Various Treatments for Wilms Tumor

Recruiting at 68 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Must not be taking: Concurrent chemotherapy

Disqualifiers: Stage V Wilms, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 14 cycles, each cycle lasting 3 weeks

1656 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss your current medications with the trial team to get specific guidance.

What safety data exists for treatments like Carboplatin, Dactinomycin, Irinotecan, Vincristine, and Patient Observation in Wilms Tumor?

Vincristine and irinotecan have been used in Wilms tumor treatments with main side effects being blood-related issues and diarrhea, but without excessive toxicity. Carboplatin, when used in high doses, can cause blood-related side effects and affect kidney function, but no permanent kidney damage was observed with dose adjustments. In single doses, carboplatin showed acceptable toxicity with no kidney or liver damage. ^{1 2 3 4 5}

How does the drug combination of Carboplatin, Dactinomycin, Irinotecan, and Vincristine differ from other treatments for Wilms Tumor?

This drug combination is unique because it includes carboplatin, which has been used as an alternative when actinomycin-D was unavailable, and combines it with vincristine and irinotecan, which have shown activity in treating diffuse anaplastic Wilms tumor. This regimen aims to improve outcomes by using a mix of drugs that have been effective in different settings of Wilms tumor treatment. ^{1 2 6 7 8}

What data supports the effectiveness of the drug carboplatin in treating Wilms tumor?

Research shows that carboplatin, when used as a single-dose treatment in children with untreated stage IV Wilms' tumor, resulted in a 78% partial response rate and a 62% median tumor volume reduction, indicating its effectiveness in this setting. ^{1 2 4 5 7}

Who Is on the Research Team?

Elizabeth A Mullen

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for children under 30 years old with a specific kidney cancer called Favorable Histology Wilms Tumor (FHWT). They must be newly diagnosed, have not started treatment, and their tumor must be reviewed centrally. A lymph node sample is required at surgery. Patients need to enroll in another study first (APEC14B1) and meet certain molecular test requirements.

Inclusion Criteria

I am enrolled in APEC14B1 and agreed to the initial screening.

I am under 30 years old.

My Wilms tumor is newly diagnosed, stage I-IV, and has a favorable outlook.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various chemotherapy regimens based on risk stratification and tumor biology, including EE-4A, DD-4A, VIVA, MVI, and UH-3 regimens.

Up to 14 cycles, each cycle lasting 3 weeks

Multiple visits for chemotherapy administration and imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with regular imaging and clinical assessments.

10 years

Regular follow-up visits with imaging

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Dactinomycin
• Irinotecan
• Patient Observation
• Vincristine

Trial Overview The trial tests how risk factors like tumor histology, biology tests, and therapy response can guide treatment for FHWT in children. It includes drugs like Vincristine and Doxorubicin, imaging tests such as CT scans and MRIs, surgery (nephrectomy), and patient observation to see if these tailored treatments can prevent cancer relapse.

How Is the Trial Designed?

Group I: Stage IV Lung Metastases Arm III (DD-4A, MVI) Experimental Treatment 11 Interventions

Patients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group II: Stage IV Lung Metastases Arm II (DD-4A, MVI) Experimental Treatment 10 Interventions

Patients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group III: Stage IV Lung Metastases Arm I (DD-4A) Experimental Treatment 7 Interventions

Patients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive cycles 3-9 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) Arms V and VA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group IV: Stage IV Extrapulmonary Arm X (M) Experimental Treatment 10 Interventions

Patients in Stage IV Extrapulmonary Arm X receive cycles 5-11 (or 4-11 if nephrecromy occurred after cycle 3) of regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.

Group V: Stage IV Extrapulmonary Arm VIII (UH-3) Experimental Treatment 12 Interventions

Patients in Stage IV Extrapulmonary Arm VIII receive regimen UH-3 as in STAGE I FHWT Arm IV above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.

Group VI: Stage IV Extrapulmonary Arm VII (DD-4A, M) Experimental Treatment 11 Interventions

Patients in Stage IV Extrapulmonary Arm VII receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive cycles 3-4 of regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.

