A Study of Combination Chemotherapy for Patients With Newly Diagnosed DAWT and Relapsed FHWT
Anaplastic Kidney Wilms Tumor, Recurrent Kidney Wilms Tumor, Stage II Kidney Wilms Tumor
About this trial
This is an interventional treatment trial for Anaplastic Kidney Wilms Tumor
Eligibility Criteria
Inclusion Criteria:
- Patients with newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on AREN03B2 and have received an initial risk assignment showing DAWT (if anaplasia first identified at diagnostic, pre-treatment nephrectomy or biopsy) or a delayed nephrectomy classification showing DAWT (if anaplasia first noted at delayed nephrectomy) prior to enrollment on AREN1921. Prior enrollment on AREN03B2 is not an eligibility requirement for patients with relapsed favorable histology Wilms tumor.
- Patients must be =< 30 years old at study enrollment
Patients with the following diagnoses are eligible for this study:
- 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
Patients with newly diagnosed DAWT must have had histologic verification of the malignancy. For relapsed FHWT patients, biopsy to prove recurrence is encouraged, but not required
- Note: For relapsed FHWT patients, an institutional pathology report confirming favorable histology Wilms tumor (from relapse, if available, or from original diagnosis) must be available for upload prior to initiation of protocol therapy
- Patients with newly diagnosed Stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on AREN1921 within 2 weeks of the tumor-directed surgery or biopsy procedure that first confirms a diagnosis of DAWT, whether at initial diagnostic procedure or delayed nephrectomy (such surgery/biopsy is day 0). For patients who received prior therapy for presumed favorable histology Wilms tumor, later confirmed to have diffuse anaplastic Wilms tumor at subsequent review of the initial biopsy
- Patients with newly diagnosed DAWT who undergo upfront nephrectomy must have at least 1 lymph node sampled prior to study enrollment
- Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
- Patients must have a life expectancy of >= 8 weeks
Diffuse Anaplastic Wilms Tumor: Patients with diffuse anaplastic histology must have had no prior systemic therapy, except in the following situations:
- Patients with diffuse anaplastic Wilms tumor who received no more than 12 weeks of pre nephrectomy chemotherapy for what was originally presumed to be favorable histology Wilms tumor, subsequently confirmed to be diffuse anaplastic Wilms tumor at delayed nephrectomy
- Patients with diffuse anaplastic Wilms tumor who received no more than 6 weeks of chemotherapy following upfront biopsy, initiated within 14 days of biopsy, for presumed favorable histology Wilms tumor based on institutional review, but subsequently corrected to diffuse anaplastic Wilms tumor based on the AREN03B2 initial risk assignment results (if available per current version of AREN03B2)
- Treatment consisting of vincristine/doxorubicin/cyclophosphamide initiated on an emergent basis and within allowed timing as described
- Note: 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 as noted. Patients who received radiation as part of standard of care for presumed newly diagnosed favorable histology Wilms tumor, along with chemotherapy as noted above, prior to identification of diffuse anaplasia, are also eligible
Relapsed Favorable Histology Wilms Tumor: Patients must not have received prior chemotherapy for their relapsed favorable histology Wilms tumor diagnosis. In addition, patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study
- Radiation therapy (RT): >= 2 weeks (wks) must have elapsed for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 wks must have elapsed if other substantial bone marrow (BM) radiation. Patients with relapsed favorable histology Wilms tumor who received emergency radiation to preserve organ function are eligible and do not need to washout with the above criteria
