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New treatment option for Osteosarcoma
Official title Eflornithine (DFMO) for Ewing Sarcoma and Osteosarcoma
ClinicalTrials.gov ID: NCT07321912
What this study is testing
What is Eflornithine?
Eflornithine is an investigational medicine, given as an once-daily pill taken by mouth, being studied as a potential treatment for osteosarcoma.
Also referred to as DFMO.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 0 to 50
You may be able to join if
- Cohort 1:
- 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...
- 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.
You likely can't join 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...
- 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...
See the full eligibility criteria
Who can join
- Cohort 1:
- 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...
- 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...
- 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...
- OR a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2
- Adequate liver function defined as:
- Total bilirubin ≤1.5 x upper limit of normal (ULN) for age, and
- SGPT (ALT \<3 x upper limit of normal (ULN) for age (except for participants with liver metastasis who may enroll if ALT \< 5 times ULN for age).
- Adequate cardiac function defined as:
- Shortening fraction of ≥27% or
- Ejection fraction of ≥50%
- Participants must have fully recovered from the hematological and bone marrow suppression effects of prior chemotherapy.
- Participants must have a Lansky Play Scale or Karnofsky Performance Scale score of ≥ 60.
- Participants of childbearing potential must have a negative pregnancy test and agree to use an effective birth control method. Participants who are lactating must agree to stop breast-feeding.
- Written informed consent in accordance with institutional and FDA guidelines must be obtained from all participants (or participants' legal representative).
What rules you out
- 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...
- 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)...
- 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...
- 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...
- Contralateral pleural effusion and/or contralateral pleural nodules.
- Distant lymph node involvement.
- Participants with pulmonary nodules are considered to have metastatic disease if the participant has:
- Solitary nodule ≥0.5 cm or multiple nodules of ≥0.3 cm unless lesion is biopsied and negative for tumor;
- Participants with solitary nodule \<0.5 cm or multiple nodules \<0.3 cm are not considered to have lung metastasis unless biopsy documents tumor.
- Bone marrow metastatic disease is based on morphologic evidence of Ewing sarcoma based on H\&E stains. In the absence of morphologic evidence of marrow involvement on H\&E, participants with bone marrow involvement...
- Bone metastasis: This study utilizes whole body FDG-PET scans to screen participants for bone metastases. Areas suspicious for bone metastasis based on FDG-PET scans require confirmatory anatomic imaging with either MRI...
- Participants must have completed 6 cycles of Induction therapy with VDC/IE per US standard of care (including standard modifications). Participants will enroll after the 6th cycle prior to local control. Organ Function...
- Adequate renal function 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...
- 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...
- OR a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2
- Adequate liver function defined as:
- Total bilirubin ≤1.5 x upper limit of normal (ULN) for age, and
- SGPT (ALT \<3 x upper limit of normal (ULN) for age (except for participants with liver metastasis who may enroll if ALT \< 5 times ULN for age).
- Adequate cardiac function defined as:
- Shortening fraction of ≥27% or
- Ejection fraction of ≥50%
- Participants must have fully recovered from the hematological and bone marrow suppression effects of prior chemotherapy.
- Participants must have a Lansky Play Scale or Karnofsky Performance Scale score of ≥ 60.
- Participants of childbearing potential must have a negative pregnancy test and agree to use an effective birth control method. Participants who are lactating must agree to stop breast-feeding.
- Written informed consent in accordance with institutional and FDA guidelines must be obtained from all participants (or participants' legal representative). Exclusion Criteria:
- BSA of \<0.25 m2
- 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.
- Participants with regional node involvement as their only site of disease beyond the primary tumor.
- Participants whose primary tumors arise in the intra-dural soft tissue (e.g. brain and spinal cord).
- Participants with current CNS disease
- 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 3...
- Participants must be less than 30 years of age at enrollment. Diagnosis
- Participants must have histologic diagnosis of osteosarcoma at original diagnosis.
- Participants must have had at least one episode of disease recurrence in the lungs without limitation on number of episodes of recurrence as long as they meet the following criteria:
- Surgical resection of all possible sites of suspected pulmonary metastases in order to achieve a complete remission within 4 weeks prior to study enrollment\
- Pathologic confirmation of metastases from at least one of the resected sites.
- No local recurrence or metastatic disease elsewhere. \ For participants with bilateral pulmonary metastases, resection must be performed from both lungs and the study enrollment must be within 4 weeks from date of the...
- Participants must have a Lansky Play Scale or Karnofsky Performance Scale score of ≥ 60. Timing from Prior Therapy
- Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
- Myelosuppressive anti-cancer therapy: Must not have been received within 2 weeks of study entry (4 weeks if prior nitrosourea).
- Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent.
- Radiation therapy (RT): ≥2 weeks for local palliative RT (small port); ≥6 weeks must have elapsed if prior craniospinal RT or if ≥50% radiation of pelvis; ≥6 weeks must have elapsed if other substantial BM radiation.
- Surgery: ≥2 weeks from last major surgery, including pulmonary metastasectomy, with the exclusion of a central line placement and core needle or small open biopsies. Organ Function Requirements
- Hematological:
- Platelet count ≥50,000/μL without transfusion in last 7 days
- Hgb ≥8.5 without transfusion in last 7 days
- Adequate renal function 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...
- 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...
- OR a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2
- Adequate liver function defined as:
- Total bilirubin ≤1.5 x upper limit of normal (ULN) for age.
- SGPT (ALT \<3 x upper limit of normal (ULN) for age.
- Adequate cardiac function defined as:
- Shortening fraction of ≥27%, or
- Ejection fraction of ≥50%.
- Adequate pulmonary function defined as: o No evidence of dyspnea at rest, no history of exercise intolerance, and a pulse oximetry \>94%.
- Participants of childbearing potential must have a negative pregnancy test and agree to use an effective birth control method. Participants who are lactating must agree to stop breast-feeding.
- Written informed consent in accordance with institutional and FDA guidelines must be obtained from all participants (or participants' legal representative). Exclusion Criteria:
- BSA of \<0.25 m2
- 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.
- Participants with distant bone metastases at original diagnosis or any subsequent relapse (participants with only skip lesions will be eligible).
- Participants with concurrent local and pulmonary recurrence at the time of most recent episode of disease recurrence preceding enrollment. Note: participants who had local recurrence previously that has been treated and...
- Participants with primary refractory disease with progression of the primary tumor on initial therapy.
- Participants with other sites of extra-pulmonary metastases at the time of any episode of disease recurrence preceding enrollment.
- 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 who compliance is likely to be suboptimal. Cohort 4A/B: Inclusion Criteria...
- Participants must have high grade osteosarcoma and received gross total resection prior to start of Cycle 3 MAP therapy. Participants with positive margins are eligible and may receive radiation therapy. This includes...
- The primary tumor was resectable after the initial 2 cycles of MAP chemotherapy.
- Participants must have had a non-contrast chest CT and primary tumor site imaging consisting of an MRI or CT for optimal visualization of primary tumor site prior to local control. Physical scans and scan reports must...
- Participant must have poor response to induction chemotherapy (those with 10% or more viable tumor remaining after surgery) and localized tumor. Cohort B only
- Have an initial diagnosis of high-grade metastatic extremity or axial osteosarcoma resectable by the treating team. o Note: Metastatic pulmonary disease is defined as 3 or more lesions \>5 mm or 1 lesion \>1 cm or...
- No definite progression of metastatic disease and no evidence of new metastatic disease.
- Following definitive primary surgery, complete removal of all metastases or complete removal planned and deemed feasible. Non-Diagnostic Inclusion Criteria, Both Cohorts Age
- Participants must be ≥5 years and ≤40 years on date of diagnostic biopsy. Performance Level
- Participants must have a Lansky Play Scale or Karnofsky Performance Scale score of ≥ 60. Participants whose performance status is adversely affected by a pathologic fracture but who are able to undergo treatment are...
- Participants must have completed standard induction therapy for initial diagnosis osteosarcoma (2 cycles [10weeks]) of MAP, Local control (surgery, assessment of histologic response), and a post-surgery 3rd cycle (5...
- Participants must have adequate renal function defined:
- 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...
- 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...
- OR a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2
- Adequate cardiac function defined as:
- Shortening fraction of ≥28%, or
- Ejection fraction of ≥50%
- Adequate liver function defined as:
- Total bilirubin ≤1.5 x upper limit of normal (ULN) for age
- SGPT (ALT \<3 x upper limit of normal (ULN) for age.
- Participants must have fully recovered from the hematological and bone marrow suppression effects of prior chemotherapy.
- Participants of childbearing potential must have a negative pregnancy test and agree to use an effective birth control method. Participants who are lactating must agree to stop breast-feeding.
- Written informed consent in accordance with institutional and FDA guidelines must be obtained from all participants (or participants' legal representative). Exclusion Criteria:
- BSA of \<0.25 m2
- 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 who compliance is likely to be suboptimal.
The study team makes the final eligibility decision.
Where it's taking place
- Tampa, Florida, United States
- Hershey, Pennsylvania, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 0 years to 50 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Tampa, Florida, United States; Hershey, Pennsylvania, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.