Eflornithine (DFMO) for Ewing Sarcoma and Osteosarcoma

NCT07321912 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BCC023
• Study Type: interventional
• Target: 406
• Locations: 0 countries
• Sites: N/A

Brief Summary

Ewing sarcoma (EWS) and osteosarcoma primarily affect adolescents and young adults. Common treatments include chemotherapy, surgery and radiation, however, there have been few recent advancements in the standard of care. By incorporating eflornithine (DFMO) as an additional therapy and/or maintenance therapy we hope to safely observe improved event-free survival and overall survival. There are 5 cohorts covered under this master protocol.

Conditions

Osteosarcoma; Ewing Sarcoma; Ewing Sarcoma Metastatic

Outcome Measures

Primary Outcomes (5)

• Number of Cohort 1 participants with relapse free survival (RFS) during study

  Cohort 1: To determine if relapse-free survival (RFS) in participants with relapsed or refractory Ewing sarcoma treated with multiagent chemotherapy is improved with the addition of DFMO as compared to historical outcomes of participants treated with the same multiagent chemotherapy without DFMO.

  2 years plus 5 years follow up

• Number of Cohort 2 participants with event-free survival (EFS) during study

  Cohort 2: To determine if event-free survival (EFS) in participants with newly diagnosed metastatic Ewing sarcoma treated with multiagent chemotherapy is improved with the addition of DFMO as compared to historical outcomes of participants treated with the same multiagent chemotherapy without DFMO.

  2 years plus 5 years follow up

• Cohort 3: Number of Cohort 3 participants at 12 months with disease control

  To determine the 12-month disease control rate (DCR) in participants with completely resected recurrent osteosarcoma treated with DFMO as compared to historical controls.

  1 year plus 5 years follow up

• Cohort 4A: Number of Cohort 4A participants with event-free survival (EFS) during study

  Examine whether the addition of DFMO to post-operative chemotherapy with cisplatin, doxorubicin, and methotrexate (MAP) improves the event-free survival (EFS) for participants with osteosarcoma having localized disease with a poor histological response to 10 weeks of pre-operative chemotherapy.

  2 years plus 5 years follow up

• Cohort 4B: Number of Cohort 4B participants with event-free survival (EFS) during study

  Examine whether the addition of DFMO to post-operative chemotherapy with cisplatin, doxorubicin, and methotrexate (MAP) improves the event-free survival (EFS) for participants with osteosarcoma with metastatic disease at diagnosis (Cohort 4B).

  2 years plus 5 years follow up

Secondary Outcomes (2)

• Length of time that participants experience Overall Survival (OS)

  10 Years

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  2 years

Study Arms (5)

Cohort 1: Relapsed or Refractory Ewing Sarcoma Eligible to Receive Local Control

EXPERIMENTAL

DFMO will be administered as concurrent therapy during treatment of Ewing sarcoma. Participants completing treatment without experiencing an analytic event will continue to receive DFMO monotherapy as a maintenance treatment for an additional 24 months.

Drug: Eflornithine; Drug: Topotecan; Drug: Cyclophosphamide

Cohort 2: Ewing Sarcoma Patients who are Metastatic at Diagnosis

EXPERIMENTAL

DFMO will be administered as concurrent therapy during consolidation treatment of metastatic Ewing sarcoma. Participants completing consolidation treatment without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.

Drug: Eflornithine; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Ifosfamide; Drug: Etoposide

Cohort 3: Osteosarcoma with relapse in the lung after resection of lung metastases

EXPERIMENTAL

DFMO will be dosed twice daily for 730 days.

Drug: Eflornithine

Cohort 4A: Osteosarcoma with Poor Response to Induction Therapy at Completion of Local Control

EXPERIMENTAL

DFMO will be administered as concurrent therapy during Cycles 4-6 of post-surgery consolidation. Participants completing MAP without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.

Drug: Eflornithine; Drug: Doxorubicin; Drug: Cisplatin; Drug: Methotrexate

Cohort 4B: Osteosarcoma with Metastatic Disease at Diagnosis at Completion of Local Control

EXPERIMENTAL

DFMO will be administered as concurrent therapy during Cycles 4-6 of post-surgery consolidation. Participants completing MAP without experiencing an analytic event will continue to receive DFMO monotherapy as a post consolidation maintenance treatment for an additional 24 months.

