Vincristine + Irinotecan + Regorafenib for Ewing Sarcoma

Recruiting at 4 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Children's Oncology Group

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors

Disqualifiers: Charcot-Marie-Tooth, Organ allograft, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

437 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of drugs—vincristine, irinotecan, and regorafenib—to determine if they outperform the usual treatment for Ewing sarcoma and similar cancers that have metastasized. The goal is to assess whether this new combination can more effectively halt the growth and spread of cancer cells compared to current treatments. Individuals recently diagnosed with Ewing sarcoma or similar cancers that have spread beyond the original site may be suitable candidates for this study. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to advancements in cancer treatment.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that patients receiving strong CYP3A4 inducers or inhibitors are excluded, which might affect some medications you are taking. It's best to discuss your current medications with the trial team to see if they are compatible.

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

Research has shown that the combination of vincristine, irinotecan, and regorafenib has been studied in children with cancer. These studies indicate that the combination can work against tumors. However, like many cancer treatments, it has some side effects.

One study found a response rate of 38% for this combination, meaning about 38% of patients experienced tumor shrinkage or halted growth temporarily. In terms of safety, the study did not report any unexpected severe side effects, suggesting the treatment was generally well-tolerated.

Since this trial is in phase 2/3, earlier studies have demonstrated that the treatment is safe enough for testing on more people. This stage of research examines the treatment's effectiveness and safety in larger groups.

Vincristine, irinotecan, and regorafenib have been used in other cancer treatments, providing some reassurance about their safety. However, each new combination can have different effects. It is important to consult a healthcare provider about potential risks and benefits before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Vincristine, Irinotecan, and Regorafenib for treating Ewing Sarcoma because it introduces a novel approach compared to existing treatments. Unlike standard chemotherapy options, which primarily focus on stopping cancer cells from dividing, Regorafenib targets specific proteins that help cancer cells grow and spread, offering a new mechanism of action. Additionally, the combination with Irinotecan and Vincristine aims to enhance the treatment's effectiveness by attacking the cancer from multiple angles, potentially improving outcomes for patients. This multi-pronged approach is what makes this treatment stand out in the quest to battle Ewing Sarcoma.

What evidence suggests that this trial's treatments could be effective for Ewing sarcoma?

Research has shown that a combination of three drugs—vincristine, irinotecan, and regorafenib—may be promising for treating Ewing sarcoma, a type of cancer. In this trial, participants in one arm will receive this combination. Studies have found that this combination works in children, which is encouraging. Specifically, one study found that 38% of patients experienced tumor shrinkage, suggesting that the treatment might help stop cancer growth. Since Ewing sarcoma is difficult to treat, especially when it spreads, these results are significant. Overall, this combination attacks cancer cells in several ways, potentially increasing its effectiveness. ^{2 4 5 6 7}

Who Is on the Research Team?

Bhuvana A Setty

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for patients aged 1 month to 50 years with suspected or confirmed Ewing sarcoma or round cell sarcomas, including those with specific molecular alterations. Participants must be enrolled in the Molecular Characterization Initiative before joining this study.

Inclusion Criteria

My diagnosis is round cell sarcoma.

My cancer is a type of round cell sarcoma.

I am enrolled in APEC14B1 and agreed to the Molecular Characterization Initiative.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide over 6 cycles, followed by surgery or radiation therapy

12 weeks

Multiple visits for each cycle

Consolidation I

Patients receive vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide over 4 cycles

8 weeks

Multiple visits for each cycle

Consolidation II

Patients are randomized to Regimen A or B, receiving vincristine, cyclophosphamide, ifosfamide, etoposide, irinotecan, and regorafenib over 6-7 cycles

12-14 weeks

Multiple visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Every 3 months for years 1-2, every 6 months for years 3-4, then annually for years 5-10

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Etoposide
• Ifosfamide
• Irinotecan Hydrochloride
• Regorafenib
• Vincristine Sulfate

Trial Overview The trial compares a new drug combo (VIrR/VDC/IE) against the usual treatment (VDC/IE) for metastatic Ewing sarcoma. VIrR includes vincristine, irinotecan, and regorafenib—drugs that inhibit tumor growth by various mechanisms.

How Is the Trial Designed?

Group I: Regimen B (VIrR/VDC/IE) Experimental Treatment 19 Interventions

See Detailed Description

Group II: Regimen A (VDC/IE) Active Control 17 Interventions

See Detailed description

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10618645/

Regorafenib plus Vincristine and Irinotecan in Pediatric ... Our results show that the combination of regorafenib with standard doses of vincristine and irinotecan exhibits clinical activity in pediatric ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06820957

NCT06820957 | Testing a New Combination of Anti-cancer ... To determine if the event-free survival (EFS) in patients with newly diagnosed metastatic Ewing sarcoma is improved when treated with vincristine-irinotecan- ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.10507

Phase I study of regorafenib in combination with vincristine ... The response rate was 38%, including 1 complete (RMS) and 7 partial responders (5 RMS, 2 Ewing sarcoma); 3 of whom had prior irinotecan. Six (4 ...

4. aacrjournals.org aacrjournals.org/clincancerres/article-pdf/29/21/4341/3375061/4341.pdf

Regorafenib plus Vincristine and Irinotecan in Pediatric ... Results: We enrolled 21 patients [median age, 10 years; 12, RMS;. 5, Ewing sarcoma (EWS)]. The MTD/RP2D of regorafenib in the sequential ...

5. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.35537

Consensus recommendations for systemic therapies in the ... Treatment of relapsed/refractory ES (RR-ES) remains a clinical challenge; the 5-year survival rate is less than 15%, and the majority of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37606641/

Regorafenib plus Vincristine and Irinotecan in Pediatric ... Median progression-free survival was 7.0 months [95% confidence interval (CI), 2.9-14.8] and median overall survival was 8.7 months (95% CI, 5.5 ...

7. aacrjournals.org aacrjournals.org/clincancerres/article/29/21/4341/729637/Regorafenib-plus-Vincristine-and-Irinotecan-in

Regorafenib plus Vincristine and Irinotecan in Pediatric ... Our results show that the combination of regorafenib with standard doses of vincristine and irinotecan exhibits clinical activity in pediatric patients with RMS ...