A Study Using Risk Factors to Determine Treatment for Children With Favorable Histology Wilms Tumors (FHWT)
Protocol Description
This phase III trial studies using risk factors in determining treatment for children with favorable tissue (histology) Wilms tumors (FHWT). Wilms Tumor is the most common type of kidney cancer in children, and FHWT is the most common subtype. Previous large clinical trials have established treatment plans that are likely to cure most children with FHWT, however some children still have their cancer come back (called relapse) and not all survive. Previous research has identified features of FHWT that are associated with higher or lower risks of relapse. The term "risk" refers to the chance of the cancer coming back after treatment. Using results of tumor histology tests, biology tests, and response to therapy may be able to improve treatment for children with FHWT.
Study Plan: This study plans to maintain event-free survival (EFS) for Stage I favorable histology Wilms tumor (FHWT) and to compare certain types of chemotherapy in specific stages of Wilms tumor.
STAGE I FHWT:
All patients in this study will have their kidney tumor and nearby lymph nodes removed before joining the trial. Children younger than 4 years old at diagnosis—or those of any age whose tumor has an epithelial cell type—will be closely monitored while doctors wait for tumor test results. If the tumor shows high-risk features (adverse biology), they will move to Arm I for further treatment. If the tumor has standard, low-risk features, they will stay in Arm II and continue with observation after surgery unless the cancer returns. If the disease comes back, patients with favorable tumor features will move to Arm III, while those with more aggressive or unfavorable tumors will move to Arm IV. Children who are 4 years or older at diagnosis and do not have the epithelial tumor type will be placed in Arm I, even before biology results are available.
ARM I (EE-4A): Patients receive dactinomycin and vincristine for 7 cycles of 21 days.
ARM II: Patients undergo observation without chemotherapy on study with ultrasounds and x-rays.
Arm III (DD-4A): Patients receive dactinomycin, vincristine, and doxorubicin for 9 cycles of 21 days.
Arm IV (UH-3): Patients receive dactinomycin, vincristine, cyclophosphamide, carboplatin, etoposide, and irinotecan for 14 cycles of 21 days.
STAGE II FHWT:
Patients receive one cycle of regimen EE-4A as in STAGE I FHWT Arm I. Patients with standard biology are assigned to Arm I below. Patients with adverse biology are randomized to Arm II or Arm III below.
ARM I: Patients receive cycles 2-7 of regimen EE-4A as in STAGE I FHWT Arm I.
ARM II: Patients receive cycles 2-9 of regimen VIVA: dactinomycin, vincristine, irinotecan. Treatment repeats every 21 days for 8 cycles.
ARM III: Patients receive cycles 2-9 of regimen DD-4A: dactinomycin, and doxorubicin.
STAGE III FHWT:
Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of regimen DD-4A: Dactinomycin, vincristine, doxorubicin. Patients with standard biology are assigned to Arm I below. Patients with adverse biology are assigned to Arm II below.
ARM I: Patients receive cycles 2-7 of regimen EE-4A as in STAGE I FHWT Arm I.
ARM II: Patients receive cycle 2 treatment of regimen DD-4A as in STAGE II FHWT Arm III above. They are then randomized to Arm IIA or Arm IIB below.
ARM IIA: Patients receive regimen MVI: Vincristine, dactinomycin, doxorubicin, cyclophosphamide, irinotecan, and etoposide. Treatment repeats every 21 days for 11 cycles.
ARM IIB: Patients receive regimen M: Cyclophosphamide, etoposide, vincristine, dactinomycin, and doxorubicin. Treatment repeats every 21 days for 9 cycles.
*For other arms and stages of this study, please contact the protocol coordinator below*
Eligibility Criteria
Inclusion Criteria
- All patients must be enrolled on APEC14B and consent to Part A – Eligibility Screening
- All patients must be < than 30 at the time of enrollment
- Patients with newly diagnosed Stage I-IV Favorable Histology Wilms Tumor
- Patients who have an upfront nephrectomy must have at least one lymph node sampled and confirmed as a lymph node by central pathology review to be eligible
- Adequate liver and cardiac function
Exclusion Criteria
- Patient with a diagnosis of Stage V Bilateral Wilms Tumor
- Patients who in the opinion of the investigator are not able to comply with the study procedures are not eligible
- Patients with any uncontrolled, intercurrent illness including but not limited to symptomatic congestive heart failure
- Patients with lung metastases as the only metastatic site who already had complete resection of all radiologically evident lung nodules, and have at least one nodule confirmed pathologically as tumor
- Prior therapy or concurrent therapy
- Pregnancy and breastfeeding patients are not eligible
Principal Investigator
Dr. Glenn Edwards is the section chief of Pediatric Hematology/Oncology. He's also the Children's Oncology Group's principal investigator for Carilion Clinic and has more than 30 years of clinical experience. He's board certified by the American Board of Pediatrics in Pediatrics and Pediatric Hematology/Oncology. He completed his fellowship at Walter Reed Army Medical Center and completed his internship and residency at Tripler Army Medical Center.
Contact Information
Wendy McCarty, CCRP
Clinical Research Coordinator II
Sydnee Moses, BS
Clinical Research Coordinator II