Drug: Eflornithine; Drug: Doxorubicin; Drug: Cisplatin; Drug: Methotrexate

Interventions

Cyclophosphamide DRUG

IV

Cohort 1: Relapsed or Refractory Ewing Sarcoma Eligible to Receive Local Control; Cohort 2: Ewing Sarcoma Patients who are Metastatic at Diagnosis

Vincristine DRUG

IV

Cohort 2: Ewing Sarcoma Patients who are Metastatic at Diagnosis

Doxorubicin DRUG

IV

Cohort 2: Ewing Sarcoma Patients who are Metastatic at Diagnosis; Cohort 4A: Osteosarcoma with Poor Response to Induction Therapy at Completion of Local Control; Cohort 4B: Osteosarcoma with Metastatic Disease at Diagnosis at Completion of Local Control

Ifosfamide DRUG

IV

Cohort 2: Ewing Sarcoma Patients who are Metastatic at Diagnosis

Etoposide DRUG

IV

Cohort 2: Ewing Sarcoma Patients who are Metastatic at Diagnosis

Cisplatin DRUG

IV

Cohort 4A: Osteosarcoma with Poor Response to Induction Therapy at Completion of Local Control; Cohort 4B: Osteosarcoma with Metastatic Disease at Diagnosis at Completion of Local Control

Methotrexate DRUG

IV

Cohort 4A: Osteosarcoma with Poor Response to Induction Therapy at Completion of Local Control; Cohort 4B: Osteosarcoma with Metastatic Disease at Diagnosis at Completion of Local Control

Eflornithine DRUG

Oral twice daily

Also known as: DFMO

Cohort 1: Relapsed or Refractory Ewing Sarcoma Eligible to Receive Local Control; Cohort 2: Ewing Sarcoma Patients who are Metastatic at Diagnosis; Cohort 3: Osteosarcoma with relapse in the lung after resection of lung metastases; Cohort 4A: Osteosarcoma with Poor Response to Induction Therapy at Completion of Local Control; Cohort 4B: Osteosarcoma with Metastatic Disease at Diagnosis at Completion of Local Control

Topotecan DRUG

IV

Cohort 1: Relapsed or Refractory Ewing Sarcoma Eligible to Receive Local Control

Eligibility Criteria

• Age: 0 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants must be ≤50 years of age at enrollment.
• Histologically confirmed Ewing sarcoma that is refractory or in first or subsequent relapse. Histological confirmation either at initial diagnosis or disease progression.
• Relapsed: Participants that have achieved CR at any point and then relapsed following/during standard of care therapy.
• Refractory: Participants that failed to achieve CR after standard of care therapy or having progressed during standard of care therapy.
• Note: Standard of care therapy for Ewing sarcoma includes multi-agent chemotherapy with local control consisting of either surgery and/or radiation therapy.
• Extent of disease is judged by treating team to be amenable to the delivery of definitive local control (either definitive radiation, surgery, or a combination of these) at the time of study enrollment (to be completed after protocol defined Cycle 2).
• Participants may enroll anytime during Cycle 1 or 2, prior to local control, as long as they received the same treatment during Cycle 1 and 2 as prescribed in this protocol.
• Relapsed or refractory disease, including at least one of the following:
• Tumor by CT or MRI
• FDG-PET that is positive for disease
• Bone Marrow biopsy/aspirate that is positive for disease
• Organ Function Requirements:
• Participants must have adequate renal function as defined as:
• For participants \< 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Bedside Schwartz equation is: \[(0.413) X (Height in cm)\] / SCr
• For participants ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Cockcroft and Gault formula is: \[(140-age) x (Wt in kg) x (0.85 if female)\] / (72 x SCr)

You may not qualify if:

• BSA of \<0.25 m2
• Participants with current CNS disease.
• Investigational Drugs: Participants who are currently receiving another investigational drug are excluded from participation.
• Anti-cancer Agents: Participants who are currently receiving other anticancer agents are not eligible.
• Infection: Participants who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
• Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.
• Cohort 2:
• Age
• Participants must be ≤50 years of age at enrollment.
• Note:
• Infants and small children are eligible for this study, however, the treating physicians and family must be prepared to deliver adequate local control as required in this study (see BCC Surgical and Imaging Guidelines).
• Diagnosis
• Participants with histologic diagnosis (by institutional pathologist) of newly diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) arising from bone or soft tissue and with metastatic disease involving lung, bone, bone marrow, or other metastatic site.
• For the purpose of this study, metastatic disease is defined as one or more of the following:
• Lesions which are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a bone or body cavity with the primary tumor. Skip lesions in the same bone as the primary tumor do not constitute metastatic disease. Skip lesions in an adjacent bone are considered bone metastases. If there is any doubt whether lesions are metastatic, a biopsy of those lesions should be performed.

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• USWM, LLC (dba US WorldMeds): collaborator

Related Links

• Beat Childhood Cancer Research Consortium website

MeSH Terms

Conditions

Osteosarcoma; Sarcoma, Ewing

Interventions

Eflornithine; Topotecan; Cyclophosphamide; Vincristine; Doxorubicin; Ifosfamide; Etoposide; Cisplatin; Methotrexate

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Ornithine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Camptothecin; Alkaloids; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Oxazines; Heterocyclic Compounds, 1-Ring; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Aminopterin; Pterins; Pteridines

Study Officials

• Giselle SaulnierSholler, MD

  Penn State Health Children's Hospital

  STUDY CHAIR

Central Study Contacts

BCC Enroll

CONTACT

7175310003; BCCEnroll@pennstatehealth.psu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Beat Childhood Cancer Chair

Study Record Dates

• First Submitted: January 5, 2026
• First Posted: January 7, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): April 1, 2036
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share