Combination Chemotherapy for Ewing Sarcoma

Not currently recruiting at 267 trial locations
Age: < 65
Sex: Any
Trial Phase: Phase 3
Sponsor: Children's Oncology Group
No Placebo GroupAll 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 DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine if adding a new chemotherapy drug, topotecan hydrochloride, to a standard 5-drug treatment improves outcomes for individuals with Ewing sarcoma, a type of bone or soft tissue cancer that hasn't spread. Participants are divided into two groups: one receives the standard treatment, while the other receives the standard treatment plus topotecan hydrochloride. The trial seeks individuals with newly diagnosed, non-metastatic Ewing sarcoma or related tumors who have not yet received other cancer treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking cancer treatment advancements.

Do I need to stop my current medications to join the trial?

The trial does not specify whether you need to stop taking your current medications. However, since no prior chemotherapy or radiation therapy is allowed, you may need to discuss your current medications with the trial team to ensure they don't conflict with the study requirements.

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

Research has shown that the usual chemotherapy for Ewing sarcoma, which includes drugs like vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide, is generally well-tolerated. Studies have found this treatment effective and less harmful compared to other options. People of different ages have tolerated these drugs well, although side effects can occur.

Adding topotecan to the treatment has shown promising results in studies. This combination has proven effective with manageable side effects. Patients receiving this treatment have also experienced good outcomes. However, like any chemotherapy, side effects can occur, and individuals may react differently.

In summary, both treatment plans have been extensively studied and are considered safe, with side effects that can usually be managed. It's always important to discuss any concerns with healthcare providers.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these combination chemotherapy treatments for Ewing sarcoma because they integrate topotecan hydrochloride, which is not typically part of standard regimens. Unlike traditional treatments, which primarily rely on drugs like vincristine, doxorubicin, and cyclophosphamide, one unique arm in this study also incorporates topotecan, potentially enhancing the treatment's effectiveness. Additionally, the strategic pairing with dexrazoxane aims to reduce heart-related side effects, a concern with doxorubicin usage. This innovative approach could offer improved outcomes and better manage the condition's challenges.

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

In this trial, patients with localized Ewing sarcoma will receive one of two combination chemotherapy regimens. Arm A includes vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide, which previous studies have shown to effectively control the disease and extend patient survival. Arm B adds topotecan to this combination, and earlier research suggests that this addition may further enhance patient outcomes. The trial evaluates these chemotherapy combinations as strong options for treating Ewing sarcoma.678910

Who Is on the Research Team?

PJ

Patrick J Leavey

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for patients with a new diagnosis of non-metastatic Ewing sarcoma or PNET located outside the brain, without prior treatment. Eligible participants must have proper kidney function, normal bilirubin levels, acceptable liver enzyme counts, and good heart function. Pregnant or breastfeeding women are excluded, as well as those who've had previous cancers treated with chemo or radiation.

Inclusion Criteria

I have been diagnosed with Ewing sarcoma or PNET.
I've only had a biopsy for my cancer, with no chemo or radiation.
My liver function tests are within normal limits.
See 8 more

Exclusion Criteria

I have Ewing Sarcoma as a second cancer and haven't had chemo or radiation for my first cancer.
My lung nodules are larger than specified sizes or biopsied positive for cancer.
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
See 8 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Patients receive a combination of chemotherapy drugs including vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, and etoposide, with additional topotecan hydrochloride in Arm B.

12 weeks
Weekly visits for drug administration

Consolidation Therapy

Continuation of chemotherapy with vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, and etoposide, with additional topotecan hydrochloride in Arm B.

22 weeks
Weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years
Every 3 months for 3 years, then every 6 months for 2 years

What Are the Treatments Tested in This Trial?

Interventions

  • Cyclophosphamide
  • Doxorubicin Hydrochloride
  • Etoposide
  • Ifosfamide
  • Topotecan Hydrochloride
  • Vincristine Sulfate
Trial Overview The study tests if adding topotecan hydrochloride to a standard chemotherapy regimen (vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide and etoposide) improves outcomes in Ewing sarcoma patients. Participants are randomly assigned to receive either the standard treatment alone or with the additional drug.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Arm B (combination chemotherapy, topotecan hydrochloride)Experimental Treatment8 Interventions
Group II: Arm A (combination chemotherapy)Experimental Treatment7 Interventions

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

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Approved in United States as Cytoxan for:
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Approved in European Union as Endoxan for:
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Approved in Canada as Neosar for:
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Approved in Japan as Endoxan for:

Find a Clinic Near You

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

In a study of 110 patients with metastatic Ewing sarcoma or primitive neuroectodermal tumor (PNET), the combination of topotecan and cyclophosphamide showed promising activity, with 21 out of 37 patients achieving partial responses.
Amifostine, intended as a cytoprotective agent, did not provide myeloprotection, and overall survival rates remained unchanged compared to previous studies, indicating that while some treatments showed activity, the prognosis for these patients remains poor.
Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457--a report from the Children's Oncology Group.Bernstein, ML., Devidas, M., Lafreniere, D., et al.[2013]

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/37651654/
Long-Term Outcomes in Patients With Localized Ewing ...Patients were randomly assigned to receive vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide alternating once every 3 weeks ...
Dose intensity and outcomes of VDC/IE chemotherapy for ...Dose intensity and outcomes of VDC/IE chemotherapy for adolescent and adult patients with Ewing's family sarcoma. download. Background: Ewing's family sarcoma ( ...
Localized Adult Ewing Sarcoma (ES): Improved Outcomes ...Localized Adult Ewing Sarcoma (ES): Improved Outcomes With Ifosfamide and Etoposide (IE) Added to Cyclophosphamide, Doxorubicin, and Vincristine (CAV) ...
Addition of Ifosfamide and Etoposide to Standard ...A new drug combination, ifosfamide and etoposide, was highly effective in patients with Ewing's sarcoma or primitive neuroectodermal tumor of bone who had a ...
Localized Adult Ewing Sarcoma: Favorable Outcomes with ...This article evaluates outcomes for adults with localized Ewing sarcoma treated exclusively with cyclophosphamide, doxorubicin, and vincristine followed by ...
Phase III Trial Adding Vincristine-Topotecan ...This trial further validates excellent patient outcomes with interval compressed chemotherapy, a finding also seen in preliminary results comparing interval ...
Efficacy and Safety of the Topotecan–Cyclophosphamide ...In the first-line treatment of metastatic ES, the addition of ifosfamide and etoposide (IE) to a vincristine, doxorubicin, and cyclophosphamide ...
AEWS1031Intergroup Ewing sarcoma study INT-0091 (CCG 7881, POG 8850) demonstrated that a regimen of alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide- ...
Outcomes of Pediatric Patients With Metastatic Ewing...The survival rates of patients with localized ES have increased over time, which is primarily because of the addition of cycles of ifosfamide/etoposide (IE) to ...
1916-Ewing sarcoma VDC (vinCRISTine, DOXORubicin ...PURPOSE: Chemotherapy with alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide cycles and primary tumor treatment with surgery and/or ...
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