Chemotherapy + Radiation for Kidney Cancer (Wilms' Tumor)

Recruiting at 329 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

395 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial is studying how well combination chemotherapy with or without radiation therapy works in treating young patients with newly diagnosed stage III or stage IV Wilms' tumor. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving more than one drug (combination chemotherapy) with or without radiation therapy may kill more tumor cells.

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.

What data supports the effectiveness of the drugs used in the Chemotherapy + Radiation for Kidney Cancer (Wilms' Tumor) trial?

Research shows that combining drugs like actinomycin-D, vincristine, and adriamycin with surgery and radiation has improved survival rates in children with advanced Wilms' tumor. The combination of these drugs has been more effective than using them individually, leading to better outcomes in terms of survival and disease-free periods. ^{1 2 3 4 5}

Is the chemotherapy and radiation treatment for Wilms' tumor generally safe for humans?

The treatment involving chemotherapy drugs like actinomycin-D, vincristine, and Adriamycin has been studied in Wilms' tumor and other cancers, showing mild to moderate side effects, with no significant cardiac toxicity observed in some studies. These drugs have been used safely in humans, although side effects like myelosuppression (reduced bone marrow activity) and skin or mucosal toxicities may occur. ^{1 6 7 8 9}

What makes the chemotherapy and radiation treatment for Wilms' tumor unique?

This treatment combines multiple chemotherapy drugs with radiation, which is different from standard treatments that often use fewer drugs or omit radiation in certain cases. The inclusion of drugs like cyclophosphamide and liposomal vincristine sulfate, along with the timing of chemotherapy before radiation, aims to enhance effectiveness against the tumor. ^{1 4 5 10 11}

Research Team

David B Dix

Principal Investigator

Children's Oncology Group

Eligibility Criteria

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

Fertile patients must use effective contraception

I can perform most of my daily activities without assistance.

Not pregnant or nursing

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of combination chemotherapy in Wistar/Furth rats bearing transplantable Wilms' tumor. [2018]

3. Germany pubmed.ncbi.nlm.nih.gov

The use of four-drug combination chemotherapy (D.A.V.E.) in the treatment of advanced Wilms' tumour. [2019]

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

Treatment of Wilms' tumor. Results of the Third National Wilms' Tumor Study. [2022]

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

Preoperative chemotherapy with doxorubicin in Wilms tumor. [2015]

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

Phase II study of 4'-epi-doxorubicin in metastatic renal cancer. [2013]

7. Germany pubmed.ncbi.nlm.nih.gov

Liposomal daunorubicin (DaunoXome) for treatment of poor-risk acute leukemia. [2013]

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

Phase II trial of liposomal encapsulated doxorubicin in patients with advanced renal cell carcinoma. [2019]

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

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

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

Radiotherapy omitted in the treatment of selected children under 3 years of age with stage III favorable histology Wilms tumor. [2019]

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

A murine Wilms' tumor as a model for chemotherapy and radiotherapy. [2019]