Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

All Conditions

Symptoms and General Pathology

Rare Diseases

Wilms Tumor

Neoplasms by Histologic Type

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Genetic Diseases, Inborn

Wilms' Tumor

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Dermatologic Agents

Carboplatin

Irinotecan

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Vincristine

Daunorubicin

Dactinomycin

Etoposide phosphate

Podophyllotoxin

Cactinomycin

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Topoisomerase I Inhibitors

Tubulin Modulators

Antimitotic Agents

Keratolytic Agents

Patients receive the EE-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, \& 15 of each cycle. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.

Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive six cycles of the EE-4A regimen as in STAGE I FHWT Arm I. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.

Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, \& 9, vincristine IV on days 1, 8, \& 15 of cycles 2-3 and day 1 of cycles 4-9, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.

Patients receive one cycle of the EE-4A regimen as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of the VIVA regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, and 9, vincristine IV on days 1, 8, and 15 of cycles 2-3 and day 1 of cycles 4-8, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.

Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, and 15. Patients receive cycles 2-7 of the EE-4A regimen as in STAGE I FHWT Arm I. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.

Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.

Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of the DD-4A regimen: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 and vincristine IV on days 1, 8, and 15. Patients receive cycle 2 treatment of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.

Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.

Patients receive the MVI regimen: Vincristine IV on days 1, 8, \& 15 of cycle 3, days 8 \& 15 of cycle 4, and day 1 of cycles 5 \& 7-13, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, doxorubicin IV over 3-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 4 and 6, irinotecan IV over 90 minutes daily on days 1-5 of cycles 5, 8, 10 \& 12, and etoposide IV over 60-120 minutes daily on days 1-5 of cycle 6. Treatment repeats every 21 days for 11 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients receive the M regimen: Cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, etoposide IV over 60-120 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, vincristine IV on days 8 \& 15 of cycles 3 \& 4 and day 1 of cycles 5, 6, 8, 10, \& 11, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 5, 6, 8, 10, \& 11, and doxorubicin IV over 3-15 minutes of cycles 5, 6, 8, 10, \& 11. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.

Patients receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.

Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients in Stage IV Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-7 of the EE-4A regimen as in STAGE I FHWT Arm I above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.

Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients in Stage IV Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients in Stage IV Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients in Stage IV Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.

Patients in Stage IV Arm VA receive cycles 5-9 of the DD-4A regimen as in STAGE II FHWT Arm II above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.

Patients in Stage IV Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients in Stage IV Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients in Stage IV Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients in Stage IV Extrapulmonary Arm I receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients in Stage IV Extrapulmonary Arm II receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients in Stage IV Extrapulmonary Arm III receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients in Stage IV Extrapulmonary Arm IV receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients in Stage IV Extrapulmonary Arm IX receive cycles 5-13 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients in Stage IV Extrapulmonary Arm V receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients in Stage IV Extrapulmonary Arm VI receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients in Stage IV Extrapulmonary Arm VII receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-4 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients in Stage IV Extrapulmonary Arm VIII receive the UH-3 regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arm II above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients in Stage IV Extrapulmonary Arm X receive cycles 5-11 of the M regimen as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive cycles 3-9 of the DD-4A regimen as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arms V and VA above. Patients also undergo CT, CT/MRI, ultrasound, and X-ray imaging throughout the trial.

Stage IV patients receive cycles 1-2 of the DD-4A regimen as in STAGE II FHWT and STAGE III FHWT Arm II above. Patients receive the MVI regimen as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT/MRI, ultrasound, X-ray, and bone scan/PET scans throughout the trial.

Bone Scan

Computed Tomography

Magnetic Resonance Imaging

Nephrectomy

Patient Observation

Positron Emission Tomography

Ultrasound Imaging

X-Ray Imaging

Elizabeth A Mullen

This phase III trial studies using risk factors in determining treatment for children with favorable tissue (histology) Wilms tumors (FHWT). Wilms Tumor is the most common type of kidney cancer in children, and FHWT is the most common subtype. Previous large clinical trials have established treatment plans that are likely to cure most children with FHWT, however some children still have their cancer come back (called relapse) and not all survive. Previous research has identified features of FHWT that are associated with higher or lower risks of relapse. The term "risk" refers to the chance of the cancer coming back after treatment. Using results of tumor histology tests, biology tests, and response to therapy may be able to improve treatment for children with FHWT.

