Combination Chemotherapy Alone or With Radiation Therapy in Treating Children With Kidney Cancer
Condition: Kidney Cancer
MeSH terms: Kidney Neoplasms; Carcinoma, Renal Cell; Wilms Tumor
Study type: Interventional
Phase: Phase 3

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.)
    

Intervention name(s): dactinomycin; filgrastim; cyclophosphamide; doxorubicin hydrochloride; etoposide; vincristine sulfate; conventional surgery; radiation therapy
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Procedure; Radiation
Intervention description(s): 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.
Other intervention name(s): NSC #123127; (Adriamycin)
Intervention MeSH terms: Dactinomycin; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine
Primary purpose: Treatment
Keywords: 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