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

Children's Oncology Group

Status and phase

Completed

Phase 3

Conditions

Kidney Cancer

Treatments

Drug: carboplatin

Procedure: conventional surgery

Biological: dactinomycin

Drug: etoposide

Drug: cyclophosphamide

Biological: filgrastim

Radiation: radiation therapy

Drug: doxorubicin hydrochloride

Drug: vincristine sulfate

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00002610

9444

CCG-4942 (Other Identifier)

CDR0000063900 (Other Identifier)

COG-Q9402 (Other Identifier)

NWTS-5/R (Other Identifier)

NWTS-Q9402 (Other Identifier)

INT-0152

POG-9444 (Other Identifier)

Details and patient eligibility

About

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. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. It is not yet known which therapy regimen is most effective for treating patients with kidney tumors.

PURPOSE: Phase III trial to compare the effectiveness of chemotherapy with or without radiation therapy, surgery, and/or peripheral stem cell or bone marrow transplantation in treating young patients with kidney tumors.

Full description

OBJECTIVES:

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.
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.
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.
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.

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.

PROJECTED ACCRUAL: Not specified

Enrollment

203 patients

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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)

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/mm^3
Platelet count at least 100,000/mm^3

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

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

Trial design

203 participants in 4 patient groups

STRATUM A

Experimental group

Description:

Treatment of children in Stratum A will be determined by the site of relapse and the presence of microscopic or gross residual disease after attempted surgical excision of the relapse.

Treatment:

Drug: vincristine sulfate

Drug: doxorubicin hydrochloride

Procedure: conventional surgery

Biological: dactinomycin

Radiation: radiation therapy

Stratum B

Experimental group

Description:

All children who received combination chemotherapy with Regimen EE - 4A as their initial therapy for Wilms tumor will receive Regimen I and radiation therapy to the site of recurrence. All patients will receive prophylactic trimethoprim /sulfamethoxazole

Treatment:

Drug: vincristine sulfate

Drug: doxorubicin hydrochloride

Biological: filgrastim

Procedure: conventional surgery

Drug: cyclophosphamide

Drug: etoposide

Radiation: radiation therapy

STRATUM C

Experimental group

Description:

All children who received combination chemotherapy with Regimen DD - 4A as their initial therapy for Wilms tumor will be treated with the following chemotherapy. All patients will receive prophylactic trimethoprim/sulfamethoxazole

Treatment:

Biological: filgrastim

Procedure: conventional surgery

Drug: cyclophosphamide

Drug: etoposide

Radiation: radiation therapy

Drug: carboplatin

STRATUM D

Experimental group

Description:

Six week cycles of chemotherapy will be given to all patients who do not have progressive disease at the time of each week 0 re-evaluation.

Treatment: