Chemotherapy +/− Radiation for Kidney Cancer

Recruiting at 329 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Disqualifiers: Pregnancy, Prior chemotherapy, 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: 25 weeks

808 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial is studying vincristine, dactinomycin, and doxorubicin with or without radiation therapy or observation only to see how well they work in treating patients undergoing surgery for newly diagnosed stage I, stage II, or stage III Wilms' tumor. Drugs used in chemotherapy, such as vincristine, dactinomycin, and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors.Giving these treatments after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient.

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

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drugs used in the Chemotherapy +/− Radiation for Kidney Cancer trial?

Research on Wilms' tumor shows that the combination of actinomycin-D and vincristine significantly improves survival rates compared to using each drug alone. Additionally, doxorubicin has shown promise in clinical trials, suggesting these drugs may be effective in treating kidney cancer as well. ^{1 2 3 4 5}

Is the combination of chemotherapy and radiation generally safe for humans?

Some studies have shown that certain chemotherapy drugs like dactinomycin and vincristine can cause severe liver damage, especially at higher doses. Additionally, dactinomycin can increase the risk of lung damage when used with radiation therapy. These findings suggest that while these treatments can be effective, they also carry significant risks that need to be carefully managed. ^{6 7 8 9 10}

How does the drug combination of Dactinomycin and Vincristine Sulfate differ from other treatments for kidney cancer?

The combination of Dactinomycin and Vincristine Sulfate is unique because it has been shown to be more effective than using either drug alone, particularly in treating Wilms' tumor, a type of kidney cancer. This combination is under study for its potential to improve outcomes when used with or without radiation therapy, offering a novel approach compared to standard treatments. ^{1 2 11 12 13}

Research Team

Elizabeth A Mullen

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for young patients who've had surgery for a newly diagnosed Wilms' tumor, which is a type of kidney cancer. It's open to those with stage I-III disease, under 30 years old, and without certain genetic syndromes or bilateral tumors. Patients must not be pregnant, should use contraception if fertile, and have not received prior tumor treatments.

Inclusion Criteria

My tumor has a measurable weight.

My condition fits into one of the required disease categories.

I have not had chemotherapy or radiotherapy for my tumor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Patients undergo nephrectomy or biopsy as part of the initial treatment procedure

1 week

Treatment

Patients receive chemotherapy with vincristine, dactinomycin, and doxorubicin, and may undergo radiotherapy

25 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 years

Treatment Details

Interventions

• 3-dimensional conformal radiation therapy
• 3-Dimensional Conformal Radiation Therapy
• Dactinomycin
• Doxorubicin Hydrochloride
• Therapeutic Conventional Surgery
• Vincristine Sulfate

Trial Overview The study tests the effectiveness of chemotherapy drugs vincristine, dactinomycin, and doxorubicin after surgery. Some patients may also receive radiation therapy or just observation. The goal is to see if these treatments can eliminate any remaining cancer cells post-surgery.

Participant Groups

Group I: Stratum III (standard-risk, stage III) Experimental Treatment 11 Interventions

Patients undergo nephrectomy, if feasible, or biopsy. For patients who undergo biopsy only, definitive surgery is undertaken at week 7 or 13. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1 every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 dose of doxorubicin hydrochloride. Patients undergo radiotherapy over 5-7 days after nephrectomy. Treatment continues for up to 25 weeks. Additionally, patients undergo chest X-ray, CT or MRI, ultrasound, echocardiography, and blood sample collection throughout the study.

Group II: Stratum II (standard-risk, stage I or II) Experimental Treatment 11 Interventions

Patients undergo nephrectomy. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1, every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 doses of doxorubicin. Treatment continues for up to 25 weeks. Additionally, patients undergo chest X-ray, CT or MRI, ultrasound, echocardiography, and blood sample collection throughout the study.

Group III: Stratum I (very low-risk disease) Experimental Treatment 11 Interventions

Patients undergo nephrectomy only. If they meet criteria, they are then observed periodically for 5 years. Patients with recurrent disease undergo surgery (immediate or delayed) and receive chemotherapy as in stratum III. Patients with no metachronous renal disease receive radiotherapy. Patients with metachronous disease undergo renal-sparing surgery and chemotherapy as in stratum III, but no radiotherapy. Treatment continues for up to 25 weeks. Additionally, patients undergo chest X-ray, CT or MRI, ultrasound, echocardiography, and blood sample collection throughout the study.

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

Approved in United States as Cosmegen for:

• Rhabdomyosarcoma
• Ewing sarcoma
• Wilms tumor
• Troophoblastic neoplasm

Approved in European Union as Actinomycin D for:

• Rhabdomyosarcoma
• Ewing sarcoma
• Wilms tumor
• Troophoblastic neoplasm

Approved in Canada as Cosmegen for:

• Rhabdomyosarcoma
• Ewing sarcoma
• Wilms tumor
• Troophoblastic neoplasm

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]

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

The effects of chemotherapy on the Wistar-Furth Wilms' Tumor. [2015]

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

Treatment of children with stages II to IV anaplastic Wilms' tumor: a report from the National Wilms' Tumor Study Group. [2017]

5. Germany pubmed.ncbi.nlm.nih.gov

Dexverapamil to modulate vinblastine resistance in metastatic renal cell carcinoma. [2019]

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

Severe hepatic toxicity after treatment with single-dose dactinomycin and vincristine. A report of the National Wilms' Tumor Study. [2019]

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

Severe hepatic toxicity after treatment with vincristine and dactinomycin using single-dose or divided-dose schedules: a report from the National Wilms' Tumor Study. [2017]

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

A phase II study of rebeccamycin analog (NSC-655649) in metastatic renal cell cancer. [2019]

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

Tolerance to single-dose dactinomycin in combination chemotherapy for solid tumors. [2015]

10. England pubmed.ncbi.nlm.nih.gov

Dactinomycin potentiation of radiation pneumonitis: a forgotten interaction. [2019]

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

Combined intra-arterial actinomycin D and radiation therapy for surgically unresectable hypernephroma. [2019]

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

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

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

Preoperative chemotherapy with doxorubicin in Wilms tumor. [2015]