Group VII: Stage IV Extrapulmonary Arm VI (DD-4A, MVI) Experimental Treatment 12 Interventions

Patients in Stage IV Extrapulmonary Arm VI receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive cycles 3-4 of regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.

Group VIII: Stage IV Extrapulmonary Arm V (DD-4A, UH-3) Experimental Treatment 13 Interventions

Patients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen UH-3 as in STAGE I FHWT Arm IV above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.

Group IX: Stage IV Extrapulmonary Arm IX (MVI) Experimental Treatment 11 Interventions

Patients in Stage IV Extrapulmonary Arm IX receive cycles 5-13 (or 4-13 if nephrecromy occurred after cycle 3) of regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.

Group X: Stage IV Extrapulmonary Arm IV (DD-4A, M) Experimental Treatment 11 Interventions

Patients in Stage IV Extrapulmonary Arm IV receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.

Group XI: Stage IV Extrapulmonary Arm III (DD-4A, MVI) Experimental Treatment 11 Interventions

Patients in Stage IV Extrapulmonary Arm III receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.

Group XII: Stage IV Extrapulmonary Arm II (DD-4A, M) Experimental Treatment 11 Interventions

Patients in Stage IV Extrapulmonary Arm II receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.

Group XIII: Stage IV Extrapulmonary Arm I (DD-4A, MVI) Experimental Treatment 12 Interventions

Patients in Stage IV Extrapulmonary Arm I receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial. Patients with metastatic sites outside the chest/abdomen/pelvis documented during therapy may undergo bone scan and/or PET.

Group XIV: Stage IV Arm X-Upfront-Delayed (M) Experimental Treatment 11 Interventions

Patients receive cycles 5-11 (or 4-11 if nephrecromy occurred after cycle 3) of regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XV: Stage IV Arm VIII-Upfront-Delayed (UH-3) Experimental Treatment 12 Interventions

Patients in Stage IV Arm VIII Upfront-Delayed receive regimen UH-3 as in STAGE I FHWT Arm IV above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XVI: Stage IV Arm VII-Upfront-Delayed (DD-4A, M) Experimental Treatment 11 Interventions

Patients in Stage IV Arm VII Upfront-Delayed receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive cycles 3-4 of regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XVII: Stage IV Arm VI-Upfront-Delayed (DD-4A, MVI) Experimental Treatment 12 Interventions

Patients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive cycles 3-4 of regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XVIII: Stage IV Arm VB-Upfront-Delayed (M) Experimental Treatment 11 Interventions

Patients receive regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XIX: Stage IV Arm VA-Upfront-Delayed (DD-4A) Experimental Treatment 7 Interventions

Patients receive cycles 5-9 (or 4-9 if nephrectomy occurred after cycle 3) of regimen DD-4A as in STAGE II FHWT Arm II above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XX: Stage IV Arm V-Upfront-Delayed (DD-4A) Experimental Treatment 8 Interventions

Patients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive cycles 3-4 of regimen DD-4A as in STAGE II FHWT Arm II above. They then undergo delayed nephrectomy after cycle 3 or 4. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXI: Stage IV Arm IX-Upfront-Delayed (MVI) Experimental Treatment 12 Interventions

Patients in Stage IV Arm IX Upfront-Delayed receive cycles 5-13 (or 4-13 if nephrecromy occurred after cycle 3) of regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXII: Stage IV Arm IV-Upfront-Delayed (DD-4A, M) Experimental Treatment 11 Interventions

Patients in Stage IV Arm IV Upfront-Delayed receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXIII: Stage IV Arm III-Upfront-Delayed (DD-4A, MVI) Experimental Treatment 12 Interventions

Patients in Stage IV Arm III Upfront-Delayed receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXIV: Stage IV Arm II-Upfront-Delayed (DD-4A, UH-3) Experimental Treatment 13 Interventions

