Chemotherapy for Wilms Tumor

Recruiting at 212 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Oncology Group

Must not be taking: St. John's wort

Disqualifiers: Bilateral Wilms tumor, Active infection, others

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

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

Compensation: Varies

Number of Visits: 21

Duration: 42 weeks

256 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of specific chemotherapy combinations for treating different types of Wilms tumors, a form of kidney cancer. It examines two treatment plans: one for patients with newly diagnosed diffuse anaplastic Wilms tumors and another for those whose favorable histology Wilms tumors have relapsed. The goal is to determine how well these drug combinations stop tumor growth. Suitable participants include those newly diagnosed with stages 2-4 diffuse anaplastic Wilms tumor or those who have experienced a relapse of favorable histology Wilms tumor. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use St. John's wort during the trial, and you must not be on any other investigational drugs within 4 weeks before joining the study.

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

Research has shown that the UH-3 and ICE/Cyclo/Topo chemotherapy treatments are under study for their safety and effectiveness in treating Wilms tumors. These treatments involve drugs such as vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, irinotecan, ifosfamide, and topotecan.

Patients in past studies have tolerated these drugs well, though side effects may occur. Common side effects of chemotherapy include nausea, hair loss, and fatigue. More serious side effects can occur, depending on the specific drugs and doses used.

As this trial is in an early stage, detailed safety information specific to the UH-3 and ICE/Cyclo/Topo treatments may not yet be fully available. However, these drugs have been used in other treatments, providing some reassurance about their safety in humans.

The medical team closely monitors participants in these trials, managing and reporting any side effects. Potential participants should discuss possible risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatment regimens for Wilms Tumor because they introduce a novel combination of drugs and treatment cycles that differ from standard care. The ICE/Cyclo/Topo regimen uniquely combines carboplatin, etoposide, and ifosfamide with cyclophosphamide and topotecan in alternating cycles, potentially offering a tailored approach to targeting tumor cells. Moreover, the UH-3 regimen, although not detailed, suggests another innovative approach under investigation. These treatments are also integrated with surgery and imaging techniques, providing a comprehensive attack on the cancer, which could lead to improved outcomes compared to traditional chemotherapy regimens.

What evidence suggests that this trial's chemotherapy regimens could be effective for Wilms tumor?

Research has shown that the combination of chemotherapy treatments in this trial may effectively treat Wilms tumors. Participants will be assigned to one of two treatment arms. The ICE/Cyclo/Topo regimen, one of the study arms, uses a mix of drugs to attack cancer cells in various ways, potentially preventing the cancer from spreading. For patients with diffuse anaplastic Wilms tumors, early results suggest these treatments might outperform previous ones. The UH-3 regimen, another treatment arm, also combines several chemotherapy drugs and aims to improve survival rates for those with high-risk or recurrent Wilms tumors. While each patient is unique, these treatments aggressively target the tumors, offering hope for better outcomes in challenging cases. ^{1 2 6 7 8}

Who Is on the Research Team?

James I Geller

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for individuals up to 30 years old with newly diagnosed stage II-IV diffuse anaplastic Wilms tumors or those whose favorable histology Wilms tumor has relapsed. They must have a certain level of physical ability, life expectancy over 8 weeks, and meet specific health criteria including heart, blood count, kidney and liver function. Pregnant women, patients with bilateral tumors or uncontrolled illnesses are excluded.

Inclusion Criteria

I am 30 years old or younger.

I meet the requirements for chemotherapy, radiation, and trial treatments.

My diagnosis is stage 2-4 diffuse anaplastic Wilms tumor or it's a first relapse of favorable histology Wilms tumor.

Exclusion Criteria

I have chronic bowel issues or blockage and my cancer is in stages 2-4 or has come back.

I am currently using St. John's wort.

My FHWT has returned and I've had limited or no initial chemotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination chemotherapy with regimens UH-3 or ICE/Cyclo/Topo, including cycles of vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, irinotecan, ifosfamide, and topotecan, with surgery and/or radiation therapy as clinically indicated.

42 weeks

Multiple visits for chemotherapy cycles every 21 days

Radiation

Participants undergo radiation therapy at week 7 of cycle 3 as clinically indicated.

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits every 3 months for years 1-2, every 6 months for years 3-4, and once at year 5.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cyclophosphamide
• Doxorubicin
• Etoposide
• ICE/Cyclo/Topo
• Irinotecan
• UH-3
• Vincristine

Trial Overview The study tests combination chemotherapy regimens UH-3 (vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide & irinotecan) for new DAWT cases & ICE/Cyclo/Topo (ifosfamide, carboplatin etoposide cyclophosphamide & topotecan) for high-risk relapsed FHWT. It aims to see how these drugs affect tumor growth by killing cells or stopping them from dividing/spreading.

How Is the Trial Designed?

Group I: Arm II (Regimen ICE/Cyclo/Topo) Experimental Treatment 15 Interventions

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.

