IRB Number:

07-000221

Trial Status:

Open for Enrollment

Phase: II

Why is this study being done?

This is a study for children and young adults with high-risk cancers that usually start in the kidney. The study was designed for patients with anaplastic Wilms tumor, malignant rhabdoid tumor, clear cell sarcoma of the kidney, and renal cell carcinoma. These tumors are called "high-risk" tumors because they are likely to spread to other areas of the body and/or come back during or after treatment. The high-risk kidney tumors are very rare; only about 50 children and young adults are diagnosed with a high-risk kidney tumor each year in North America. This study has different treatment "arms" that vary according to the stage and type of the tumor.

Who is Eligible to Participate in the Study?

-Age 30 or younger
-No prior systemic chemotherapy or radiation therapy
-Newly diagnosed disease of one of the following types:
- Focal anaplastic Wilms tumor (FAWT)
- Diffuse anaplastic Wilms tumor (DAWT)
- Clear cell sarcoma of the kidney (CCSK)
- Malignant rhabdoid tumor (renal or extrarenal) (MRT)
- Renal cell carcinoma (RCC)

*More specific, detailed eligibility and/ or exclusion criteria are associated with this trial.

What is Involved With this Study?

Patients are assigned to one of six treatment regimens according to tumor type, stage of disease, and response to treatment.

- Surgery (renal cell carcinoma [RCC]): Patients with completely resectable stage I-IV RCC undergo surgical resection. Patients with incompletely resectable stage IV RCC undergo treatment as per physician's choice.

- Regimen UH-1 (stage II-III or stage IV [with no measurable disease] diffuse anaplastic Wilms tumor [DAWT], stage I-II or stage III-IV [with no measurable disease] malignant rhabdoid tumor [MRT], stage IV focal anaplastic Wilms tumor [FAWT], or stage IV clear cell sarcoma of the kidney [CCSK]): Patients receive vincristine IV on day 1 in weeks 1-3, 10-15, 22-24, and 28-30; doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 and cyclophosphamide (CPM1) IV over one hour on day 1 in weeks 1, 10, 13, 22, and 28; and cyclophosphamide (at lower doses [CPM5]) IV over 1 hour and etoposide IV over one hour on days 1-5 and carboplatin IV over 1 hour on day 1 in weeks 4, 7, 16, 19, and 25. Patients also receive filgrastim (G-CSF) subcutaneously or IV once daily beginning 24 hours after completion of chemotherapy and continuing until blood counts recover.

Patients whose primary tumors were initially resected undergo radiotherapy once daily five days a week for four to five and one half weeks beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13. Patients with unresectable CCSK receive no further study therapy.

- Irinotecan/vincristine window therapy* (stage IV DAWT with measurable disease at diagnosis OR any stage unresectable MRT): Patients receive vincristine IV on days 1 and 8 and irinotecan hydrochloride IV over 30 minutes on days 1-5 and 8-12 (course 1). Patients with progressive disease (PD) are treated with regimen UH-1. Patients with stable disease (SD), partial response (PR), or complete response (CR) receive another course of irinotecan hydrochloride/vincristine window therapy beginning on day 22. After the second course, patients with SD or PD are treated with regimen UH-1 and patients with PR or CR are treated with regimen UH-2.
NOTE: *Patients who are eligible for but who are unwilling to receive window therapy, receive therapy on regimen UH-1.

- Regimen UH-2 (DAWT or MRT with CR/PR to irinotecan hydrochloride/vincristine window therapy): Patients receive vincristine on day 1 in weeks 1-3, 10, 11, 16-21, 25, 26, 28-30, and 34-36 and doxorubicin hydrochloride and CPM1 as in regimen UH-1 in weeks 1, 16, 19, 28, and 34. Patients also receive CPM5, etoposide, and carboplatin as in regimen UH-1 in weeks 4, 7, 13, 22, and 31 and irinotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 10, 11, 25, and 26. Patients also receive G-CSF as in regimen UH-1. Patients whose primary tumors were initially resected undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 7. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 7.

- Regimen I (stage I-III CCSK): Patients receive vincristine IV on day 1 in weeks 1-3, 5-9, 11-14, 19, and 25; doxorubicin hydrochloride IV over 15 minutes on day 1 and cyclophosphamide IV over 1 hour on days 1-3 in weeks 1, 7, 13, 19, and 25; and CPM5 and etoposide as in regimen UH-1 in weeks 4, 10, 16, and 22. Patients also receive G-CSF as in regimen UH-1. Patients whose primary tumors were initially resected (except those with stage I CCSK) undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13.
- Regimen DD-4A (stage I DAWT or stages I-III FAWT): Patients receive dactinomycin IV over one to five minutes on day 1 in weeks 1, 7, 13, 19, and 25; vincristine IV on day 1 in weeks 1-10, 13, 16, 19, 22, and 25; and doxorubicin hydrochloride IV over 15 minutes on day 1 in weeks 4, 10, 16, and 22. Patients whose primary tumors were initially resected undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13.

Treatment continues in the absence of disease progression or unacceptable side effects.

How long will the Study run?

The research staff would like the patient to have follow-up exams and scans for about five years as part of their regular medical care. Then, the researchers would like to continue to collect some medical information about how the patient is doing for about five years after the study closes to patient enrollment. Keeping in touch with the patient and checking on how their health is every year for a while after the study closes helps the research staff understand the long-term effects of the study.

Sponsor(s): Children's Oncology Group (COG)

Study Activation/Registration Date: 05/01/2007

IRB Review and Approval Date: 04/23/2007

Study Type: Treatment

Projected Accrual: The plan is to have up to 295 patients participate from multiple medical centers; with 25 from Mayo Clinic.

Costs of Study:There may be standard patient care costs related to participating in a cancer research study.

Principal Investigator: Shakila P. Khan, MD

Who can I Contact for Additional Information on this Trial?

Complete Request Form for Cancer Clinical Trial Information at Mayo Clinic or
For more information about this study or other clinical trial options, please contact our Mayo Clinic Cancer Center Clinical Trials Referral Office.

• Patients living within the United States, call 507-538-7623, or e-mail cancerclinicaltrials@mayo.edu


• Patients living outside the United States may call our International Office at 507-284-8884, or e-mail intl.mcr@mayo.edu.

What is/are the Locations of this Clinical Trial?

• Rochester, MN

Last updated: 05/23/2008