Patients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive regimen UH-3 as in STAGE I FHWT Arm IV above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXV: Stage IV Arm I-Upfront-Delayed (DD-4A, EE-4A) Experimental Treatment 7 Interventions

Patients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive cycles 3-7 of regimen EE-4A as in STAGE I FHWT Arm I above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXVI: Stage III, Arm X-Upfront/Delayed (M) Experimental Treatment 11 Interventions

Patients receive cycles 5-11 (or 4-11 if nephrecromy occurred after cycle 3) of regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXVII: Stage III, Arm VIII-Upfront/Delayed (UH-3) Experimental Treatment 12 Interventions

Patients receive regimen UH-3 as in STAGE I FHWT Arm IV above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXVIII: Stage III, Arm VII-Upfront/Delayed (DD-4A, M) Experimental Treatment 11 Interventions

Patients receive cycles 1-2 of regimen DD-4A as in STAGE III FHWT (UPFRONT BIOPSY/DELAYED NEPHRECTOMY) above. Patients receive cycles 3-4 of regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXIX: Stage III, Arm VI-Upfront/Delayed (DD-4A, MVI) Experimental Treatment 12 Interventions

Patients receive cycles 1-2 of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycle 1, vincristine IV on days 1, 8, and 15 of cycles 1-2, and doxorubicin IV over 3-15 minutes on day 1 of cycle 2. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients receive cycles 3-4 of regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXX: Stage III, Arm VB-Upfront/Delayed (M) Experimental Treatment 9 Interventions

Patients receive cycles 5-9 (or 4-9 if nephrectomy occurred after cycle 3) of regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXXI: Stage III, Arm VA-Upfront/Delayed (DD-4A) Experimental Treatment 7 Interventions

Patients receive cycles 5-9 (or 4-9 if nephrectomy occurred after cycle 3) of regimen DD-4A as in STAGE II FHWT Arm III above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXXII: Stage III, Arm V-Upfront/Delayed (DD-4A) Experimental Treatment 8 Interventions

Patients receive cycles 1-2 of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycle 1, vincristine IV on days 1, 8, and 15 of cycles 1-2, and doxorubicin IV over 3-15 minutes on day 1 of cycle 2. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients receive cycles 3-4 of regimen DD-4A as in STAGE II FHWT Arm III above. They then undergo delayed nephrectomy after cycle 3 or 4. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXXIII: Stage III, Arm IX-Upfront/Delayed (MVI) Experimental Treatment 12 Interventions

Patients receive cycles 5-13 (or 4-13 if nephrecromy occurred after cycle 3) of regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXXIV: Stage III, Arm IV-Upfront/Delayed (DD-4A, M) Experimental Treatment 11 Interventions

Patients receive cycles 1-2 of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycle 1, vincristine IV on days 1, 8, and 15 of cycles 1-2, and doxorubicin IV over 3-15 minutes on day 1 of cycle 2. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients receive regimen M as in STAGE III FHWT Arm IIB above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXXV: Stage III, Arm III-Upfront/Delayed (DD-4A, MVI) Experimental Treatment 12 Interventions

Patients receive cycles 1-2 of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycle 1, vincristine IV on days 1, 8, and 15 of cycles 1-2, and doxorubicin IV over 3-15 minutes on day 1 of cycle 2. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients receive regimen MVI as in STAGE III FHWT Arm IIA above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXXVI: Stage III, Arm IIB (M) Experimental Treatment 11 Interventions

Patients receive regimen M: Cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, etoposide IV over 60-120 minutes daily on days 1-5 of cycles 3, 4, 7, \& 9, vincristine IV on days 8 \& 15 of cycles 3 \& 4 and day 1 of cycles 5, 6, 8, 10, \& 11, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 5, 6, 8, 10, \& 11, and doxorubicin IV over 3-15 minutes of cycles 5, 6, 8, 10, \& 11. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity.