A Study Using Risk Factors to Determine Treatment for Children With Favorable Histology Wilms Tumors (FHWT)

Risk Adapted Treatment of Unilateral Favorable Histology Wilms Tumors (FHWT)

Children's Oncology Group

Patients undergo nephrectomy only. If they meet criteria, they are then observed periodically for 5 years. Patients with recurrent disease undergo surgery (immediate or delayed) and receive chemotherapy as in stratum III. Patients with no metachronous renal disease receive radiotherapy. Patients with metachronous disease undergo renal-sparing surgery and chemotherapy as in stratum III, but no radiotherapy. Treatment continues for up to 25 weeks. Additionally, patients undergo chest X-ray, CT or MRI, ultrasound, echocardiography, and blood sample collection throughout the study.

Patients undergo nephrectomy. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1, every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 doses of doxorubicin. Treatment continues for up to 25 weeks. Additionally, patients undergo chest X-ray, CT or MRI, ultrasound, echocardiography, and blood sample collection throughout the study.

Patients undergo nephrectomy, if feasible, or biopsy. For patients who undergo biopsy only, definitive surgery is undertaken at week 7 or 13. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1 every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 dose of doxorubicin hydrochloride. Patients undergo radiotherapy over 5-7 days after nephrectomy. Treatment continues for up to 25 weeks. Additionally, patients undergo chest X-ray, CT or MRI, ultrasound, echocardiography, and blood sample collection throughout the study.

3-Dimensional Conformal Radiation Therapy

Biospecimen Collection

Chest Radiography

Doxorubicin Hydrochloride

Echocardiography

Therapeutic Conventional Surgery

Vincristine Sulfate

This phase III trial is studying vincristine, dactinomycin, and doxorubicin with or without radiation therapy or observation only to see how well they work in treating patients undergoing surgery for newly diagnosed stage I, stage II, or stage III Wilms' tumor. Drugs used in chemotherapy, such as vincristine, dactinomycin, and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors.Giving these treatments after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient.

PRIMARY OBJECTIVES:

I. Evaluate the overall and event-free survival of younger patients with newly diagnosed stage I favorable histology Wilms' tumor (\< 2 years of age and \< 550gms) treated with nephrectomy only (very low risk), or with newly diagnosed stage III favorable histology Wilms tumor with possible nephrectomy followed by vincristine, dactinomycin, doxorubicin hydrochloride, and radiotherapy (standard risk).

SECONDARY OBJECTIVES:

I. Determine the effects of adding doxorubicin hydrochloride to the regimen for patients with stage I or II favorable histology found to have a high-risk biological marker.

II. Determine whether the omission of adjuvant therapy increases the incidence of contralateral kidney lesions in patients with very low-risk disease treated by nephrectomy and observation only.

III. Determine whether the omission of adjuvant therapy increases the incidence of renal failure in patients with very low-risk disease who have metachronous relapse.

IV. Correlate study outcomes in patients with standard-risk disease with biological data from tissue collections on protocol study COG-AREN03B2.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical and biological risk factors (very low risk vs standard risk).

STRATUM I: (very low-risk disease) Patients undergo nephrectomy only. If they meet criteria, they are then observed periodically for 5 years. Patients with recurrent disease undergo surgery (immediate or delayed) and receive chemotherapy as in stratum III. Patients with no metachronous renal disease receive radiotherapy. Patients with metachronous disease undergo renal-sparing surgery and chemotherapy as in stratum III, but no radiotherapy. Treatment continues for up to 25 weeks.

STRATUM II: (standard-risk, stage I or II disease with adverse biological marker) Patients undergo nephrectomy. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1, every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 doses of doxorubicin. Treatment continues for up to 25 weeks.

STRATUM III: (standard-risk, stage III disease) Patients undergo nephrectomy, if feasible, or biopsy. For patients who undergo biopsy only, definitive surgery is undertaken at week 7 or 13. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1 every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 dose of doxorubicin hydrochloride. Patients undergo radiotherapy over 5-7 days after nephrectomy. Treatment continues for up to 25 weeks.

