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

REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV. Patients with pulmonary and extra-pulmonary metastases at diagnosis undergo radiotherapy.

Patients with initially unresectable or incompletely resected tumors are reevaluated at week 6, and if resectable, undergo surgery and then proceed to either regimen DD4A or regimen M.

REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV.

REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV; vincristine IV; and dactinomycin IV and doxorubicin hydrochloride IV. Patients with pulmonary metastases only who are SIR also undergo whole lung radiotherapy.

3-Dimensional Conformal Radiation Therapy

Conventional Surgery

Doxorubicin Hydrochloride

Vincristine Sulfate Liposome

David B Dix

This phase III trial is studying how well combination chemotherapy with or without radiation therapy works in treating young patients with newly diagnosed stage III or stage IV Wilms' tumor. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving more than one drug (combination chemotherapy) with or without radiation therapy may kill more tumor cells.

PRIMARY OBJECTIVES:

I. Determine the 4-year event-free survival (EFS) of patients with stage IV favorable histology (FH) Wilms' tumor with pulmonary metastases only who have complete resolution of pulmonary lesions without whole lung irradiation treated with DD4A chemotherapy comprising vincristine, dactinomycin, and doxorubicin hydrochloride.

II. Determine the 4-year EFS of these patients who do not have resolution of pulmonary metastases by week 6 treated with the addition of cyclophosphamide and etoposide to a modified-regimen DD4A (regimen M).

III. Determine the 4-year EFS of patients with stage III or IV FH Wilms' tumor with loss of heterozygosity for chromosomes 1p and 16q treated with regimen M.

SECONDARY OBJECTIVES:

I. Correlate the burden of pulmonary metastatic disease with outcome in patients with stage IV FH Wilms' tumor.

OUTLINE: This is a multicenter study.

REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV over 1-5 minutes once in week 1; vincristine IV once in weeks 1-6; and doxorubicin hydrochloride IV over 15 minutes once in week 4 in the absence of disease progression or unacceptable toxicity. Patients with pulmonary and extra-pulmonary metastases at diagnosis undergo radiotherapy once daily beginning in week 1 and continuing for 5-14 days. After completion of DD4A chemotherapy (week 6), patients undergo evaluation. Patients with stage IV disease and pulmonary metastases only with no loss of heterozygosity (LOH) who are rapid complete responders (RCR) (i.e., pulmonary metastases disappear) proceed to regimen DD4A (weeks 7-25).

All other patients (i.e., patients with stage III or IV disease and LOH of both 1p and 16q; stage IV disease with pulmonary metastases only who are slow incomplete responders \[SIR\] \[i.e., pulmonary metastases do not disappear\]; or stage IV disease with nonpulmonary metastases or with nonpulmonary metastases in combination with pulmonary metastases) proceed to regimen M (weeks 7-31).

Patients with initially unresectable or incompletely resected tumors are reevaluated at week 6, and if resectable, undergo surgery and then proceed to either regimen DD4A or regimen M as described above.

REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV over 1-5 minutes once in weeks 7, 13, 19, and 25; vincristine IV once in weeks 7-10, 13, 16, 19, 22, and 25; and doxorubicin hydrochloride IV over 15 minutes once in weeks 10, 16, and 22 in the absence of disease progression or unacceptable toxicity.

REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 7, 10, 19, and 25; vincristine IV once in weeks 8, 9, 11, 12, 13, 16, 22, 28, and 31; and dactinomycin IV and doxorubicin hydrochloride IV over 15 minutes once in weeks 13, 16, 22, 28, and 31 in the absence of disease progression or unacceptable toxicity. Patients with pulmonary metastases only who are SIR also undergo whole lung radiotherapy once daily beginning in week 7 and continuing for 5-14 days.

NOTE: Patients who begin study treatment after undergoing resection of pulmonary metastases are treated according to regimen DD4A (weeks 1-25) and undergo whole lung radiotherapy for 5-14 days beginning in week 1.

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

Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed Stage III or Stage IV Wilms' Tumor

Treatment of Newly Diagnosed Higher Risk Favorable Histology Wilms Tumors

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

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

National Cancer Institute (NCI)

Stage IV and rapid complete response (RCR) of lung metastases continuously treated with DD4A after 6 weeks of DD4A.

Stage IV and Rapid Complete Response (RCR) of Lung Metastases

Stage IV and slow incomplete response (SIR) of lung metastases treated with Regimen M after 6 weeks of DD4A.

Stage IV and Slow Incomplete Response (SIR) of Lung Metastases

Stage III/IV with LOH 1p and 16q treated with Regimen M.

Stage III/IV With LOH 1p and 16q Treated With Regimen M

Stage IV with non-lung disease treated with Regimen M.

Stage IV With Non-lung Disease Treated With Regimen M

Stage IV with lung metastases treated with DD4A for less than 6 weeks and/or response inevaluable at week 6.

Stage IV With Lung Metastases

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Results Reporting Coordinator

Event Free Survival Probability

Stage IV and slow incomplete response (SIR) of lung metastases treated with Regimen M after 6 weeks of DD4A

doxorubicin hydrochloride: Given IV

liposomal vincristine sulfate: Given IV

conventional surgery

3-dimensional conformal radiation therapy

dactinomycin: Given IV

cyclophosphamide: Given IV

etoposide: Given IV

Analysis includes only eligible patients.

Event Free Survival (EFS) Probability

Stage III/IV with LOH 1p and 16q treated with Regimen M

doxorubicin hydrochloride: Given IV

liposomal vincristine sulfate: Given IV

conventional surgery

3-dimensional conformal radiation therapy

dactinomycin: Given IV

cyclophosphamide: Given IV

etoposide: Given IV

Stage IV with non-lung disease treated with Regimen M

doxorubicin hydrochloride: Given IV

liposomal vincristine sulfate: Given IV

conventional surgery

dactinomycin: Given IV

cyclophosphamide: Given IV

etoposide: Given IV

All eligible patients were included in this analysis.

Lung Mets <= 1cm

Lung Mets > 1cm

Analysis population is eligible stage (stg) IV patients (pts) with lung mets only. On Participant Flow table, these pts include 120 RCR, 135 SIR, 21 stg IV with LOH (of 52 when including stg III), and 23 stg IV with lung mets (off therapy before week 6). A total of 299 stg IV pts, exceeding the total number of participant (297) analyzed for OM 4.

Event Free Survival Associated With the Burden of Pulmonary Metastatic Disease

Overall Study

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

Therapeutic Conventional Surgery

Vincristine Sulfate

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.

Percentage of Patients Who Had Definitive Surgical Treatment

Recurrence

Disease Susceptibility

Samples are analyzed for SNP profiling using real-time PCR and MLPA.

Laboratory Biomarker Analysis

Paul Grundy

This clinical trial studies gene analysis in studying susceptibility to Wilms tumor. Finding genetic markers for Wilms tumor may help identify patients who are at risk of relapse.

PRIMARY OBJECTIVES:

I. To use a genome-wide association analysis to identify novel genetic variants that confer susceptibility to Wilms tumor.

II. To improve our understanding of the genetic architecture and etiology of Wilms tumor.

III. To facilitate the identification of genetic markers that are associated with an increased risk of developing of Wilms tumor and/or those at risk of aggressive disease, relapse, additional tumors and/or cancer in their offspring.

OUTLINE:

Samples are analyzed for single nucleotide polymorphism (SNP) profiling using real-time polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA).

Gene Analysis in Studying Susceptibility to Wilms Tumor

A Genome-Wide Association Study in Wilms Tumor

Compared using the Cochran Armitage trend test (1-df). The data will be analyzed individually for the UK/US study populations and combined using a Mantel-Haenszel analysis adjusting for study group, and related methods which allow for different effects in each population (for confirmed loci, we will compare effects across populations).

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
Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed Stage III or Stage IV Wilms' Tumor	NCT00379340	Stage III Kidne... Stage IV Kidney...	3-Dimensional C... Conventional Su... Cyclophosphamid... Dactinomycin Doxorubicin Hyd... Etoposide Vincristine Sul...	- 29 Years	Children's Oncology Group
Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed Stage III or Stage IV Wilms' Tumor	NCT00379340	Stage III Kidne... Stage IV Kidney...	3-Dimensional C... Conventional Su... Cyclophosphamid... Dactinomycin Doxorubicin Hyd... Etoposide 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 iv kidney wilms tumor