Group II: Arm I (Regimen UH-3) Experimental Treatment 15 Interventions

See outline in detailed description section.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a case of a 4-year-old girl with anaplastic Wilms' tumor that did not respond to standard preoperative chemotherapy, treatment with carboplatin and etoposide led to remarkable tumor regression after just one cycle.

The combination of carboplatin and etoposide proved effective for resistant Wilms' tumor, resulting in complete remission after six cycles, although it caused severe side effects like bone marrow aplasia and a temporary decrease in kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Complete remission of a highly malignant, progressive under therapy Wilm's tumor using the combination carboplatin and etoposide (VP 16)]. Walka, MM., Schröter, W., Lakomek, M.[2013]

The addition of doxorubicin to the treatment regimen of vincristine and actinomycin D did not significantly improve the four-year relapse-free survival rate for children with stage IV favorable histology Wilms tumor, with rates of 57.7% for the combination versus 53.3% without it.

Similarly, adding cyclophosphamide to the three-drug regimen did not enhance relapse-free survival, suggesting that some children with stage IV Wilms tumor may be effectively treated without anthracyclines, highlighting the need for future research to identify this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of children with stage IV favorable histology Wilms tumor: a report from the National Wilms Tumor Study Group. Green, DM., Breslow, NE., Evans, I., et al.[2015]

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]

Cisplatin, carboplatin, and oxaliplatin are effective treatments for various pediatric tumors, but they have different toxic effects: cisplatin is primarily ototoxic and nephrotoxic, carboplatin mainly causes myelosuppression, and oxaliplatin leads to peripheral sensory neurotoxicity.

Understanding the pharmacokinetics and toxic profiles of these platinum compounds can help doctors implement strategies to prevent side effects, ultimately improving the quality of life for children undergoing cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum compounds in children with cancer: toxicity and clinical management. Ruggiero, A., Trombatore, G., Triarico, S., et al.[2022]

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]

In a study of 12 patients with Wilms tumor, preoperative chemotherapy using vincristine and doxorubicin led to significant tumor shrinkage within 4 weeks, indicating its efficacy as an alternative treatment.

All patients underwent surgery without complications and remained in remission during a median follow-up of 8 months, suggesting that this chemotherapy regimen is safe and effective for preoperative management of Wilms tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative chemotherapy with doxorubicin in Wilms tumor. Küpeli, S., Bilici, S.[2015]

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]

In a study of 29 pediatric patients with high-risk recurrent Wilms' tumor, about 50% achieved continuous complete response (CR) at a median follow-up of 48.5 months after receiving a three-drug chemotherapy regimen followed by autologous stem-cell rescue.

Despite significant treatment-related toxicities, including severe hematologic and gastrointestinal side effects, the study suggests that early high-dose chemotherapy improves outcomes for these very high-risk patients, indicating a need for new treatment strategies for those who do not respond adequately.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose melphalan, etoposide, and carboplatin followed by autologous stem-cell rescue in pediatric high-risk recurrent Wilms' tumor: a French Society of Pediatric Oncology study. Pein, F., Michon, J., Valteau-Couanet, D., et al.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04322318

NCT04322318 | A Study of Combination Chemotherapy for ... This phase II trial studies how well combination chemotherapy works in treating patients with newly diagnosed stage II-IV diffuse anaplastic Wilms tumors ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCT04322318

A Study of Combination Chemotherapy for Patients with ... This phase II trial studies how well combination chemotherapy works in treating patients with newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT)

3. cincinnatichildrens.org cincinnatichildrens.org/service/c/clinical-trials/studies/AREN-1921

AREN-1921: A Study of Combination Chemotherapy for ... This phase II trial studies how well combination chemotherapy works in treating patients with newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT)

4. mskcc.org mskcc.org/cancer-care/clinical-trials/20-512

A Phase II Study of Combination Chemotherapy, Surgery, ... This study is evaluating the safety and effectiveness of combination chemotherapy, surgery, and radiation therapy in children and young adults

5. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2021-0390.html

COGAREN1921 Treatment of Newly Diagnosed Diffuse ... This phase II trial studies how well combination chemotherapy works in treating patients with newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT) ...

6. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/wilms-tumor

Wilms Tumor Clinical Trials The purpose of this study is to evaluate how well combination chemotherapy works in treating patients with newly diagnosed stage II-IV diffuse anaplastic Wilms ...

7. jnccn.org jnccn.org/view/journals/jnccn/23/8/article-p319.xml?print

Wilms Tumor, Version 2.2025, NCCN Clinical Practice ... ... are high risk through the use of the new UH-3 regimen (vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan).

8. georgiacancerinfo.org georgiacancerinfo.org/trialDetailPrint.aspx?trialID=4985

Clinical Trial Details | GCI This phase II trial studies how well combination chemotherapy works in treating patients with newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT)