Chemotherapy + Radiation for Kidney Cancer (Wilms' Tumor)

Not currently recruiting at 338 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Must not be taking: Aprepitant

Disqualifiers: Bilateral Wilms' tumors, Pregnancy, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining chemotherapy and radiation therapy for young patients with newly diagnosed Wilms' tumor, a type of kidney cancer. The goal is to determine if multiple chemotherapy drugs, with or without radiation, can kill more cancer cells. The trial includes various treatment plans and may involve surgery and radiation for those with specific types of tumor spread. It is designed for patients recently diagnosed with stage III or IV Wilms' tumor after surgery or biopsy. Participants must not have cancer in both kidneys or have received prior tumor treatments unless transferring from a specific previous trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take aprepitant while participating.

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

Research has shown that the drugs used in this study effectively treat various cancers, including Wilms' tumor. Here is a simplified overview of their safety records:

Cyclophosphamide, a chemotherapy drug for many cancer types, can cause side effects like infertility and birth defects but is generally safe when taken as prescribed.

Dactinomycin is used in children's cancers, including Wilms' tumor. It is very strong and handled with care, but it has proven effective for this cancer.

Doxorubicin hydrochloride can cause cancer cells to break down quickly, potentially leading to tumor lysis syndrome, a serious side effect that can be managed with medical care.

Etoposide is used for other cancers and is usually well-tolerated, though it can cause side effects such as low blood cell counts.

Liposomal vincristine sulfate, a newer version of vincristine, targets cancer cells more effectively. It allows for higher doses without increasing side effects like nerve damage, a common concern with vincristine.

Overall, these treatments have been thoroughly studied and are commonly used for Wilms' tumor. Their safety profiles are well-known, and while risks exist, they are carefully managed in a controlled clinical trial setting. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for Wilms' Tumor because it combines chemotherapy and radiation in a way that targets cancer more aggressively. Unlike the standard treatment, which often involves surgery followed by chemotherapy, this approach uses a mix of drugs like cyclophosphamide, dactinomycin, doxorubicin hydrochloride, etoposide, and liposomal vincristine sulfate. These drugs are given in different phases, with the inclusion of radiation therapy, especially for patients with metastases, aiming to improve outcomes. The potential of this regimen to shrink tumors more effectively and reduce the chance of recurrence is what makes it stand out.

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

Research shows that the drugs used in this trial hold promise for treating Wilms' tumor. In similar studies, cyclophosphamide and etoposide have helped 79% of patients avoid major health events for five years and 90% of patients survive overall. In this trial, some participants will receive a regimen including cyclophosphamide. Doxorubicin, part of the treatment regimen in this trial, improved outcomes for Stage III Wilms' tumor, with 84% of patients not experiencing a return of the tumor for eight years. Dactinomycin, also included in the trial, has been part of successful treatments for Wilms' tumor over the years. Liposomal vincristine sulfate, another drug in the trial, allows for higher doses without more side effects, potentially leading to better results. Radiation therapy, when combined with chemotherapy, has effectively improved survival rates, with over 90% of children becoming long-term survivors. ^{6 7 8 9 10}

Who Is on the Research Team?

David B Dix

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for young patients with a new diagnosis of stage III or IV Wilms' tumor. They must start treatment within two weeks after surgery or biopsy, have acceptable liver function and heart performance, and not be pregnant or breastfeeding. Those who've had prior tumor treatments (except in specific circumstances) can't join.

Inclusion Criteria

I can perform most of my daily activities without assistance.

Not pregnant or nursing

Fertile patients must use effective contraception

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Regimen DD4A (Initial)

Participants receive dactinomycin, vincristine, and doxorubicin hydrochloride. Radiotherapy is administered for patients with pulmonary and extra-pulmonary metastases.

6 weeks

Treatment - Regimen DD4A or M

Participants continue with either Regimen DD4A or switch to Regimen M based on response. Regimen DD4A includes dactinomycin, vincristine, and doxorubicin hydrochloride. Regimen M includes cyclophosphamide, etoposide, vincristine, dactinomycin, and doxorubicin hydrochloride, with whole lung radiotherapy for certain patients.

19-25 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

What Are the Treatments Tested in This Trial?

