Brief Summary
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.
Brief Title
DFMO Maintenance for Patients With Relapsed/Refractory Ewing Sarcoma or Osteosarcoma
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
718-741-2356
Central Contact Email
rzylber@montefiore.org
Central Contact Role
Contact
Central Contact Phone
718-741-2356
Central Contact Email
lfabish@montefiore.org
Completion Date
Completion Date Type
Estimated
Conditions
Osteosarcoma Recurrent
Ewing's Tumor Recurrent
Eligibility Criteria
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
* 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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
39 Years
NCT Id
NCT06892678
Org Class
Other
Org Full Name
Montefiore Medical Center
Org Study Id
2024-16461
Overall Status
Recruiting
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
DFMO Maintenance for Patients With Relapsed/Refractory Ewing Sarcoma or Osteosarcoma
Primary Outcomes
Outcome Description
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.
Outcome Measure
Feasibility of Administering DFMO
Outcome Time Frame
Up to 2 years
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Up to 2 years
Outcome Measure
Event Free Survival
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Maximum Age Number (converted to Years and rounded down)
39
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Alice Lee
Investigator Email
alee5@montefiore.org
Investigator Department
Pediatrics
Investigator Division
Pediatric Hematology-Oncology
Investigator Sponsor Organization
Montefiore
Study Department
Pediatrics
Study Division
Please Specify
MeSH Terms
EFLORNITHINE
ORNITHINE
AMINO ACIDS, BASIC
AMINO ACIDS
AMINO ACIDS, PEPTIDES, AND PROTEINS
AMINO ACIDS, DIAMINO