Chemotherapy + Surgery for Kidney Cancer (Wilms Tumor)

Not currently recruiting at 201 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well a combination of chemotherapy drugs and surgery can treat young patients with Wilms tumor, a type of kidney cancer. The chemotherapy drugs—Dactinomycin, Doxorubicin Hydrochloride, and Vincristine Sulfate—work together to shrink the tumor before surgery or eliminate any remaining cancer cells afterward. Participants who might be suitable include those with Wilms tumor, especially children with certain genetic conditions or tumors in both kidneys. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer 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 it does mention that 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 combination of vincristine, dactinomycin, and doxorubicin has been safely used in past studies to treat Wilms tumor and other childhood kidney cancers. These drugs are well-known in cancer treatment and have FDA approval for this purpose.

Studies have found that this combination is generally well-tolerated, with most patients not experiencing severe side effects. This makes it a recommended option for further research in similar conditions. Specifically, vincristine and dactinomycin have been used together to treat Wilms tumor, focusing on improving survival rates.

While all treatments can have side effects, past research supports the safety and effectiveness of these drugs in similar clinical settings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Wilms Tumor because they offer a more tailored approach based on tumor characteristics and patient response. Unlike the standard of care, which often involves a one-size-fits-all chemotherapy regimen, these treatments allow for adjustments after initial chemotherapy based on how the tumor responds, potentially leading to more effective and less invasive treatment options. In particular, the use of regimens like VAD (vincristine, dactinomycin, and doxorubicin) and VA (vincristine and dactinomycin) in combination with partial nephrectomy or renal-sparing surgery is designed to preserve kidney function, which is a significant advancement in managing this condition. Furthermore, researchers are keen to explore how these regimens might minimize the need for more aggressive interventions, such as radiation, based on histological findings.

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

Research has shown that a combination of chemotherapy drugs, including vincristine, dactinomycin, and doxorubicin, effectively treats Wilms tumor. In this trial, participants in different arms will receive varying combinations of these drugs. One study found that over 91% of patients treated with this combination did not experience a return of cancer within two years. Another study showed that the overall survival rate at five years was nearly 99% with similar treatments. Vincristine and dactinomycin work particularly well together, leading to better results than when used separately. These drugs stop the tumor from growing by killing cancer cells or preventing them from spreading. ^{1 6 7 8 9}

Who Is on the Research Team?

Peter F Ehrlich

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4054506/

Innovations in the management of Wilms' tumor - PMC Vincristine and dactinomycin are more effective in combination than individually. NWTS-2, Vincristine/dactinomycin comparably effective when given for 6 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9440748/

a report from the National Wilms' Tumor Study Group - PubMed Results: The 2-year relapse-free survival (RFS) rates for LR patients were 91.3% for 544 randomized to treatment with PI and 91.4% for 556 randomized to ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00945009?term=AREA%5BConditionSearch%5D(%22Wilms%20Tumor%22)&rank=3

Combination Chemotherapy and Surgery in Treating ... To improve 4-year event-free survival (EFS) to 73% for young patients with bilateral Wilms tumor (BWT). II. To prevent complete removal of at least one kidney ...

4. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT00379340

UCSF Wilms Tumor Trial → Combination Chemotherapy ... This phase III trial is studying how well combination chemotherapy with or without radiation therapy works in treating young patients with newly diagnosed ...

5. jnccn.org jnccn.org/downloadpdf/journals/jnccn/19/8/article-p945.pdf

Wilms Tumor (Nephroblastoma), Version 2.2021 Excellent outcomes have been achieved for all stages of FHWT, including those patients with higher stage disease, unfavorable bio- markers, and adverse clinical ...

6. sciencedirect.com sciencedirect.com/science/article/pii/0360301676900444

Management of Wilms' tumor with particular emphasis on ... A survey of our experience with 35 children with Wilms' tumor treated between 1960 and 1971, revealed an absolute 2-, 3- and 5-year survival of 63, ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00352534?tab=table

Vincristine, Dactinomycin, and Doxorubicin With or Without ... This phase III trial is studying vincristine, dactinomycin, and doxorubicin with or without radiation therapy or observation only to see how well they work ...

8. redjournal.org redjournal.org/article/0360-3016(76)90044-4/fulltext

Management of Wilms' tumor with particular emphasis on ... A survey of our experience with 35 children with Wilms' tumor treated between 1960 and 1971, revealed an absolute 2-, 3- and 5-year survival of 63, ...

9. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/658675

Role of Dactinomycin in the Improved Survival of Children ... Thirty consecutive cases of histologically proved Wilms' tumor followed for a minimum of two years have been reviewed. The overall survival rate was 70%,