Title
Treatment of Newly Diagnosed Diffuse Anaplastic Wilms Tumors (DAWT) and Relapsed Favorable Histology Wilms Tumors (FHWT)

Description
Phase II Treatment of Newly Diagnosed Diffuse Anaplastic Wilms Tumors (DAWT) and Relapsed Favorable Histology Wilms Tumors (FHWT)

Objective

The overall goal of this study is to find out what effects, good and/or bad, Regimen ICE/Cyclo/Topo has on people with high-risk or very high-risk relapsed FHWT

The overall goal of this study is to find out what effects, good and/or bad, Regimen UH-3 has on people with standard-risk relapsed FHWT

Treatment
Patients diagnosed with Stages 2-4 diffuse anaplastic Wilms tumor and Standard-Risk relapsed favorable histology Wilms tumor will receive Regimen UH-3

Vincristine/Doxorubicin/Cyclophosphamide (VDCy) Cycles 1, 5, 7, 10 and 13, Cyclophosphamide/Carboplatin/Etoposide (CCE) Cycles 2, 6, 9, 12, and 14, Vincristine/Irinotecan (VI)
Cycles 3, 4, 8, and 11. Radiation therapy will be given at the same time Cycle 3 begins

Patients who are diagnosed with High-Risk relapsed favorable histology Wilms tumor and Very High-Risk relapsed favorable histology Wilms tumor will receive Regimen ICE/Cyclo/Topo

Ifosfamide/Carboplatin/Etoposide (ICE) Cycles 1, 2, 4*, 5, 7*, and 9. *Surgery and/or radiation therapy will be considered during these cycles. Cyclophosphamide/Topotecan (CPM/TOPO)
Cycles 3, 6, 8, and 10* *Surgery and/or radiation therapy will be considered during this cycle

Key Eligibility
Patients with newly diagnosed Stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on AREN03B2 and have risk assignment or final pathology classification (if at delayed nephrectomy) results available prior to enrollment on AREN1921. Enrollment on AREN03B2 is not applicable for patients with relapsed favorable histology Wilms tumor

Must be less than or equal to 30 years of age

ECOG 0-2. Karnofsky if less than 16 years of age and Larnsky if greater than or equal to 16 years of age

Newly diagnosed DAWT who undergo upfront nephrectomy must have at least 1 lymph node sampled prior to study enrollment

Newly diagnosed Stages 2 – 4 diffuse anaplastic Wilms tumor must be enrolled on AREN1921 within 2 weeks of the first tumor-directed surgery or biopsy procedure (surgery/biopsy is Day 0), except for patients who received prior therapy for presumed favorable histology Wilms tumor, later confirmed to have diffuse anaplastic Wilms tumor at subsequent review as defined by the protocol

Newly diagnosed Stages 2 - 4 diffuse anaplastic Wilms tumor as confirmed by central review

Favorable histology Wilms tumor at first relapse. Relapsed FHWT patients must have previously achieved remission for their initial FHWT diagnosis to be eligible for this study. The relapse risk groups are defined as follows,
regardless of radiation therapy: Standard-Risk relapse: Patients who received two chemotherapy agents for frontline therapy; primarily actinomycin D and vincristine. High-Risk relapse: Patients who received three chemotherapy agents for frontline therapy; primarily vincristine, actinomycin D and doxorubicin or vincristine, actinomycin D and irinotecan. Very High-Risk relapse: Patients who received four or more chemotherapy agents as part of initial therapy; primarily Regimen M or its variations

Newly diagnosed DAWT must have had histologic verification of the malignancy. For relapsed FHWT patients, biopsy to prove recurrence is encouraged, but not required

Adequate Bone Marrow, Renal, Liver, and Cardiac function as defined by the protocol

Diffuse Anaplastic Wilms Tumor, must have had no prior systemic therapy except in situations defined by the protocol

Patients who received prior therapy for presumed favorable histology Wilms tumor, later identified to have diffuse anaplastic Wilms tumor as per above, must begin study treatment starting at Cycle 3 (Week 7) of Regimen UH-3

Patients who received emergency radiation to preserve organ function are eligible

Relapsed Favorable Histology Wilms Tumor. Patients must not have received prior chemotherapy for their relapsed favorable histology Wilms tumor diagnosis

EXCLUSION

History of bilateral Wilms tumor (synchronous or metachronous)

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 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

For patients with high-risk or very high-risk relapsed FHWT: Patients with Renal Tubular Acidosis (RTA) as evidenced by serum bicarbonate less than 16 mmol/L and serum phosphate less than or equal to 2 mg/dL (or less than 0.8 mmol/L) without supplementation

Stages 2-4 DAWT and standard-risk relapsed FHWT patients: Chronic inflammatory bowel disease and/or bowel obstruction. Concomitant use of St. John’s wort, which cannot be stopped prior to the start of trial treatment

Can not be pregnant or breastfeeding. Male and Female of childbearing potential must agree to adequate birth control as defined by the protocol

Applicable Disease Sites
Kidney

Participating Institutions
Gundersen Health System; UW Health University Hospital