Group XXXVII: Stage III, Arm IIA (MVI) Experimental Treatment 12 Interventions

Patients receive regimen MVI: Vincristine IV on days 1, 8, \& 15 of cycle 3, days 8 \& 15 of cycle 4, and day 1 of cycles 5 \& 7-13, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, doxorubicin IV over 3-15 minutes on day 1 of cycles 3, 7, 9, 11, \& 13, cyclophosphamide IV over 15-30 minutes daily on days 1-5 of cycles 4 and 6, irinotecan IV over 90 minutes daily on days 1-5 of cycles 5, 8, 10 \& 12, and etoposide IV over 60-120 minutes daily on days 1-5 of cycles 4 and 6. Treatment repeats every 21 days for 11 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXXVIII: Stage III, Arm II-Upfront/Delayed (DD-4A, UH-3) Experimental Treatment 11 Interventions

Patients receive cycles 1-2 of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycle 1, vincristine IV on days 1, 8, and 15 of cycles 1-2, and doxorubicin IV over 3-15 minutes on day 1 of cycle 2. Patients receive regimen UH-3 as in STAGE I FHWT Arm IV above: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XXXIX: Stage III, Arm II (DD-4A) Experimental Treatment 7 Interventions

Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 1, 3, 5, 7, \& 9, vincristine IV on days 1, 8, \& 15 of cycles 1-3 and day 1 of cycles 4-9, doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Patients with adverse biology receive cycle 2 treatment of regimen DD-4A as in STAGE II FHWT Arm III above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XL: Stage III, Arm I-Upfront/Delayed (DD-4A, EE-4A) Experimental Treatment 7 Interventions

Patients receive cycles 1-2 of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycle 1, vincristine IV on days 1, 8, and 15 of cycles 1-2, and doxorubicin IV over 3-15 minutes on day 1 of cycle 2. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients receive cycles 3-7 of regimen EE-4A as in STAGE I FHWT Arm I above. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XLI: Stage III, Arm I (DD-4A, EE-4A) Experimental Treatment 7 Interventions

Patients able to undergo an upfront nephrectomy receive cycle 1 treatment of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 1, 3, 5, 7, \& 9, vincristine IV on days 1, 8, \& 15 of cycles 1-3 and day 1 of cycles 4-9, doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Patients with standard biology receive cycles 2-7 of regimen EE-4A as in STAGE I FHWT Arm I. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XLII: Stage II, Arm III (EE-4A, DD-4A) Experimental Treatment 7 Interventions

Patients receive one cycle of regimen EE-4A as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, and 9, vincristine IV on days 1, 8, and 15 of cycles 2-3 and day 1 of cycles 4-9, and doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XLIII: Stage II, Arm II (EE-4A, VIVA) Experimental Treatment 7 Interventions

Patients receive one cycle of regimen EE-4A as in STAGE I FHWT Arm I. Patients receive cycles 2-9 of regimen VIVA: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 3, 5, 7, \& 9, vincristine IV on days 1, 8, \& 15 of cycles 2-3 and day 1 of cycles 4-9, irinotecan IV over 90 minutes daily on days 1-5 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XLIV: Stage II, Arm I (EE-4A) Experimental Treatment 6 Interventions

Patients receive one cycle of regimen EE-4A as in STAGE I FHWT Arm I. Patients receive cycles 2-7 of regimen EE-4A as in STAGE I FHWT Arm I. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XLV: Stage I, Arm IV (UH-3) Experimental Treatment 10 Interventions

Patients receive regimen UH-3: Vincristine IV on days 1, 8, \& 15 of cycles 1, 5, 7, 10, \& 13, and days 1 \& 8 of cycles 3, 4, 8, \& 11, doxorubicin IV 3-15 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 5, 7, 10, \& 13, and days 1-4 of cycles 2, 6, 9, 12, \& 14, carboplatin IV over 15-60 minutes on day 1 of cycles 2, 6, 9, 12, and 14, etoposide IV over 60-120 minutes on days 1-4 of cycles 2, 6, 9, 12, \& 14, and irinotecan IV over 90 minutes on days 1-5 of cycles 3, 4, 8, \& 11. Treatment repeats every 21 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XLVI: Stage I, Arm III (DD-4A) Experimental Treatment 7 Interventions

