[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"ewing-sarcoma-metastatic\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:ewing-sarcoma-metastatic":33},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,49],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":37,"lastUpdatePostDateStruct":38,"startDateStruct":41,"completionDateStruct":43,"leadSponsor":45,"locationsCount":48},"100560022","phase-2-xl092-zanzalintinib-for-the-treatment-of-patients-with-metastatic-or-unresectable-leiomyosarcoma-bone-sarcoma-or-translocation-associated-soft-tissue-sarcoma-100560022",false,"NCT06571734","XL092 (Zanzalintinib) for the Treatment of Patients With Metastatic or Unresectable Leiomyosarcoma, Bone Sarcoma or Translocation-associated Soft Tissue Sarcoma","A Non-Randomized, Open-label Phase II Trial Testing the Activity of XL092 (Zanzalintinib) in Patients With Advanced Leiomyosarcoma, Bone Sarcoma or Translocation-associated Soft Tissue Sarcoma","Inclusion Criteria For Cohort 1 - Leiomyosarcoma:\n\n* Patients must have histologically confirmed leiomyosarcoma that has been clinically determined to be metastatic or unresectable. Pathology must have been reviewed at a National Comprehensive Cancer Network (NCCN) designated cancer center such as Northwestern University's Lurie Cancer Center.\n* Patients must have undergone at least 2 or more lines of antineoplastic treatment, but no more than 2 lines of treatment can be a tyrosine kinase inhibitor (TKI).\n\nInclusion Criteria For Cohort 2 - Bone Sarcoma:\n\n* Patients must have histologically confirmed diagnosis of metastatic or unresectable bone sarcoma. Pathology must have been reviewed at a National Comprehensive Cancer Network (NCCN) designated cancer center such as Northwestern University's Lurie Cancer Center.\n* Patients must have undergone at least 1 line of antineoplastic treatment, but no more than 2 lines of treatment can be a tyrosine kinase inhibitor (TKI).\n\nInclusion Criteria For Cohort 3 - Translocation-associated Soft Tissue Sarcoma:\n\n* Patients must have histologically confirmed diagnosis of metastatic or unresectable translocation-associated soft tissue sarcoma (TAS). Pathology must have been reviewed at a National Comprehensive Cancer Network (NCCN) designated cancer center such as Northwestern University's Lurie Cancer Center.\n* Patients must have undergone greater than 2 lines of antineoplastic treatment, but no more than 2 lines of treatment can be a tyrosine kinase inhibitor (TKI).\n\nInclusion Criteria for All Cohorts\u002FSarcoma Types\n\n* Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.\n* Patients must be aged ≥ 18 years on day of signing any informed consent documents.\n* Patients must exhibit a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale or \\> 70% on the Karnofsky Scale.\n* Absolute neutrophil count (ANC) ≥ 1,500\u002FmcL (without granulocyte colony-stimulating factor support within 21 days of screening sample collection)\n* Hemoglobin (Hgb) ≥ 9 g\u002FdL without transfusion within 21 days of screening laboratory sample collection\n* Platelets (PLT) ≥ 100,000\u002Fmm\\^3 (\\> 100 GI\u002FL) without transfusion within 21 days of screening laboratory sample collection\n* International normalized ratio (INR) ≤ 1.5 ULN and activated partial thromboplastin time (aPTT) ≤ 1.2 x upper limit of normal (ULN)\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal ULN; for patients with Gilbert's disease, total bilirubin ≤ 3 x ULN\n* Alanine aminotransferase (AST) ≤ 3 x institutional ULN\n* Aspartate aminotransferase (ALT) ≤ 3 x institutional ULN\n* Alkaline phosphatase (ALP) ≤ 3 x institutional ULN; for patients with documented bone metastasis, ALP ≤ 5 x ULN\n* Serum creatinine ≤ 1.5 x institutional ULN OR calculated creatinine clearance ≥ 40 mL\u002Fmin ( ≥ 0.67 mL\u002Fsec) using the Cockcroft-Gault equation\n* Creatinine clearance ≥ 40mL\u002Fmin\n* Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg\u002Fmg ( ≤ 113.12 mg\u002Fmmol)\n* Patient of child-bearing potential (POCBP) and any of their partners with sperm-producing reproductive capability must agree to use a highly effective method of contraception throughout the course of the study and for 186 days after the last dose of treatment. Additional contraceptive method, such as a barrier method (e.g., condom) is also required\n* Patients with sperm-producing reproductive capacity (PWSPRC) treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence), with partners of childbearing potential from time of informed consent, for the duration of study participation, and for 96 days following completion of therapy\n* Patients must have ejection fraction \\> 50% by either MUGA scan or echocardiogram.\n* Patients must be capable of understanding and complying with the protocol requirements.\n* Patients must have the ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n* Patients who have received previous treatment with XL092.\n* Patients who have received any type of small-molecule kinase inhibitor (including an investigational kinase inhibitor) within 14 days prior to study day 1 treatment.\n* Patients who have received \\> 2 prior tyrosine kinase inhibitor therapies as anticancer treatments.\n* Patients who have had prior chemotherapy, or radiation therapy within 4 weeks prior to start of study treatment unless they have recovered from their prior therapy (toxicity and\u002For complications) such that they now meet all other eligibility criteria\n* Patients who have received radiation therapy for bone metastasis within 14 days prior to registration\n* Patients who have undergone systemic treatment with radionuclides within 6 weeks (42 days) before first dose of study treatment\n* Patients with clinically relevant complications from prior radiation therapy requiring ongoing therapy, per the opinion of the treating investigator enrolling the patient.\n* Patients with a known prior or concurrent malignancy that is progressing or requires active treatment within 2 years of first dose of study treatment. Note: The following exceptions may be made:\n\n  * For patients with malignancies like basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer; or superficial skin cancers, localized low-grade tumors deemed cured and not treated with systemic therapy, and incidentally diagnosed prostate cancer if assessed as stage ≤ T2N0M0 and Gleason score ≤ 6.\n  * For patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen.\n* Patients with known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and\u002For surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment. Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed. Note: Eligible patients must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.