- Patients may not be receiving any other investigational agents (within 4 weeks prior to study enrollment)
- Peripheral absolute neutrophil count (ANC) >= 750/uL (performed within 7 days prior to enrollment)
- Platelet count >= 75,000/uL (transfusion independent) (performed within 7 days prior to enrollment)
- Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (performed within 7 days prior to enrollment)
Patients with high-risk or very high-risk relapsed FHWT who will be treated with regimen ICE/Cyclo/Topo, must have renal function assessed by creatinine clearance or radioisotope glomerular filtration rate (GFR) and meet the following requirement:
- Creatinine clearance or radioisotope GFR >= 60 mL/min/1.73 m^2 (performed within 7 days prior to enrollment)
Patients diagnosed with stage 2-4 DAWT or standard risk relapsed FHWT, who will be treated with regimen UH 3, may either obtain a creatinine clearance, radioisotope GFR (meeting the above criteria of GFR >= 60 mL/min/1.73 m^2), or an adequate serum creatinine as per the following table:
- Age: Maximum Serum Creatinine (mg/dL)
- 1 month to < 6 months: 0.4 (male and female)
- 6 months to < 1 year: 0.5 (male and female)
- 1 to < 2 years: 0.6 (male and female)
- 2 to < 6 years: 0.8 (male and female)
- 6 to < 10 years: 1 (male and female)
- 10 to < 13 years: 1.2 (male and female)
- 13 to < 16 years: 1.5 (male), 1.4 (female)
- >= 16 years: 1.7 (male), 1.4 (female)
- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age or direct bilirubin =< ULN for patients whose total bilirubin > 1.5 x ULN (performed within 7 days prior to enrollment)
- Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age or =< 5 x ULN for patients with liver metastases (performed within 7 days prior to enrollment)
- Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by radionuclide angiogram (obtained within 21 days prior to enrollment and start of protocol therapy)
Exclusion Criteria:
- 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
For patients with high-risk or very high-risk relapsed FHWT:
- 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
For 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
- Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
- Lactating females who plan to breastfeed their infants
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
Sites / Locations
- Children's Hospital of AlabamaRecruiting
- USA Health Strada Patient Care CenterRecruiting
- Providence Alaska Medical CenterRecruiting
- Banner Children's at DesertRecruiting
- Banner University Medical Center - TucsonRecruiting
- Arkansas Children's HospitalRecruiting
- Kaiser Permanente Downey Medical CenterRecruiting
- Loma Linda University Medical CenterRecruiting
- Miller Children's and Women's Hospital Long BeachRecruiting
- Children's Hospital Los AngelesRecruiting
- Mattel Children's Hospital UCLARecruiting
- Valley Children's HospitalRecruiting
- UCSF Benioff Children's Hospital OaklandRecruiting
- Kaiser Permanente-OaklandRecruiting
- Children's Hospital of Orange CountyRecruiting
- Lucile Packard Children's Hospital Stanford UniversityRecruiting
- University of California Davis Comprehensive Cancer CenterRecruiting
- Rady Children's Hospital - San DiegoRecruiting
- UCSF Medical Center-Mission BayRecruiting
- Children's Hospital ColoradoRecruiting
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical CenterRecruiting
- Connecticut Children's Medical CenterRecruiting
- Yale UniversityRecruiting
- Alfred I duPont Hospital for ChildrenRecruiting
- MedStar Georgetown University HospitalRecruiting
- Children's National Medical CenterRecruiting
- Golisano Children's Hospital of Southwest FloridaRecruiting
- University of Florida Health Science Center - GainesvilleRecruiting
- Memorial Regional Hospital/Joe DiMaggio Children's HospitalRecruiting
- Nemours Children's Clinic-JacksonvilleRecruiting
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- Nicklaus Children's HospitalRecruiting
