Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Chemotherapy With or Without Surgery, Radiation Therapy, or Stem Cell Transplantation in Treating Young Patients With Kidney Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Completed 21 and under at diagnosis NCI COG-Q9402 NWTS-Q9402, CCG-4942, POG-9444, INT-0152, NWTS-5/R, NCT00002610, Q9402

Objectives

1. Determine the 2-year second-event-free survival after vincristine (VCR) and dactinomycin (DACT) with or without doxorubicin (DOX), depending on the site of relapse and presence of microscopic residual disease, in children with relapsed Wilm's tumor previously treated with nephrectomy alone as initial therapy.
2. Determine whether the 2-year second-event-free survival after intensive doxorubicin, etoposide (VP-16), cyclophosphamide (CTX), and carboplatin (CBDCA) plus radiotherapy to residual disease is at least 40% higher in patients with relapsed Wilm's tumor previously treated with Regimen EE-4A as initial therapy and without loss of heterozygosity for chromosomes 16q and 1p and increased DNA content in tumor cells than for similarly treated patients with loss of heterozygosity for chromosome 16q or 1p or increased DNA content in tumor cells.
3. Determine whether the 4-year post-relapse survival after intensive VP-16, CTX, and CBDCA is at least 40% higher in patients with relapsed Wilm's tumor previously treated with Regimen DD-4A as initial therapy and without loss of heterozygosity for chromosomes 16q and 1p and increased DNA content in tumor cells than for similarly treated patients with loss of heterozygosity for chromosome 16q or 1p or increased DNA content in tumor cells.
4. Determine whether the rates of complete and partial response exceed 20% in patients with relapsed clear cell sarcoma of the kidney or diffuse anaplastic Wilms' tumor treated with CBDCA combined with VP-16.

Entry Criteria

Disease Characteristics:

• Diagnosis of Wilms' tumor
  • Eligible subtypes:
    • Favorable histologies
    • Anaplastic histologies
    • Clear cell sarcoma of the kidney
    • Rhabdoid tumor of the kidney



• Relapsed disease after entry on protocol NWTS-5 (NWTS-Q9401)

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• At least 2 weeks since prior chemotherapy and recovered

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior therapy for relapsed Wilms' tumor
• Recovered from the toxic effects of any other prior therapy

Patient Characteristics:

Age:

• 21 and under at original diagnosis

Performance status:

• Not specified

Life expectancy:

• At least 4 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• Bilirubin no greater than 1.5 times normal
• SGOT or SGPT less than 2.5 times normal

Renal:

• Creatinine no greater than 1.5 times normal

  OR

• Creatinine clearance or GFR at least 70 mL/min

Cardiovascular:

• Shortening fraction at least 27% by echocardiogram

  OR

• Ejection fraction greater than 50% by echocardiogram or MUGA scan

Other:

• Not pregnant
• Fertile patients must use effective contraception

Expected Enrollment

Not specified

Outline

This is a multicenter study.

Patients are assigned to a treatment group based on initial therapy and histology. Patients under age 2 at diagnosis who were previously treated with nephrectomy as initial therapy for stage I favorable histology Wilms' tumor weighing less than 550 grams are assigned to group A. Patients who received Regimen EE-4A as initial therapy for Wilms' tumor are assigned to group B. Patients who received Regimen DD-4A as initial therapy for Wilms' tumor are assigned to group C. Patients with clear cell sarcoma of the kidney or diffuse anaplastic Wilms' tumor are assigned to group D.

Group A

• Treatment is determined by site of relapse and the presence of microscopic or gross residual disease after attempted resection of relapsed disease. Children with suspected intra-abdominal recurrence undergo exploratory surgery to determine the site of recurrence and to obtain tissue for microscopic examination. Patients with stage I disease after recurrence are treated with regimen EE-4A. Patients with stage II or III disease are treated with regimen DD-4A.
  • Regimen EE-4A: Patients receive dactinomycin (DACT) IV on weeks 0, 3, 6, 9, 12, 15, and 18 and vincristine (VCR) IV on weeks 1-10, 12, 15, and 18 in the absence of disease progression.
  • Regimen DD-4A: Patients receive DACT IV on weeks 0, 6, 12, 18, and 24; VCR IV weekly on weeks 1-10, 12, 15, 18, 21, and 24; doxorubicin (DOX) IV on weeks 3, 9, 15, and 21; and abdominal radiotherapy in the absence of disease progression.

Group B

• Patients undergo resection. After resection, patients receive regimen I comprising DOX IV on weeks 0, 6, 12, 18, and 24; VCR IV on weeks 1, 2, 4, 5-8, 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; and etoposide (VP-16) IV over 1 hour (after CTX infusion) on days 1-5 of weeks 3, 9, 15, and 21 in the absence of disease progression. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning 24 hours after completion of chemotherapy and continuing until blood counts recover. Patients undergo radiotherapy to site of recurrence beginning within 1 week after initiation of chemotherapy.

Group C

• Induction: Patients receive CTX IV over 1 hour on days 1-5 of weeks 0 and 3; VP-16 IV over 1 hour (after CTX infusion) on days 1-5 of weeks of 0 and 3 and on days 1-3 of weeks 6 and 9; and carboplatin (CBDCA) IV over 6 hours on days 1 and 2 of weeks 6 and 9 in the absence of disease progression. G-CSF is administered SC beginning 24 hours after completion of CTX/VP-16 or CBDCA/VP-16 and continuing until blood counts recover.



• Surgery: Patients with detectable disease undergo resection on week 13. If complete resection is not achieved or if it is deemed impossible, resection must be attempted no later than 3 weeks after consolidation radiotherapy.



• Consolidation: Beginning within 9 days of surgery, patients receive CTX IV over 1 hour on days 1-5 of week 1; VP-16 IV over 1 hour (after CTX infusion) on days 1-5 of week 1 and on days 1-3 of week 4; CBDCA IV over 6 hours on days 1 and 2 of week 4; G-CSF as in induction; and radiotherapy in the absence of disease progression. Patients with complete or partial response after resection and/or radiotherapy proceed to maintenance therapy.



• Maintenance: Patients receive CTX IV over 1 hour on days 1-5 of weeks 0 and 3; VP-16 IV over 1 hour on days 1-5 of weeks 0 and 3 and on days 1-3 of weeks 6 and 9; CBDCA IV over 6 hours on days 1 and 2 of weeks 6 and 9; and G-CSF as in induction. Treatment continues every 12 weeks for 6 courses in the absence of disease progression.

Group D

• Patients receive CBDCA IV over 6 hours on days 1 and 2 and VP-16 IV over 1 hour (after CBDCA infusion) on days 1-3 of weeks 0 and 3. Treatment continues weekly for 6 courses in the absence of disease progression.

Patients are followed every 3 months for 15 months, every 6 months for 1 year, and then annually for 3 years.

Green DM, Cotton CA, Malogolowkin M, et al.: Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: a report from the National Wilms Tumor Study Group. Pediatr Blood Cancer 48 (5): 493-9, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Daniel Green, MD, Protocol chair		Ph: 716-845-2334; 800-685-6825

Registry Information
Official Title		NATIONAL WILMS TUMOR STUDY-5 -- TREATMENT OF RELAPSED PATIENTS
Trial Start Date		2002-05-31
Registered in ClinicalTrials.gov		NCT00002610
Date Submitted to PDQ		1995-06-16
Information Last Verified		2003-04-02
NCI Grant/Contract Number		CA13539, CA30969, CA42326

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