DFMO Maintenance for Patients With Relapsed/Refractory Ewing Sarcoma or Osteosarcoma (DFMO)

The purpose of this study is to determine the feasibility of administering DL-alpha-difluoromethylornithine (DFMO) to patients with relapsed Ewing sarcoma and osteosarcoma who have completed all planned therapy and have no evidence of disease.

Study Overview

• Status: Recruiting
• Conditions: Osteosarcoma Recurrent; Ewing's Tumor Recurrent
• Intervention / Treatment: Drug: DFMO

Detailed Description

Approximately 30-35% of patients diagnosed with osteosarcoma or Ewing sarcoma will develop relapsed/refractory disease and carry a very poor prognosis. DL-alpha-difluoromethylornithine, commonly known as DFMO or eflornithine, is a synthetic analog of the amino acid ornithine. DFMO has been studied in a number of different cancers as either a therapeutic or a chemopreventative agent and is now FDA approved to reduce the risk of relapse in patients with newly diagnosed high-risk neuroblastoma. As DFMO has now been given to over 100 children with metastatic cancer, dosing and safety in this population is well established. Given the stagnant survival rates for children, adolescents, and young adults with relapsed Ewing sarcoma and osteosarcoma over the past few decades, this study will explore the feasibility of using DFMO in patients with relapsed osteosarcoma and relapsed Ewing sarcoma who are without any evidence of disease at the end of therapy in order to prevent disease recurrence.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Rebecca Zylber, MSN; Phone Number: 718-741-2356; Email: rzylber@montefiore.org
• Study Contact Backup: Name: Lara Fabish, MSN; Phone Number: 718-741-2356; Email: lfabish@montefiore.org

Study Locations

• United States
  • New York
    • The Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medical Center
      • Principal Investigator: Alice Lee, MD
      • Contact: Rebecca Zylber; Phone Number: 718-741-2356; Email: rzylber@montefiore.org
      • Contact: Lara Fabish; Email: lfabish@montefiore.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients < 40 years of age at the time of enrollment
• Diagnosis of relapsed osteosarcoma or relapsed Ewing sarcoma who have completed all planned therapy for their relapse, as described in the protocol, and have no evidence of disease
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2
• Myelosuppressive chemotherapy: At least 14 days must have elapsed since completion of myelosuppressive therapy
• Monoclonal antibodies: At least 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to Grade < 2
• Biologic therapy (defined as anti-cancer agents not known to be myelosuppressive): At least 7 days after the last dose of agent
• Radiation therapy: At least 14 days must have elapsed after local External Beam Radiation Therapy (XRT), at least 90 days after Total Body Irradiation (TBI), craniospinal XRT or if radiation to greater than 50% of the pelvis, and at least 42 days if other substantial bone marrow radiation
• Adequate bone marrow function defined as:
• Peripheral absolute neutrophil count (ANC) greater or equal to 750/microliter
• Platelet count greater or equal to 75,000/microliter (transfusion independent)
• Adequate renal function defined by serum creatinine based on age and gender (see protocol)
• Adequate liver function defined as:
• Total bilirubin ≤ 1.5 x the upper limit of normal (ULN) for age AND
• SGPT (ALT) ≤ 5.0 x ULN for age. For this study the ULN is 45 U/L

Exclusion Criteria:

• Pregnant or breastfeeding females. Men and women of childbearing potential and their partners must agree to use adequate contraception while enrolled on this study. Based on the teratogenic potential of the agent, pregnant women will be excluded from this study. Because of potential risks to breastfed infants due to drug metabolites that could be excreted in breast milk, female patients who are lactating must agree to stop breastfeeding or will otherwise be excluded from this study. Females of childbearing potential must have a negative pregnancy test to be eligible for this study
• Patients must not have an uncontrolled infection
• Patients with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of study agents or to significantly increase the severity of the toxicities experienced from study treatment are not eligible

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment with DFMO; DFMO will be administered orally every 12 hours in 28-day cycles at the FDA approved dosages based on the patient's body surface area (BSA). DFMO tablets are 192 mg.; Patients with a BSA < 1.5 m^2 will take 768 mg (four tablets) orally twice a day.; Patients with a BSA 0.75 to 1.5 m^2 will take 576 mg (three tablets) orally twice a day.; Patients with a BSA of 0.5 to < 0.75 m^2 will take 384 mg (two tablets) orally twice a day.; Patients with a BSA of 0.25 to < 0.5 m^2 will take 192 mg (one tablet) orally twice a day.

Drug: DFMO; DFMO dose will be calculated based on the BSA measured within 14 days prior to the beginning of each cycle. Tablets may be swallowed whole, chewed, or crushed and mixed with soft food or liquid.; Other Names: Difluoromethylornithine; iWilfin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of Administering DFMO	Feasibility will be defined as the ability to successfully administer DFMO to at least 80% of subjects who initiate therapy until either disease recurrence or completion of the maximally allowed duration of therapy. Results will be summarized using basic descriptive statistics.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Free Survival	The number/percentage of participants with event-free survival (EFS) at 2 years will be determined. Event-free survival will be defined as the time from diagnosis until drug discontinuation, disease progression, recurrence at any site, secondary malignancy, death from any cause, or last follow-up, whichever is observed first.	Up to 2 years

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Collaborators: Johns Hopkins University
• Investigators: Principal Investigator: Alice Lee, MD, Montefiore Medical Center

Publications and helpful links

General Publications

• Lagmay JP, Krailo MD, Dang H, Kim A, Hawkins DS, Beaty O 3rd, Widemann BC, Zwerdling T, Bomgaars L, Langevin AM, Grier HE, Weigel B, Blaney SM, Gorlick R, Janeway KA. Outcome of Patients With Recurrent Osteosarcoma Enrolled in Seven Phase II Trials Through Children's Cancer Group, Pediatric Oncology Group, and Children's Oncology Group: Learning From the Past to Move Forward. J Clin Oncol. 2016 Sep 1;34(25):3031-8. doi: 10.1200/JCO.2015.65.5381. Epub 2016 Jul 11.
• Collier AB 3rd, Krailo MD, Dang HM, DuBois SG, Hawkins DS, Bernstein ML, Bomgaars LR, Reed DR, Gorlick RG, Janeway KA. Outcome of patients with relapsed or progressive Ewing sarcoma enrolled on cooperative group phase 2 clinical trials: A report from the Children's Oncology Group. Pediatr Blood Cancer. 2021 Dec;68(12):e29333. doi: 10.1002/pbc.29333. Epub 2021 Sep 8.

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2025
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2030

Study Registration Dates

• First Submitted: March 19, 2025
• First Submitted That Met QC Criteria: March 19, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Recurrence; Sarcoma, Ewing; Osteosarcoma; Amino Acids, Peptides, and Proteins; Amino Acids; Amino Acids, Basic; Amino Acids, Diamino; Ornithine; Eflornithine
• Other Study ID Numbers: 2024-16461

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No