AREN0321, Treatment of High Risk Renal Tumors

Summary

Enrollment on AREN03B2 Renal Tumors Classification, Biology, and Banking Study (STU 092010-004) is required prior to enrollment on AREN0321. Consent for study enrollment must be obtained before any AREN0321 protocol therapy is given.

Four treatment regimens or surgery only, will be applied according to tumor histology, stage, and response to treatment. Most patients will have had surgical resection before beginning chemotherapy, as outlined in the AREN03B2 study. Patients with initially unresectable or incompletely resected tumors will receive chemotherapy and undergo imaging reevaluation after 4 cycles (approximately 12 weeks). If the tumor is deemed resectable at Week 13, surgery will be performed.


* Regimen DD-4A: vincristine/dactinomycin/doxorubicin x 25 weeks; XRT

* Revised Regimen UH-1: cyclophosphamide/carboplatin/etoposide; vincristine/ doxorubicin/ cyclophosphamide; x 30 weeks; XRT

* Vincristine/irinotecan Window Therapy: Revised Regimen UH-1 and Revised Regimen UH-2 (Revised Regimen UH-2: cyclophosphamide/carboplatin/etoposide; vincristine/ doxorubicin/ cyclophosphamide; vincristine/irinotecan x 36 weeks; XRT). Patients eligible for Window Therapy may refuse Window Therapy and may be enrolled on Revised Regimen UH-1.

* Regimen I: vincristine/doxorubicin/cyclophosphamide; cyclophosphamide/etoposide x 25 weeks; XRT (No XRT for Stage 1 CCSK.)

* Observation arm: Patients entering this arm of the study will have had surgery before enrolling. Our plan is to watch the subject carefully to see if there is any sign that the tumor has come back. The subject will have follow-up exams and scans for about five years.

Subjects in this clinical trial are expected to receive treatment for up to 8 months, depending on their treatment regimen. After treatment, subjects will have follow-up examinations and medical tests for about five years. In addition, we plan to collect some medical information about how the subject is doing for about five years after the study closes to patient enrollment.

Participant Eligibility

Consent for study enrollment must be obtained before any AREN0321 protocol therapy is given.

1) Patients must be < 30 years old at the time of initial diagnosis.
2) Patients with newly diagnosed disease of one of the following histological types (Stages I-IV):
• Focal Anaplastic Wilms Tumor
• Diffuse Anaplastic Wilms Tumor
• Clear Cell Sarcoma of Kidney
• Malignant Rhabdoid Tumor (Renal or extra renal, excluding CNS tumors)
• Renal Cell Carcinoma (clear cell, papillary, renal medullary, oncocytoid, sarcomatoid, chromophobe, translocation, collecting duct, carcinoma associated with neuroblastoma, renal cell carcinoma unclassified)

Enrollment on AREN03B2 Renal Tumors Classification, Biology, and Banking Study (STU 092010-004) is required prior to enrollment on AREN0321.

3) The Karnofsky performance status must be ≥ 50 for patients >16 years of age and the Lansky performance status must be ≥ 50 for patients ≤ 16 years of age.
4) Patients must not have received systemic chemotherapy or radiation therapy prior to treatment on this study UNLESS they were enrolled on the AREN0532 or AREN0533 studies and received pre-nephrectomy chemotherapy for what was originally presumed to be favorable histology Wilms tumor.
5) Adequate liver function defined as:
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, and
- SGOT (AST) or SGPT (ALT) < 2.5 x upper limit of normal (ULN) for age.

6) Adequate cardiac function defined as:
- Shortening fraction of ≥ 27% by echocardiogram, or
- Ejection fraction of ≥ 50% by radionuclide angiogram.

7) Female patients of childbearing age must have a negative pregnancy test.
8) Female patients who are lactating must agree to stop breastfeeding.
9) Sexually active patients of childbearing potential must agree to use effective contraception.
10) All patients and/or their parents or legal guardians must sign a written informed consent.
11) All institutional, FDA, and NCI requirements for human studies must be met.