Additionally, patients undergo chest X-ray, computed tomography (CT) or magnetic resonance imaging (MRI), ultrasound, echocardiography, and blood sample collection throughout the study.

After completion of study treatment, patients are followed periodically for up to 8 years.

Vincristine, Dactinomycin, and Doxorubicin With or Without Radiation Therapy or Observation Only in Treating Younger Patients Who Are Undergoing Surgery for Newly Diagnosed Stage I, Stage II, or Stage III Wilms' Tumor

Treatment for Very Low and Standard Risk Favorable Histology Wilms Tumor

Probability of no relapse, secondary malignancy, or death after 4 year in the study.

Probability of being alive after 4 years in the study.

Number of contralateral kidney lesions during follow-up.

Number of renal failures defined as requiring dialysis or renal transplant as determined by low GFR during follow-up

National Cancer Institute (NCI)

Adverse Events were reported for eligible patients only.

Very Low Risk Disease

Low risk, stage I or II, no loss of heterozygosity (LOH).

Low Risk, Stage I or II, no LOH

Standard Risk, Stage I or II, with loss of heterozygosity (LOH).

Standard Risk, Stage I or II, With LOH

Standard Risk, Stage III

High Risk

Patients who have either Very Low Risk Disease, Low Risk Stage I or II no LOH, and Standard Risk, Stage I or II with LOH prior to final Risk Group Assignment.

Stage I or II

Patients who have either Standard Risk, Stage III and High Risk Patients prior to final Risk Group Assignment.

Stage III

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Stage I or II: Patients who have either Very Low Risk Disease, Low Risk Stage I or II no LOH, and Standard Risk, Stage I or II with LOH prior to final Risk Group Assignment. Stage III: Patients who have either Standard Risk, Stage III and High Risk Patients prior to final Risk Group Assignment.

Results Reporting Coordinator

Very Low Risk

Eligible very low risk or standard risk patients

Event Free Survival Probability

Overall Survival (OS) Probability

Very low risk patients treated by nephrectomy and observation only.

Incidence of Contralateral Kidney Lesions

Very low risk patients that have metachronous relapse.

Incidence of Renal Failure

Patients who have either Very Low Risk Disease, Low Risk Stage I or II no LOH, and Standard Risk, Stage I or II with LOH prior to final Risk Group Assignment

Stage I/II

Treatment arm. Nephrectomy and re-evaluation,very low-risk disease.

Treatment arm. Low risk, stage I or II, no loss of heterozygosity (LOH).

Treatment arm. Standard Risk, Stage I or II with LOH.

Standard Risk, Stage I or II With LOH

Initial Staging

Final Risk Group Assignment

Hyperplasia

Beckwith-Wiedemann Syndrome

Rhabdoid Tumor

Congenital Abnormalities

Abnormalities, Multiple

Chromosome Disorders

Fetal Thalidomide Syndrome

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.

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.

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.

Radiation Therapy

Peter F Ehrlich

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.

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.

V. To have 75% of patients with BWT undergo definitive surgical treatment by 12 weeks after initiation of chemotherapy.

OUTLINE: Patients are assigned to 1 of 3 arms.

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.

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.

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.

VAD REGIMEN: Patients receive vincristine sulfate intravenously (IV) over 1 minute on days 1, 8, 15, 22, 29, and 36 (weeks 1-6) and dactinomycin IV and doxorubicin hydrochloride IV over 15-120 minutes on days 1 and 22 (weeks 1 and 4).

EE4A REGIMEN: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 22, 29, and 36 (weeks 1-6) and dactinomycin IV over 1-5 minutes on days 1 and 22 (weeks 1 and 4).

After completion of study treatment, patients are followed up periodically for 10 years.

Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor

Treatment for Patients With Bilateral, Multicentric, or Bilaterally-Predisposed Unilateral Wilms Tumor

Probability of no relapse, secondary malignancy, or death whichever occurs first

Prevention of complete removal of at least one kidney in 50% of patients with bilateral Wilms tumor (BWT).

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 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 Bilateral Wilms Tumor (BWT) patients who undergo definitive surgery by week 12 after initiation of chemotherapy.

Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. Ineligible patients are excluded from reporting of adverse events.

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.

Dactinomycin: Given IV

Doxorubicin Hydrochloride: Given IV

Radiation Therapy: Undergo radiation therapy

Therapeutic Conventional Surgery: Undergo surgical resection

Vincristine Sulfate: Given IV

Arm 1 (Bilateral Wilms Tumors)

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.