Interventions

• 3-dimensional Conformal Radiation Therapy
• Cyclophosphamide
• Dactinomycin
• Doxorubicin Hydrochloride
• Etoposide
• Liposomal Vincristine Sulfate

Trial Overview The study is examining the effectiveness of combination chemotherapy with drugs like Doxorubicin Hydrochloride and Vincristine Sulfate Liposome, either alone or combined with radiation therapy, to see if this approach better kills cancer cells in children with advanced kidney tumors.

How Is the Trial Designed?

Group I: Treatment (chemotherapy, surgery, radiotherapy) Experimental Treatment 7 Interventions

REGIMEN DD4A (weeks 1-6): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV. Patients with pulmonary and extra-pulmonary metastases at diagnosis undergo radiotherapy. Patients with initially unresectable or incompletely resected tumors are reevaluated at week 6, and if resectable, undergo surgery and then proceed to either regimen DD4A or regimen M. REGIMEN DD4A (weeks 7-25): Patients receive dactinomycin IV; vincristine IV; and doxorubicin hydrochloride IV. REGIMEN M (weeks 7-31): Patients receive cyclophosphamide IV; vincristine IV; and dactinomycin IV and doxorubicin hydrochloride IV. Patients with pulmonary metastases only who are SIR also undergo whole lung radiotherapy.

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

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 phase II study involving 12 patients with refractory renal cell cancer, pegylated-liposomal doxorubicin (Doxil) was administered with mild toxicities, primarily related to mucositis and hand-foot syndrome.

Despite the treatment being well-tolerated, no objective responses were observed in 11 evaluable patients, indicating that pegylated-liposomal doxorubicin does not demonstrate efficacy in this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of pegylated-liposomal doxorubicin (Doxil) in renal cell cancer. Skubitz, KM.[2019]

In a study of 42 adult patients with poor-risk acute leukemia, the combination of liposomal daunorubicin (DNX) and high-dose arabinosyl cytosine (HDAC) resulted in a high complete remission rate of 51% in acute non-lymphocytic leukemia (ANLL) and 91% in acute lymphocytic leukemia (ALL).

The treatment was associated with low non-hematologic toxicity, making it a safer option for elderly and heavily pretreated patients, with negligible side effects such as no intestinal toxicity and only one case of bacteremia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal daunorubicin (DaunoXome) for treatment of poor-risk acute leukemia. Russo, D., Piccaluga, PP., Michieli, M., 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT00379340

NCT00379340 | Combination Chemotherapy With or ... This phase III trial is studying how well combination chemotherapy with or without radiation therapy works in treating young patients with newly diagnosed ...

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/pbc.30627

Post‐operative flank irradiation using conformal versus ... Five-year overall survival (OS) has increased to over 90%. However, the incidence of recurrence remains around 15%. Nowadays, the treatment ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7995478/

Inter-clinician delineation variation for a new highly-conformal ... A total of 57/60 delineation sets were completed. The median DSCref/part for the CTV was 0.55 without improvement after sequential cases (case 3 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1053429697800045

Wilms' tumor: Changing role of radiation therapy Wilms' tumor is a highly curable neoplasm. Greater than 90% of all children with this disease can be expected to become long-term survivors.

5. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT00352534

UCSF Wilms Tumor Trial → Vincristine, Dactinomycin, and ... Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors.Giving these treatments ...

6. cancer.gov cancer.gov/types/kidney/hp/wilms-treatment-pdq

Wilms Tumor and Other Childhood Kidney ... The addition of cyclophosphamide at the protocol dose (10 mg/kg/d for 3 days every 6 weeks) to the combination of vincristine, dactinomycin, and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6249042/

Impact of Cyclophosphamide and Etoposide on Outcome of ... The outcome for patients with CCSK treated on NWTS-5 was similar to NWTS-4 and accomplished over a shorter treatment duration.

8. go.drugbank.com go.drugbank.com/drugs/DB00531

Cyclophosphamide: Uses, Interactions, Mechanism of Action Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Modality: Small Molecule; Groups: Approved, Investigational; Structure. 3D.

9. healio.com healio.com/clinical-guidance/drugs/cyclophosphamide

Cyclophosphamide: Uses, Side Effects & Dosage Cyclophosphamide is used to treat various types of cancer. It is a chemotherapy drug that works by slowing or stopping cell growth.

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

Wilms Tumor, Version 2.2025, NCCN Clinical Practice ... Data suggested that certain molecular markers in the tumors could be used to identify children who might be at higher risk after surgery alone; ...