- Arnold Palmer Hospital for ChildrenRecruiting
- Nemours Children's HospitalRecruiting
- Sacred Heart HospitalRecruiting
- Johns Hopkins All Children's HospitalRecruiting
- Tampa General HospitalRecruiting
- Saint Joseph's Hospital/Children's Hospital-TampaRecruiting
- Saint Mary's HospitalRecruiting
- Children's Healthcare of Atlanta - EglestonRecruiting
- Medical Center of Central GeorgiaRecruiting
- Memorial Health University Medical CenterRecruiting
- Kapiolani Medical Center for Women and ChildrenRecruiting
- Saint Luke's Cancer Institute - BoiseRecruiting
- Lurie Children's Hospital-ChicagoRecruiting
- University of IllinoisRecruiting
- University of Chicago Comprehensive Cancer CenterRecruiting
- Loyola University Medical CenterRecruiting
- Advocate Children's Hospital-Oak LawnRecruiting
- Advocate Children's Hospital-Park RidgeRecruiting
- Saint Jude Midwest AffiliateRecruiting
- Southern Illinois University School of MedicineRecruiting
- Riley Hospital for ChildrenRecruiting
- Blank Children's HospitalRecruiting
- University of Iowa/Holden Comprehensive Cancer CenterRecruiting
- University of Kentucky/Markey Cancer CenterRecruiting
- Norton Children's HospitalRecruiting
- Children's Hospital New OrleansRecruiting
- Ochsner Medical Center JeffersonRecruiting
- Eastern Maine Medical Center
- Maine Children's Cancer ProgramRecruiting
- Sinai Hospital of BaltimoreRecruiting
- Johns Hopkins University/Sidney Kimmel Cancer CenterRecruiting
- Tufts Children's Hospital
- Dana-Farber Cancer InstituteRecruiting
- UMass Memorial Medical Center - University CampusRecruiting
- C S Mott Children's HospitalRecruiting
- Children's Hospital of MichiganRecruiting
- Michigan State University Clinical CenterRecruiting
- Helen DeVos Children's Hospital at Spectrum HealthRecruiting
- Bronson Methodist HospitalRecruiting
- Beaumont Children's Hospital-Royal OakRecruiting
- Children's Hospitals and Clinics of Minnesota - MinneapolisRecruiting
- University of Minnesota/Masonic Cancer CenterRecruiting
- Mayo Clinic in RochesterRecruiting
- University of Mississippi Medical CenterRecruiting
- Columbia RegionalRecruiting
- Children's Mercy Hospitals and ClinicsRecruiting
- Cardinal Glennon Children's Medical CenterRecruiting
- Washington University School of MedicineRecruiting
- Mercy Hospital Saint LouisRecruiting
- Children's Hospital and Medical Center of OmahaRecruiting
- University of Nebraska Medical CenterRecruiting
- University Medical Center of Southern NevadaRecruiting
- Sunrise Hospital and Medical CenterRecruiting
- Alliance for Childhood Diseases/Cure 4 the Kids FoundationRecruiting
- Summerlin Hospital Medical CenterRecruiting
- Renown Regional Medical CenterRecruiting
- Hackensack University Medical CenterRecruiting
- Morristown Medical CenterRecruiting
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University HospitalRecruiting
- Saint Joseph's Regional Medical CenterRecruiting
- Albany Medical CenterRecruiting
- Montefiore Medical Center - Moses CampusRecruiting
- Roswell Park Cancer InstituteRecruiting
- The Steven and Alexandra Cohen Children's Medical Center of New YorkRecruiting
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer CenterRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- NYP/Weill Cornell Medical CenterRecruiting
- Stony Brook University Medical CenterRecruiting
- State University of New York Upstate Medical UniversityRecruiting
- New York Medical CollegeRecruiting
- Mission HospitalRecruiting
- Carolinas Medical Center/Levine Cancer InstituteRecruiting
- Novant Health Presbyterian Medical CenterRecruiting
- Duke University Medical CenterRecruiting
- East Carolina UniversityRecruiting
- Wake Forest University Health SciencesRecruiting
- Sanford Broadway Medical CenterRecruiting
- Children's Hospital Medical Center of AkronRecruiting
- Cincinnati Children's Hospital Medical CenterRecruiting
- Rainbow Babies and Childrens HospitalRecruiting
- Cleveland Clinic FoundationRecruiting
