PRIMARY OBJECTIVES:
I. To evaluate whether the addition of vincristine/irinotecan to cyclophosphamide/
carboplatin/etoposide alternating with vincristine/doxorubicin/cyclophosphamide improves the
event-free survival (EFS) of patients with newly diagnosed stage 4 diffuse anaplastic Wilms
tumor (DAWT) as compared to historical controls.
II. To evaluate whether the addition of vincristine/irinotecan to
cyclophosphamide/carboplatin/etoposide alternating with
vincristine/doxorubicin/cyclophosphamide improves the EFS of patients with standard-risk
relapsed favorable histology Wilms tumor (SRrFHWT) as compared to historical controls.
SECONDARY OBJECTIVES:
I. To evaluate whether the addition of vincristine/irinotecan to
cyclophosphamide/carboplatin/etoposide alternating with
vincristine/doxorubicin/cyclophosphamide improves the overall survival (OS) of patients with
newly diagnosed stage 4 DAWT as compared to historical controls.
II. To evaluate whether the addition of vincristine/irinotecan to
cyclophosphamide/carboplatin/etoposide alternating with
vincristine/doxorubicin/cyclophosphamide improves the OS of patients with SRrFHWT as compared
to historical controls.
III. To evaluate whether the addition of vincristine/irinotecan to
cyclophosphamide/carboplatin/etoposide alternating with
vincristine/doxorubicin/cyclophosphamide improves the EFS and OS of patients with newly
diagnosed stage 2 and 3 DAWT as compared to historical controls.
IV. To establish EFS and OS for high-risk (HRrFHWT) and very high risk (VHRrFHWT) relapsed
favorable histology Wilms tumor treated with ifosfamide/carboplatin/etoposide alternating
with cyclophosphamide/ topotecan.
EXPLORATORY OBJECTIVES:
I. To describe renal toxicity of ifosfamide/carboplatin/etoposide in HRrFHWT and VHRrFHWT
patients using conventional and novel biomarkers of renal toxicity (urine NGAL, cystatin C
and Kim1) in the context of the chemotherapy regimens used on this study.
II. To collect and bank serial blood and urine samples in patients with newly diagnosed DAWT
or relapsed FHWT and tumor tissue in patients with relapsed FHWT, for future analysis.
III. To assess the impact of p53 gene and protein expression on outcome for patients with
newly diagnosed DAWT.
IV. To determine EFS/OS in the subsets of patients with newly diagnosed DAWT or relapsed FWHT
who undergo gross total resection at all disease sites at diagnosis or after neoadjuvant
chemotherapy.
V. To describe the rate of regional lymph node sampling at the time of nephrectomy with the
use of a pre-operative surgical checklist for patients with newly diagnosed DAWT.
VI. To determine the feasibility of intensity modulated radiation therapy (IMRT) with central
quality assurance (QA) monitoring to reduce radiation induced toxicity to the heart, thyroid,
breast and solitary kidney for children with lung and liver metastases (part of an
overarching aim in this study and across frontline favorable histology Wilms tumor studies).
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM I (REGIMEN UH-3):
CYCLES 1, 5, 7, 10, AND 13: Patients receive vincristine intravenously (IV) via minibag per
institutional policy on days 1, 8, and 15. Patients also receive doxorubicin IV over 1-15
minutes and cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 21 days
during cycles 1, 5, 7, 10, and 13 in the absence of disease progression or unacceptable
toxicity.
CYCLES 2, 6, 9, 12, AND 14: Patients receive carboplatin IV over 15-60 minutes on day 1.
Patients also receive cyclophosphamide IV over 15-30 minutes and etoposide IV over 1-2 hours
on days 1-4. Treatment repeats every 21 days during cycles 2, 6, 9, 12, and 14 in the absence
of disease progression or unacceptable toxicity.
CYCLES 3, 4, 8, AND 11: Patients receive vincristine IV via minibag per institutional policy
on days 1 and 8 and irinotecan IV over 90 minutes on days 1-5. Treatment repeats every 21
days during cycles 3, 4, 8, and 11 in the absence of disease progression or unacceptable
toxicity.
Patients undergo radiation therapy (RT) at week 7 of cycle 3 as clinically indicated.
Patients undergo a computed tomography (CT) scan, a positron emission tomography (PET) scan,
a chest x-ray, magnetic resonance imaging (MRI), an abdominal ultrasound, and/or a bone scan
throughout the trial. Patients may also undergo blood specimen collection and biopsy
throughout the trial.
ARM II (REGIMEN IFOSFAMIDE, CARBOPLATIN, ETOPOSIDE [ICE]/CYCLOPHOSPHAMIDE [CYCLO]/TOPOTECAN
[TOPO]):
CYCLES 1, 2, 4, 5, 7, AND 9: Patients receive carboplatin IV over 15-60 minutes on day 1.
Patients also receive etoposide IV over 1-2 hours and ifosfamide IV over 2-4 hours on days
1-3. Treatment repeats every 21 days during cycles 1, 2, 4, 5, 7, and 9 in the absence of
disease progression or unacceptable toxicity.
CYCLES 3, 6, 8, AND 10: Patients receive cyclophosphamide IV over 15-30 minutes and topotecan
IV over 30 minutes on days 1-5. Treatment repeats every 21 days during cycles 3, 6, 8, and 10
in the absence of disease progression or unacceptable toxicity.
Patients undergo surgery and/or RT during cycles 4, 7, and 10 as clinically indicated.
Patients undergo a CT scan, a PET scan, a chest x-ray, MRI, an abdominal ultrasound, and/or a
bone scan throughout the trial. Patients may also undergo blood specimen collection and
biopsy throughout the trial.
After completion of study treatment, patients are followed up every 3 months for years 1-2,
every 6 months for years 3-4, and once at year 5.