Dactinomycin: Given IV

Doxorubicin Hydrochloride: Given IV

Radiation Therapy: Undergo radiation therapy

Therapeutic Conventional Surgery: Undergo surgical resection

Vincristine Sulfate: Given IV

Arm 2 (Unilateral High Risk Tumors Bilaterally Predisposed)

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.

Dactinomycin: Given IV

Doxorubicin Hydrochloride: Given IV

Radiation Therapy: Undergo radiation therapy

Therapeutic Conventional Surgery: Undergo surgical resection

Vincristine Sulfate: Given IV

Arm 3 (DHPLN)

All eligible BWT patients. 6 patients were excluded due to ineligibility and 6 patients were excluded due to protocol violation.

Event-Free Survival (EFS)

Eligible and evaluable Bilateral Wilms Tumor patients who completed pre-nephrectomy chemotherapy (VAD). 49 patients who did not complete VAD were excluded.

Kidney Preservation After Preoperative Chemotherapy

Eligible and evaluable patients with diffuse hyperplastic perilobar nephroblastomatosis (DPHLN).

Number of Patients Without Complete Removal of at Least One Kidney

Eligible and evaluable patients with unilateral high risk tumors who had partial or complete nephrectomy. 16 total patients were excluded (1 ineligible, 1 inevaluable, 1 violated protocol, and 13 did not have definitive surgery (partial or complete nephrectomy).

Percentage of Patients Who Experienced Partial Nephrectomy After Preoperative Chemotherapy

Eligible and evaluable Bilateral Wilms Tumor patients. 6 patients were excluded due to ineligible and 6 patients were excluded due to protocol violation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study Using Risk Factors to Determine Treatment for Children With Favorable Histology Wilms Tumors (FHWT)	NCT06401330	Stage I Kidney ... Stage II Kidney... Stage III Kidne... Stage IV Kidney...	Bone Scan Carboplatin Computed Tomogr... Cyclophosphamid... Dactinomycin Doxorubicin Etoposide Irinotecan Magnetic Resona... Nephrectomy Patient Observa... Positron Emissi... Ultrasound Imag... Vincristine X-Ray Imaging	- 30 Years	Children's Oncology Group
Vincristine, Dactinomycin, and Doxorubicin With or Without Radiation Therapy or Observation Only in Treating Younger Patients Who Are Undergoing Surgery for Newly Diagnosed Stage I, Stage II, or Stage III Wilms' Tumor	NCT00352534	Stage I Kidney ... Stage II Kidney... Stage III Kidne...	3-Dimensional C... Biospecimen Col... Chest Radiograp... Computed Tomogr... Dactinomycin Doxorubicin Hyd... Echocardiograph... Magnetic Resona... Therapeutic Con... Ultrasound Imag... Vincristine Sul...	- 29 Years	Children's Oncology Group
Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor	NCT00945009	Adult Kidney Wi... Beckwith-Wiedem... Childhood Kidne... Diffuse Hyperpl... Rhabdoid Tumor ... Stage I Kidney ... Stage II Kidney... Stage III Kidne... Stage IV Kidney... Stage V Kidney ...	Dactinomycin Doxorubicin Hyd... Radiation Thera... Therapeutic Con... Vincristine Sul...	- 29 Years	Children's Oncology Group
Gene Analysis in Studying Susceptibility to Wilms Tumor	NCT01808079	Recurrent Child... Stage I Kidney ... Stage II Kidney... Stage III Kidne... Stage IV Kidney...	Laboratory Biom...	-	Children's Oncology Group
A Study Using Risk Factors to Determine Treatment for Children With Favorable Histology Wilms Tumors (FHWT)	NCT06401330	Stage I Kidney ... Stage II Kidney... Stage III Kidne... Stage IV Kidney...	Bone Scan Carboplatin Computed Tomogr... Cyclophosphamid... Dactinomycin Doxorubicin Etoposide Irinotecan Magnetic Resona... Nephrectomy Patient Observa... Positron Emissi... Ultrasound Imag... Vincristine X-Ray Imaging	- 30 Years	Children's Oncology Group

Spots Global Cancer Trial Database for stage i kidney wilms tumor