- Nationwide Children's HospitalRecruiting
- Dayton Children's HospitalRecruiting
- ProMedica Toledo Hospital/Russell J Ebeid Children's HospitalRecruiting
- University of Oklahoma Health Sciences CenterRecruiting
- Legacy Emanuel Children's HospitalRecruiting
- Oregon Health and Science UniversityRecruiting
- Lehigh Valley Hospital-Cedar CrestRecruiting
- Geisinger Medical CenterRecruiting
- Penn State Children's HospitalRecruiting
- Children's Hospital of PhiladelphiaRecruiting
- Saint Christopher's Hospital for ChildrenRecruiting
- Children's Hospital of Pittsburgh of UPMCRecruiting
- Rhode Island HospitalRecruiting
- Medical University of South CarolinaRecruiting
- Prisma Health Richland HospitalRecruiting
- BI-LO Charities Children's Cancer CenterRecruiting
- Sanford USD Medical Center - Sioux FallsRecruiting
- T C Thompson Children's HospitalRecruiting
- East Tennessee Childrens HospitalRecruiting
- Saint Jude Children's Research HospitalRecruiting
- The Children's Hospital at TriStar CentennialRecruiting
- Vanderbilt University/Ingram Cancer CenterRecruiting
- Texas Tech University Health Sciences Center-AmarilloRecruiting
- Dell Children's Medical Center of Central TexasRecruiting
- Driscoll Children's HospitalRecruiting
- Medical City Dallas HospitalRecruiting
- UT Southwestern/Simmons Cancer Center-DallasRecruiting
- El Paso Children's HospitalRecruiting
- Cook Children's Medical CenterRecruiting
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer CenterRecruiting
- M D Anderson Cancer CenterRecruiting
- Covenant Children's HospitalRecruiting
- UMC Cancer Center / UMC Health SystemRecruiting
- Children's Hospital of San AntonioRecruiting
- Methodist Children's Hospital of South TexasRecruiting
- University of Texas Health Science Center at San AntonioRecruiting
- Primary Children's HospitalRecruiting
- University of Virginia Cancer CenterRecruiting
- Inova Fairfax HospitalRecruiting
- Children's Hospital of The King's DaughtersRecruiting
- Virginia Commonwealth University/Massey Cancer CenterRecruiting
- Carilion Children'sRecruiting
- Seattle Children's HospitalRecruiting
- Providence Sacred Heart Medical Center and Children's HospitalRecruiting
- Mary Bridge Children's Hospital and Health CenterRecruiting
- Madigan Army Medical CenterRecruiting
- West Virginia University Charleston DivisionRecruiting
- Edwards Comprehensive Cancer CenterRecruiting
- University of Wisconsin Carbone Cancer CenterRecruiting
- Marshfield Medical Center-MarshfieldRecruiting
- Children's Hospital of WisconsinRecruiting
- John Hunter Children's HospitalRecruiting
- Sydney Children's HospitalRecruiting
- The Children's Hospital at WestmeadRecruiting
- Queensland Children's HospitalRecruiting
- Women's and Children's Hospital-AdelaideRecruiting
- Monash Medical Center-Clayton Campus
- Royal Children's HospitalRecruiting
- Perth Children's HospitalRecruiting
- Alberta Children's HospitalRecruiting
- University of Alberta HospitalRecruiting
- British Columbia Children's HospitalRecruiting
- CancerCare ManitobaRecruiting
- Janeway Child Health CentreRecruiting
- IWK Health CentreRecruiting
- McMaster Children's Hospital at Hamilton Health SciencesRecruiting
- Children's HospitalRecruiting
- Children's Hospital of Eastern OntarioRecruiting
- Hospital for Sick ChildrenRecruiting
- The Montreal Children's Hospital of the MUHCRecruiting
- Centre Hospitalier Universitaire Sainte-JustineRecruiting
- Centre Hospitalier Universitaire de Sherbrooke-FleurimontRecruiting
- Centre Hospitalier Universitaire de QuebecRecruiting
- Starship Children's HospitalRecruiting
- Christchurch HospitalRecruiting
- HIMA San Pablo Oncologic HospitalRecruiting
- University Pediatric HospitalRecruiting
- King Faisal Specialist Hospital and Research CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm I (Regimen UH-3)
Arm II (Regimen ICE/Cyclo/Topo)
See outline in detailed description section.
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.