Patients receive regimen DD-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 1, 3, 5, 7, \& 9, vincristine IV on days 1, 8, \& 15 of cycles 1-3 and day 1 of cycles 4-9, doxorubicin IV over 3-15 minutes on day 1 of cycles 2, 4, 6, \& 8. Treatment repeats every 21 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Group XLVII: Stage I, Arm II (observation) Experimental Treatment 3 Interventions

Patients undergo observation without chemotherapy on study with ultrasounds and x-rays.

Group XLVIII: Stage I, Arm I (EE-4A) Experimental Treatment 7 Interventions

Patients receive regimen EE-4A: Dactinomycin IV over 1-5 or 10-15 minutes on day 1 of cycles 1-7 and vincristine IV on days 1, 8, \& 15 of cycles 1-3 and day 1 of cycles 4-7. Treatment repeats every 21 days for 7 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, CT or MRI, ultrasound, and X-ray imaging throughout the trial.

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

Published Research Related to This Trial

A 17-year-old patient with heavily treated Wilms' tumor and multiple metastases showed a partial response to a combination of carboplatin and paclitaxel after experiencing multiple relapses and extensive prior treatments.

The treatment resulted in mild toxicity and a time to progression of 200 days, indicating that this chemotherapy combination can be effective in managing refractory cases of Wilms' tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Favorable response of heavily treated Wilms' tumor to paclitaxel and carboplatin. Ozaki, S., Takigawa, N., Ichihara, E., et al.[2015]

In a phase II study involving 26 patients with relapsed or refractory Wilms' tumor, the combination of etoposide and carboplatin showed a high overall response rate of 73%, with 8 patients achieving complete response and 11 achieving partial remission.

While the treatment demonstrated impressive efficacy, it also resulted in significant hematologic toxicity, particularly severe thrombocytopenia, highlighting the need for careful monitoring and management of side effects in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide and carboplatin: a highly effective combination in relapsed or refractory Wilms' tumor--a phase II study by the French Society of Pediatric Oncology. Pein, F., Tournade, MF., Zucker, JM., et al.[2017]

In the AREN0321 study, vincristine and irinotecan (VI) showed a high response rate in patients with newly diagnosed stage IV diffuse anaplastic Wilms tumor, with 79% of patients achieving a complete or partial response after two cycles.

The study indicated improved four-year survival rates for patients treated with regimen UH1 compared to historical controls from the National Wilms Tumor Study 5, although this came with increased toxicity, highlighting the need for further modifications to reduce adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of Vincristine and Irinotecan in Diffuse Anaplastic Wilms Tumor and Therapy Outcomes of Stage II to IV Disease: Results of the Children's Oncology Group AREN0321 Study. Daw, NC., Chi, YY., Kalapurakal, JA., et al.[2021]

High-dose chemotherapy (HDC) combined with autologous stem cell rescue improved survival rates in children with Wilms tumor who had a high risk of relapse, with a 60.9% estimated survival rate and 48.2% event-free survival after a median follow-up of 41 months.

While HDC was effective, it was associated with significant toxicities, including hematologic issues, mucositis, and renal dysfunction; however, careful dose adjustments based on kidney function prevented permanent renal failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose chemotherapy with autologous stem cell rescue in children with nephroblastoma. Kremens, B., Gruhn, B., Klingebiel, T., et al.[2013]

Chemotherapy, particularly with actinomycin-D and vincristine, has significantly improved survival rates for localized Wilms' tumor to over 80% and about 50% for metastatic cases, indicating its efficacy when combined with surgery and radiotherapy.

Initial studies suggest that combining actinomycin-D and vincristine may be more effective than using either drug alone, while the role of postoperative radiotherapy in fully resected tumors is still being evaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the treatment of Wilms' tumor. Wolff, JA.[2019]

Citations

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