Various Treatments for Wilms Tumor

Recruiting at 121 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 trial explores different treatments for children with a specific type of kidney cancer called Wilms tumor, focusing on those with favorable histology. The goal is to use tumor characteristics to tailor treatments better, aiming to lower the risk of cancer recurrence after treatment. Researchers are testing multiple treatment plans using combinations of medicines like carboplatin, dactinomycin, irinotecan, and vincristine. Children diagnosed with Stage I-IV Favorable Histology Wilms Tumor who have not undergone chemotherapy may be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatments.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that treatments like carboplatin, dactinomycin, vincristine, and irinotecan have been used in past studies with children who have Wilms tumor. These treatments are generally well-tolerated.

Vincristine and irinotecan have been safely used in young patients with a type of Wilms tumor called diffuse anaplastic Wilms tumor. In those studies, patients handled the drugs well, although some experienced common side effects like low blood counts, diarrhea, and infections.

Dactinomycin has also been tested in children with Wilms tumors. It has improved survival rates in past treatments, indicating it is effective and generally safe for children.

Carboplatin is a common chemotherapy drug often used in treatment plans for various cancers, including those in children. It can cause side effects like nausea and low blood counts, but these are usually manageable.

Since these treatments are being tested in a Phase 3 trial, they have already gone through earlier phases to check for safety. This provides a good level of confidence in their safety for use in humans, especially children with Wilms tumor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Wilms Tumor because they combine multiple chemotherapy drugs in novel regimens, potentially improving outcomes for different stages of this cancer. Unlike standard treatments like regimens using vincristine, dactinomycin, and doxorubicin in fixed doses, these investigational regimens explore various combinations and sequences, such as the use of irinotecan and carboplatin, which might enhance effectiveness. Additionally, some arms of the trial involve a more intense treatment schedule or different drug sequences, which could lead to better management of the tumor by adapting to patient responses. This approach aims to tailor therapy more precisely to the tumor's characteristics and the patient's needs, potentially offering better survival rates and fewer side effects.

What evidence suggests that this trial's treatments could be effective for Wilms Tumor?

Studies have shown that certain treatments can effectively address Wilms tumor, a type of kidney cancer in children. This trial assigns participants to different treatment arms to evaluate the effectiveness of various drugs, including carboplatin, dactinomycin, vincristine, and irinotecan. Research indicates that carboplatin achieves overall survival rates of 90% at both two and four years. Vincristine and irinotecan have produced promising results in helping children remain cancer-free, particularly in more challenging cases of Wilms tumor. This evidence suggests these drugs can reduce the likelihood of cancer recurrence after treatment. ^{1 4 6 7 8}

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 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. 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 nephrectomy 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 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 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 nephrectomy 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 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 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 nephrectomy 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

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7213587/

Activity of Vincristine and Irinotecan in Diffuse Anaplastic ... AREN0321 evaluated the activity of vincristine and irinotecan (VI) in patients with newly diagnosed diffuse anaplastic Wilms tumor (DAWT)

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24729447/

Treatment of Wilms tumor using carboplatin compared to ... Results: Two- and four-year OS rates in the carboplatin group were 90.0% and 90.0%, compared to 100.0% and 88.0%, respectively, in the non-carboplatin group.

3. ascopubs.org ascopubs.org/doi/10.1200/jco.2014.32.15_suppl.10032

A phase 2 study of vincristine and irinotecan in metastatic ... Background: Patients with metastatic diffuse anaplastic histology Wilms tumor (DAWT) had an unacceptably low 4-year event-free survival ...

4. innovationdistrict.childrensnational.org innovationdistrict.childrensnational.org/treating-wilms-tumor-with-vincristine-and-irinotecan/

Treating Wilms Tumor with vincristine and irinotecan Moreover, the additional chemotherapy agents improved cancer-free survival rates to levels unprecedented for diffuse anaplastic Wilms tumor.

5. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35713?af=R

Treatment of focal anaplastic Wilms tumor: A report from the ... Four-year event-free survival (EFS) and overall survival (OS) for stage I FAWT were 67.5% and 88.9% and for stage IV FAWT were 61.4% and 71.6%, ...

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.19.01265

Results of the Children's Oncology Group AREN0321 Study A phase 2 study of vincristine and irinotecan in metastatic diffuse anaplastic Wilms tumor: Results from the Children's Oncology Group AREN0321 ...

7. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/658675

Role of Dactinomycin in the Improved Survival of Children ... Thirty consecutive cases of histologically proved Wilms' tumor followed for a minimum of two years have been reviewed. The overall survival rate was 70%,

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10857813/

Advances in the Clinical Management of High-Risk Wilms ... Outcomes are excellent for the majority of patients with Wilms tumors (WT). However, there remain WT subgroups for which the survival rate is approximately 50% ...