Chemotherapy for Wilms Tumor

Recruiting at 181 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

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well combination chemotherapy works in treating patients with newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT) or favorable histology Wilms tumors (FHWT) that have come back (relapsed). Drugs used in chemotherapy regimens such as UH-3 (vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan) and ICE/Cyclo/Topo (ifosfamide, carboplatin, etoposide, cyclophosphamide, and topotecan) work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help doctors find out what effects, good and/or bad, regimen UH-3 has on patients with newly diagnosed DAWT and standard risk relapsed FHWT (those treated with only 2 drugs for the initial WT) and regimen ICE/Cyclo/Topo has on patients with high and very high risk relapsed FHWT (those treated with 3 or more drugs for the initial WT).

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.

What data supports the effectiveness of the drugs used in chemotherapy for Wilms Tumor?

Research shows that the combination of etoposide and carboplatin is highly effective in treating relapsed or refractory Wilms' tumor, suggesting a potential benefit of these drugs in the treatment regimen. Additionally, vincristine and irinotecan have shown activity in treating diffuse anaplastic Wilms tumor, indicating their usefulness in certain cases. ^{1 2 3 4 5}

What safety data exists for chemotherapy drugs used in Wilms Tumor treatment?

Chemotherapy drugs like carboplatin, etoposide, and vincristine have been used in treating Wilms Tumor, and they can cause side effects such as myelosuppression (reduced bone marrow activity), mucositis (inflammation of the digestive tract lining), and renal issues (kidney problems). However, with careful dose adjustments, especially for carboplatin, permanent kidney damage can be avoided. Other side effects may include nausea, vomiting, and infections, but no toxic deaths were reported in the studies. ^{2 4 5 6 7}

What makes this drug combination unique for treating Wilms tumor?

This drug combination is unique because it includes carboplatin and etoposide, which have shown promising results in treating relapsed or resistant Wilms tumor, especially when other standard drugs like vincristine and doxorubicin are not effective. The combination has demonstrated a synergistic effect, leading to significant tumor regression in cases where other treatments have failed. ^{2 4 8 9 10}

Research Team

James I Geller

Principal Investigator

Children's Oncology Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Treatment of children with stage IV favorable histology Wilms tumor: a report from the National Wilms Tumor Study Group. [2015]

2. United States 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. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Favorable response of heavily treated Wilms' tumor to paclitaxel and carboplatin. [2015]

4. United States 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. [2017]

5. United States 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. [2017]

6. England pubmed.ncbi.nlm.nih.gov

High-dose chemotherapy with autologous stem cell rescue in children with nephroblastoma. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Platinum compounds in children with cancer: toxicity and clinical management. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Preoperative chemotherapy with doxorubicin in Wilms tumor. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

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

10. Germany 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)]. [2013]