Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Diseases and Abnormalities at or Before Birth

Symptoms and General Pathology

Rare Diseases

Carcinoma, Renal Cell

Wilms Tumor

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Neoplasms by Histologic Type

Syndrome

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Renal Cell Carcinoma

Wilms' Tumor

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Carboplatin

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Vincristine

Dactinomycin

Etoposide phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Tubulin Modulators

Antimitotic Agents

dactinomycin

carboplatin

cyclophosphamide

doxorubicin hydrochloride

etoposide

vincristine sulfate

adjuvant therapy

conventional surgery

neoadjuvant therapy

radiation therapy

Francois Pein, MD

Norbert Graf

Jan DeKraker, MD

Kathy Pritchard-Jones, MD

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy before surgery may shrink the tumor so it can be removed during surgery. Giving more chemotherapy after surgery may kill any remaining tumor cells. It is not yet known which chemotherapy regimen after surgery is most effective in treating Wilm's tumor.

PURPOSE: Phase III trial to study the effectiveness of chemotherapy before and after surgery in treating children who have Wilm's tumor.

OBJECTIVES:

* Determine the response rate in children with Wilms' tumor treated with pre-operative chemotherapy.
* Compare the response rate in children with intermediate-risk stage II or III Wilms' tumor treated with or without doxorubicin after surgery.
* Determine the prognostic significance of histological subtypes in these patients after pre-operative chemotherapy.
* Determine whether reduced treatment minimizes acute and late toxicity without jeopardizing event-free and overall survival in patients with focal anaplasia or intermediate-risk stage I Wilms' tumor.
* Determine the prognostic significance of tumor volume and specimen weight after pre-operative chemotherapy and its relation to histological subtype in these patients.
* Determine the effect of single-dose dactinomycin as pre-operative chemotherapy in these patients.
* Correlate allele loss at 16q, 1p, and other chromosomal regions with relapse-free and overall survival of patients treated with these regimens.
* Correlate allele losses with clinical risk factors (e.g., histological appearance and tumor volume) after pre-operative chemotherapy in these patients.
* Determine laboratory indicators of myocardial damage in patients treated with these regimens.
* Determine the prognostic significance of the percentage of necrosis after pre-operative chemotherapy, in terms of type and amount of residual viable tumor, in these patients.

OUTLINE: This is a partially randomized, multicenter study. Patients are stratified according to country and participating center. Patients with intermediate-risk stage II or III disease are further stratified according to histology (blastemal vs epithelial vs stromal vs mixed).

Patients with localized disease receive neoadjuvant therapy comprising vincristine IV on days 1, 8, 15, and 22 and dactinomycin IV on days 1 and 15.

Patients undergo surgery during weeks 5 or 6.

Patients with low-risk stage I disease receive no further therapy.

Adjuvant chemotherapy begins after surgery and within 21 days of last dose of neoadjuvant chemotherapy.

Patients with intermediate-risk stage I disease receive vincristine IV on days 1, 8, 15, and 22 and dactinomycin IV on day 7.

Patients with intermediate-risk stage II or III disease are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive vincristine IV weekly for 8 weeks and then on days 1 and 7 of weeks 11, 14, 17, 20, 23, and 26. Patients also receive dactinomycin IV weekly on weeks 2, 5, 8, 11, 14, 17, 20, 23, and 26 and doxorubicin IV over 4-6 hours weekly on weeks 2, 8, 14, 20, and 26.
* Arm II: Patients receive vincristine and dactinomycin as in arm I. Patients with high-risk stage I disease receive chemotherapy as in arm I. Patients with low-risk stage II disease receive chemotherapy as in arm II.

Patients with high-risk stage II or III disease receive cyclophosphamide IV over 1 hour on days 1-3 and doxorubicin IV over 4-6 hours on day 1 on weeks 1, 7, 13, 19, 25, and 31. Patients also receive etoposide IV over 4 hours and carboplatin IV over 1 hour on days 1-3 on weeks 4, 10, 16, 22, 28, and 34.

Patients with intermediate-risk stage III or high-risk stage II or III disease also undergo radiotherapy for approximately 3 weeks during chemotherapy.

Patients with metastatic disease receive neoadjuvant chemotherapy comprising vincristine IV on day 1 of weeks 1-6, dactinomycin IV on day 1 of weeks 1, 3, and 5, and doxorubicin IV over 4-6 hours on day 1 of weeks 1 and 5.

Patients undergo surgery during week 7.

Within 2 weeks of surgery patients receive 1 of the following adjuvant chemotherapy regimens:

* Regimen A (no metastases or completely resected): Patients receive vincristine IV weekly for 8 weeks and then on weeks 11, 12, 14, 15, 17, 18, 20, 21, 23, 24, 26, and 27. Patients also receive dactinomycin IV on day 1 of weeks 2, 5, 8, 11, 14, 17, 20, 23, and 26 and doxorubicin IV over 4-6 hours on weeks 2, 8, 14, and 20. Some patients also undergo radiotherapy concurrently with chemotherapy for approximately 3 weeks.
* Regimen B (multiple inoperable metastases, incomplete resection, or high-risk primary disease): Patients receive etoposide IV over 4 hours and carboplatin IV over 1 hour on days 1-3 of weeks 4, 10, 13, 16, 22, 25, 28, and 34. Patients also receive cyclophosphamide IV over 1 hour on days 1-3 and doxorubicin IV over 4-6 hours on day 1 of weeks 1, 7, 19, and 31. Some patients also undergo radiotherapy concurrently with chemotherapy for approximately 3 weeks.

Patients are followed every 2-3 months for 2 years, every 3-6 months for 1-2 years, and then every 6-12 months thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 350 patients (174 per treatment arm) will be accrued for the randomized portion of this study within 7 years.

Chemotherapy Before and After Surgery in Treating Children With Wilm's Tumor

Nephroblastoma (Wilms Tumour) Clinical Trial And Study

Societe Francaise Oncologie Pediatrique

Children's Cancer and Leukaemia Group

German Society for Pediatric Oncology and Hematology GPOH gGmbH

University of Leicester

Digestive System Diseases

Nervous System Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Neuroblastoma

Sarcoma

Liver Neoplasms

Central Nervous System Neoplasms

Medulloblastoma

Nervous System Neoplasms

Rhabdomyosarcoma

Hepatoblastoma

Pulmonary Blastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Soft Tissue Sarcoma

Medulloblastoma, Childhood

Pleuropulmonary Blastoma

Neuroepithelioma

DNA analysis

cytogenetic analysis

gene expression analysis

gene rearrangement analysis

mutation analysis

polymerase chain reaction

polymorphism analysis

laboratory biomarker analysis

medical chart review

Dana A. Hill, MD

RATIONALE: The identification of gene mutations in young patients with pleuropulmonary blastoma syndrome may allow doctors to better understand the genetic processes involved in the development of some types of cancer, and may also help doctors identify patients who are at risk for cancer.

PURPOSE: This research study studies gene mutations in samples from young patients with pleuropulmonary blastoma syndrome at risk for developing cancer.

OBJECTIVES:

* To determine if DICER1 mutations contribute to tumor pathogenesis in cystic nephromas and cystic partially differentiated nephroblastomas outside of families with pleuropulmonary blastoma (PPB) syndrome.

OUTLINE: Archived DNA samples are analyzed for DICER1 mutation by qPCR and directly sequenced using BigDye Terminator chemistry. Results are then compared against the single nucleotide polymorphism (SNP) database.

Gene Mutation in Samples From Young Patients With Pleuropulmonary Blastoma Syndrome at Risk for Developing Cancer

Investigation of DICER1 in Cystic Nephroma and Cystic Partially Differentiated Nephroblastoma

National Cancer Institute (NCI)

Children's Oncology Group

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Chemotherapy Before and After Surgery in Treating Children With Wilm's Tumor	NCT00047138	Kidney Cancer	dactinomycin carboplatin cyclophosphamid... doxorubicin hyd... etoposide vincristine sul... adjuvant therap... conventional su... neoadjuvant the... radiation thera...	- 18 Years	National Cancer Institute (NCI)
Chemotherapy Before and After Surgery in Treating Children With Wilm's Tumor	NCT00047138	Kidney Cancer	dactinomycin carboplatin cyclophosphamid... doxorubicin hyd... etoposide vincristine sul... adjuvant therap... conventional su... neoadjuvant the... radiation thera...	- 18 Years	National Cancer Institute (NCI)
Gene Mutation in Samples From Young Patients With Pleuropulmonary Blastoma Syndrome at Risk for Developing Cancer	NCT01353300	Brain and Centr... Hereditary Wilm... Kidney Cancer Liver Cancer Neuroblastoma Pleuropulmonary... Sarcoma	DNA analysis cytogenetic ana... gene expression... gene rearrangem... mutation analys... polymerase chai... polymorphism an... laboratory biom... medical chart r...	- 120 Years	Children's Oncology Group

Spots Global Cancer Trial Database for stromal predominant wilms tumor