This phase II trial studies how well combination chemotherapy works in treating patients with newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT) or favorable histology Wilms tumors (FHWT) that have come back (relapsed). Drugs used in chemotherapy regimens such as UH-3 (vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan) and ICE/Cyclo/Topo (ifosfamide, carboplatin, etoposide, cyclophosphamide, and topotecan) 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. This trial may help doctors find out what effects, good and/or bad, regimen UH-3 has on patients with newly diagnosed DAWT and standard risk relapsed FHWT (those treated with only 2 drugs for the initial WT) and regimen ICE/Cyclo/Topo has on patients with high and very high risk relapsed FHWT (those treated with 3 or more drugs for the initial WT).
Patients with newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on APEC14B1, consented to Part A - Eligibility Screening, and have received an initial stratum assignment showing DAWT (if anaplasia first identified at diagnostic, pre-treatment nephrectomy or biopsy) or a final stratum assignment showing DAWT (if anaplasia first noted at delayed nephrectomy) prior to enrollment on AREN1921. Prior enrollment on APEC14B1 is not an eligibility requirement for patients with relapsed favorable histology Wilms tumor.
Patients must be =< 30 years old at study enrollment
Newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor as confirmed by central review
Standard-Risk relapse: Patients who received two chemotherapy agents for frontline therapy; primarily actinomycin D and vincristine
Patients with a history of bilateral Wilms tumor (synchronous or metachronous)
Patients with any uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, or symptomatic congestive heart failure (defined as grade 2 or higher heart failure per Common Terminology Criteria for Adverse Events [CTCAE] version 5.0)
Relapsed FHWT patients who did not receive frontline chemotherapy (e.g., very low risk FHWT initially observed without chemotherapy) or received only one chemotherapy agent for frontline therapy
Patients with renal tubular acidosis (RTA) as evidenced by serum bicarbonate < 16 mmol/L and serum phosphate =< 2 mg/dL (or < 0.8 mmol/L) without supplementation
Parallel
Biopsy Procedure
Procedure/SurgeryUndergo a biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Scan
Procedure/SurgeryUndergo a bone scan
Carboplatin
DrugGiven IV
Computed Tomography
Procedure/SurgeryUndergo a CT scan
Cyclophosphamide
DrugGiven IV
Doxorubicin
DrugGiven IV
Etoposide
DrugGiven IV
Ifosfamide
DrugGiven IV
Irinotecan
DrugGiven IV
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Positron Emission Tomography
Procedure/SurgeryUndergo a PET scan
Radiation Therapy
RadiationUndergo RT
Surgical Procedure
Procedure/SurgeryUndergo surgery
Topotecan
DrugGiven IV
Transabdominal Ultrasound
Procedure/SurgeryUndergo abdominal ultrasound
Vincristine
DrugGiven IV
X-Ray Imaging
Procedure/SurgeryUndergo a chest x-ray
Event-free survival (EFS) for stratum 1-3
Kaplan-Meier method will be used to estimate EFS, defined as the time from study entry until relapse or disease progression, secondary malignancy, or death.
EFS for stratum 4
Kaplan-Meier method will be used to estimate 4-year EFS, defined as the time from study entry until relapse or disease progression, secondary malignancy, or death.
Overall survival (OS) for stratum 1-4
The Kaplan-Meier method will be used to estimate OS, defined as the time from study entry until death.
Percentage of patients experiencing grade 3+ renal adverse events
Percentage of patients experiencing grade 3 or higher renal adverse events. Will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Collection of blood and urine samples
For all Strata 1-4, serial blood and urine samples will be collected (during protocol therapy, at the end of protocol therapy, and at first relapse) and banked for future analysis such as evaluation of minimal residual disease by assessing levels of circulating tumor-derived deoxyribonucleic acid (ctDNA).
p53 biomarker analysis
For patients with diffuse anaplastic Wilms tumors (DAWT) (Strata 1 and 2), p53 from diagnostic tissue will be assessed, and rates of p53 mutations described overall and within each stratum. Degree of anaplasia as a predictor of p53 mutation status will be analyzed in logistic regression models, and association of p53 status with EFS and OS will be analyzed in Cox regression models, stratified by disease stage. Possible interactions between p53 mutation status and degree of anaplasia in outcome models will be explored.
EFS for patients with gross total disease resection
EFS will be described for newly diagnosed disease stage 2-4 DAWT patients (Strata 1 and 2) and relapsed favorable histology Wilms tumors (FHWT) patients (Strata 3 and 4) who have gross total disease resection prior to enrollment or at the time of delayed nephrectomy following adjuvant chemotherapy. Kaplan-Meier curves will be reported by strata with 95% confidence bands. Potential prognostic factors for these patients will be explored in Cox regression models.
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Children's Oncology Group
Lead sponsor
National Cancer Institute (NCI)
Collaborator