excreted in the bile; <5% in the urine. The drug has a very short initial t½ of <20 minutes and a terminal t½ of 17 hours. Animal studies indicate cytotoxic levels persist in tissue for as long as 24 hours.<br>* Other names: (Adriamycin);Drug: vincristine sulfate<br> <br> |
| Active Comparator: Stratum 6<br>Stage V FH, FA, or DA Wilms' tumor: After bilateral conventional surgery (biopsy), patients with FH receive chemotherapy as in stratum 1 (dactinomycin IV weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine sulfate IV weeks 1-10, 12, 15, and 18) or 4 (dactinomycin IV weeks 0, 6, 12, 18, and 24; doxorubicin hydrochloride IV weeks 3, 9, 15, and 21; and vincristine sulfate VCR IV weeks 1-10, 12, 15, 18, 21, and 24). Patients with FA or DA receive chemotherapy as in stratum 7 (vincristine sulfate VCR IV weeks 1, 2, 4-8, 10-13, 18, and 24; cyclophosphamide sulfate (CTX) IV over 1 hour on days 1-3 of weeks 6, 12, 18, and 24 and on days 1-5 of weeks 3, 9, 15, and 21; doxorubicin hydrochloride IV (beginning after CTX infusion) weeks 0, 6, 12, 18, and 24; and etoposide (VP-16) IV over 1 hour (beginning after CTX infusion) on days 1-5 of weeks 3, 9, 15, and 21. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning 24 hours after completion of chemotherapy. | Biological: dactinomycin<br> <br> Biological: filgrastim<br> <br> Drug: cyclophosphamide<br> <br> Drug: doxorubicin hydrochloride<br>* Source and Pharmacology: An anthracycline antibiotic isolated from cultures of Streptomyces peucetius. Binds to DNA and inhibits nucleic acid synthesis, with its major lethal effect occurring during the S phase of the cell cycle. Has some topoisomerase II inhibitory activity. Since it is primarily excreted by the liver, any liver impairment may enhance toxicity. 40% to 50% is excreted in the bile; <5% in the urine. The drug has a very short initial t½ of <20 minutes and a terminal t½ of 17 hours. Animal studies indicate cytotoxic levels persist in tissue for as long as 24 hours.<br>* Other names: (Adriamycin);Drug: etoposide<br> <br> Drug: vincristine sulfate<br> <br> Procedure: conventional surgery<br> <br> |
| Active Comparator: Stratum 7<br>Stages I-IV clear cell sarcoma): After conventional surgery (nephrectomy), patients receive vincristine sulfate VCR IV weekly on weeks 1, 2, 4-8, 10-13, 18, and 24; cyclophosphamide sulfate (CTX) IV over 1 hour on days 1-3 of weeks 6, 12, 18, and 24 and on days 1-5 of weeks 3, 9, 15, and 21; doxorubicin hydrochloride IV (beginning after CTX infusion) weekly on weeks 0, 6, 12, 18, and 24; and etoposide (VP-16) IV over 1 hour (beginning after CTX infusion) on days 1-5 of weeks 3, 9, 15, and 21. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning 24 hours after completion of chemotherapy and continuing until blood counts recover. Patients also undergo abdominal radiotherapy and whole lung radiotherapy (if pulmonary metastases are present). | Biological: filgrastim<br> <br> Drug: doxorubicin hydrochloride<br>* Source and Pharmacology: An anthracycline antibiotic isolated from cultures of Streptomyces peucetius. Binds to DNA and inhibits nucleic acid synthesis, with its major lethal effect occurring during the S phase of the cell cycle. Has some topoisomerase II inhibitory activity. Since it is primarily excreted by the liver, any liver impairment may enhance toxicity. 40% to 50% is excreted in the bile; <5% in the urine. The drug has a very short initial t½ of <20 minutes and a terminal t½ of 17 hours. Animal studies indicate cytotoxic levels persist in tissue for as long as 24 hours.<br>* Other names: (Adriamycin);Drug: etoposide<br> <br> Procedure: conventional surgery<br> <br> Radiation: radiation therapy<br> <br> |
| Active Comparator: Stratum 8<br>Stages II-IV DA Wilms' tumor: After conventional surgery (nephrectomy), Patients receive treatment as in stratum 7 (patients receive vincristine sulfate VCR IV weekly on weeks 1, 2, 4-8, 10-13, 18, and 24; cyclophosphamide sulfate (CTX) IV over 1 hour on days 1-3 of weeks 6, 12, 18, and 24 and on days 1-5 of weeks 3, 9, 15, and 21; doxorubicin hydrochloride IV (beginning after CTX infusion) weekly on weeks 0, 6, 12, 18, and 24; and etoposide (VP-16) IV over 1 hour (beginning after CTX infusion) on days 1-5 of weeks 3, 9, 15, and 21. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning 24 hours after completion of chemotherapy and continuing until blood counts recover. Patients also undergo abdominal radiotherapy and whole lung radiotherapy (if pulmonary metastases are present). | Biological: filgrastim<br> <br> Drug: cyclophosphamide<br> <br> Drug: doxorubicin hydrochloride<br>* Source and Pharmacology: An anthracycline antibiotic isolated from cultures of Streptomyces peucetius. Binds to DNA and inhibits nucleic acid synthesis, with its major lethal effect occurring during the S phase of the cell cycle. Has some topoisomerase II inhibitory activity. Since it is primarily excreted by the liver, any liver impairment may enhance toxicity. 40% to 50% is excreted in the bile; <5% in the urine. The drug has a very short initial t½ of <20 minutes and a terminal t½ of 17 hours. Animal studies indicate cytotoxic levels persist in tissue for as long as 24 hours.<br>* Other names: (Adriamycin);Drug: etoposide<br> <br> Drug: vincristine sulfate<br> <br> Procedure: conventional surgery<br> <br> Radiation: radiation therapy<br> <br> |
| Active Comparator: Stratum 9<br>Stages I-IV rhabdoid tumor: After conventional surgery (nephrectomy), patients receive carboplatin IV on days 1-2 and VP-16 IV over 1 hour (beginning after carboplatin infusion) on days 1-3 of weeks 0, 3, 9, 12, 18, and 21 and CTX IV over 1 hour on days 1-5 of weeks 6, 15, and 24. Filgrastim G-CSF is administered as on stratum 7. Patients also undergo radiation therapy. After completion of chemotherapy, patients undergo second-look conventional surgery (laparotomy) and conventional surgery (partial nephrectomy or wedge excision if feasible). After conventional surgery (second-look surgery), patients without persistent or residual disease resume chemotherapy. | Biological: filgrastim<br> <br> Drug: etoposide<br> <br> Procedure: conventional surgery<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage I Wilms tumor, stage II Wilms tumor, stage III Wilms tumor, stage IV Wilms tumor, stage V Wilms tumor, clear cell sarcoma of the kidney