Chemotherapy + Surgery for Kidney Cancer (Wilms Tumor)

Recruiting at 190 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Must not be taking: Aprepitant

Disqualifiers: Chemotherapy, Radiation therapy, 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: 1

249 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial studies how well combination chemotherapy and surgery work in treating young patients with Wilms tumor. Drugs used in chemotherapy 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. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any tumor cells that remain after surgery.

Will I have to stop taking my current medications?

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

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

Research shows that adding chemotherapy drugs like actinomycin-D and vincristine to surgery and radiotherapy has increased survival rates in Wilms tumor patients. Doxorubicin, when combined with these drugs, has been shown to be effective in treating Stage III Wilms tumor. ^{1 2 3 4 5}

Is the chemotherapy and surgery treatment for Wilms tumor generally safe?

The chemotherapy drugs used for Wilms tumor, like vincristine and actinomycin-D, have been associated with some serious side effects, such as veno-occlusive disease (a liver condition) and severe liver toxicity. However, these drugs have been used for a long time and are considered effective, with adjustments made to reduce risks. ^{1 2 3 5 6}

What makes the chemotherapy and surgery treatment for Wilms Tumor unique?

This treatment combines chemotherapy drugs like Dactinomycin, Doxorubicin, and Vincristine with surgery, which is a comprehensive approach targeting Wilms Tumor, a type of kidney cancer in children. The combination of these specific drugs and surgery is designed to maximize the effectiveness of treatment by attacking the cancer cells in multiple ways. ^{7 8 9 10 11}

Research Team

Peter F Ehrlich

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for young patients with Wilms tumor who haven't had chemotherapy or radiation before. They must have normal liver function and heart performance, agree to use contraception if applicable, and not be breastfeeding. Patients need to sign consent forms and meet all study requirements.

Inclusion Criteria

My bilirubin levels are within normal range for my age.

I have not had my kidney removed at diagnosis for specific conditions.

I am of childbearing age and have a negative pregnancy test.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy Induction

Patients receive initial chemotherapy to reduce tumor size and assess feasibility of partial nephrectomy

12 weeks

Weekly visits for chemotherapy administration

Surgery

Definitive surgery is performed, potentially including partial nephrectomy or renal sparing surgery

1 week

1 visit (in-person)

Post-Surgery Chemotherapy and Radiation

Patients receive additional chemotherapy and possibly radiation therapy based on histology and stage

13-19 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Treatment Details

Interventions

• Dactinomycin
• Doxorubicin Hydrochloride
• Radiation Therapy
• Therapeutic Conventional Surgery
• Vincristine Sulfate

Trial Overview The trial tests how well a combination of chemotherapy drugs (Doxorubicin Hydrochloride, Vincristine Sulfate, Dactinomycin) plus surgery works in treating Wilms tumor. The aim is to see if this approach can shrink the tumor before surgery or eliminate remaining cells after.

Participant Groups

Group I: Arm 3 (DHPLN) Experimental Treatment 5 Interventions

Patients with this rare disease are diagnosed based on cross-sectional imaging characteristics and undergo 2 drug chemotherapy (Regimen;VA). Patients are reassessed at 6 weeks and 12 weeks. If disease has responded or stayed stable chemotherapy is completed for 19 weeks (Regimen EE4A). If disease has progress a biopsy is performed to assess histology and adjust therapy based on the biopsy. This therapy may include, nephrectomy, chemotherapy or radiation therapy.

Group II: Arm 2 (Unilateral High Risk tumors bilaterally predisposed) Experimental Treatment 5 Interventions

Patients start with either 2 drug or three drug chemotherapy (Regimen VA, VAD) and are evaluated a 6 and 12 weeks for feasibility of undergoing a partial nephrectomy. At week 12 definitive surgery takes place followed by chemotherapy.

Group III: Arm 1 (Bilateral Wilms Tumors) Experimental Treatment 5 Interventions

Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy.

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

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]

A review of 36 studies on mitomycin C and oxaliplatin used in hyperthermic intraperitoneal chemotherapy (HIPEC) after surgery for colorectal cancer showed that while both agents are safe, there is no clear consensus on which is superior due to study variability and lack of randomized trials.

Oxaliplatin-based HIPEC may result in lower perioperative morbidity compared to mitomycin C, but mitomycin C is considered more cost-effective, highlighting the need for further randomized trials to better understand their comparative effectiveness and impact on patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperthermic Intraperitoneal Chemotherapy with Mitomycin C versus Oxaliplatin after Cytoreductive Surgery for the Treatment of Peritoneal Metastases of Colorectal Cancer Origin. Papageorgopoulou, C., Nikolakopoulos, K., Seretis, C.[2022]

In a study comparing HIPEC with Oxaliplatin (39 patients) and Mitomycin C (MMC, 56 patients) for colorectal cancer peritoneal carcinomatosis, Oxaliplatin patients had a higher extent of disease but less intra-operative blood loss compared to MMC patients.

Despite differences in toxicity, including neutropenia in MMC patients, there was no significant difference in recurrence-free survival (RFS) or overall survival (OS) between the two treatment groups, suggesting that neither agent showed a clear advantage in long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of Oxaliplatin or Mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: a comparative study. Hompes, D., D'Hoore, A., Wolthuis, A., et al.[2022]

References

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

Preoperative chemotherapy with doxorubicin in Wilms tumor. [2015]

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

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

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

Doxorubicin for favorable histology, Stage II-III Wilms tumor: results from the National Wilms Tumor Studies. [2016]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Veno-occlusive disease as a complication of preoperative chemotherapy for Wilms tumor: A clinico-pathological analysis. [2022]

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. England pubmed.ncbi.nlm.nih.gov

Assessment of nephrotoxicity associated with combined cisplatin and mitomycin C usage in laparoscopic hyperthermic intraperitoneal chemotherapy. [2019]

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

Sodium Thiosulfate Reduces Acute Kidney Injury in Patients Undergoing Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy with Cisplatin: A Single-Center Observational Study. [2022]

9. Romania pubmed.ncbi.nlm.nih.gov

Hyperthermic Intraperitoneal Chemotherapy with Mitomycin C versus Oxaliplatin after Cytoreductive Surgery for the Treatment of Peritoneal Metastases of Colorectal Cancer Origin. [2022]

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

Peritoneal Metastases of Colorectal Origin Treated with Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy: The Efficiency of Mitomycin C. [2022]

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

The use of Oxaliplatin or Mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: a comparative study. [2022]