\n* Patients who are on concomitant anticoagulation therapy with oral anticoagulants (e.g., warfarin or direct thrombin and factor Xa inhibitors) and platelet inhibitors (e.g., clopidogrel). Note: Allowed anticoagulants are low-dose aspirin for cardioprotection (per local applicable guidelines) and low molecular weight heparins (LMWH). Therapeutic doses of LMWH are not permitted in patients with brain metastases. Note: Patients must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first study treatment, whichever is longer.\n* Patients who are taking any complementary medications (e.g., herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks (14 days) prior to start of treatment. Note: taking complementary medications to treat symptoms of the cancer is allowed.\n* The patient has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\n\n  * Cardiovascular disorders:\n\n    * Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias (e.g., ventricular flutter, ventricular fibrillation, Torsades de pointes)\n    * Uncontrolled hypertension defined as sustained blood pressure (BP) \\> 140 mm Hg systolic of \\> 90 mm Hg diastolic despite optimal antihypertensive treatment\n    * Stroke (including transient ischemic attack \\[TIA\\]), myocardial infarction, or other clinically significant ischemic events within 12 months prior to first dose of study treatment. Note: Patients who did not require prior anticoagulant therapy may be eligible must be discussed and approved by the principal investigator (PI)\n    * Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous or non-cerebrovascular accident (CVA)\u002FTIA arterial thromboembolic events within 6 months before to first dose of study treatment.\n    * Prior history of myocarditis\n  * Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:\n\n    * Tumors invading the GI tract from external viscera\n    * Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis\n    * Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess must be confirmed prior to first dose of study treatment\n    * Known gastric or esophageal varices\n    * Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months unless cause of obstruction is definitively managed and subject is asymptomatic\n* Patients with clinically significant hematuria, hematemesis, or hemoptysis of \\> 0.5 teaspoon (2.5 mL) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 84 days prior to registration.\n* Symptomatic cavitating pulmonary lesions or endobronchial disease (asymptomatic or radiated lesions allowed).\n* Lesions invading major blood vessel including but not limited to inferior vena cava, pulmonary artery, or aorta.\n\nNote: Patients with intravascular tumor extension (e.g., tumor thrombus in renal vein or inferior vena cava) may be eligible following PI approval\n\n* Patients who are capable of donating eggs for the purpose of reproduction must not do so throughout the course of the study and for 186 days after the last dose of treatment\n* Patients who are capable of donating sperm for the purpose of reproduction must not do so throughout the course of the study and for 96 days after the last dose of treatment\n* Other clinically significant disorders that would preclude safe study participation, including, but not limited to:\n\n  * Active infection requiring systemic treatment. Note: This criterion applies only at enrollment; if a patient develops an infection while on study treatment, they may continue to receive study treatment. Note: prophylactic antibiotic treatment is allowed\n  * Known infection with acute or chronic hepatitis B or C, known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness\n  * Known positive test for or suspected infection with SARS-CoV-2 within one month prior to enrollment. Note: Demonstration that the patient has fully recovered from the infection is required to be eligible for enrollment\n  * Serious non-healing wound\u002Fulcer\u002Fbone fracture. Note: non-healing wounds or ulcers are permitted if they are due to tumor-associated skin lesions\n  * Malabsorption syndrome\n  * Pharmacologically uncompensated, symptomatic hypothyroidism\n  * Moderate to severe hepatic impairment (Child-Pugh B or C)\n  * Requirement for hemodialysis or peritoneal dialysis\n  * History of solid organ or allogenic stem cell transplant\n* Recent surgery within the following parameters:\n\n  * Major surgery (e.g., GI surgery or removal\u002Fbiopsy of brain metastasis) within 8 weeks prior to study treatment\n  * Minor surgery (e.g., simple excision, tooth extraction) within 5 days prior to first dose of study treatment. Note: if a patient has had a recent surgery outside of the proscribed interval, complete wound healing from said surgery must have occurred prior to first dose of study treatment. Note: Fresh tumor biopsies should be performed at least 5 days prior to registration. Patients with clinically relevant ongoing complications from prior surgical procedures, including biopsies, are not eligible\n* Corrected QT interval calculated by the Fridericia formula (QTcF) \\> 480 ms within 14 days per electrocardiogram (ECG) prior to first dose of study treatment Note: Triplicate ECG evaluations will be performed and the average of these 3 consecutive results for QTcF will be used to determine eligibility\n* Patients with any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) grade \\> 1 at baseline from a previous anticancer therapy, with the following exceptions:\n\n  * Alopecia, vitiligo, and the laboratory values\n  * Patients with grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the treating physician\n  * Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with XL092 may be included only after consultation with the principal investigator\n* Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to XL092\n* Patients who are pregnant (positive serum or urine test within 72 hours prior to enrollment) or nursing. Pregnant people are excluded from this study because XL092 is a next-generation tyrosine kinase inhibitor with potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the nursing parent with XL092, breastfeeding should be discontinued if the nursing parent is treated with XL092. Note: If a urine pregnancy test is positive or cannot be confirmed negative, a serum pregnancy test will be required\n* Patients with psychiatric illness\u002Fsocial situations that would limit compliance with study requirements, per the opinion of the treating investigator\n* XL092 is administrated orally; patients who are unable to swallow, retain, and\u002For absorb pills are not eligible for this study\n* Patients who are currently participating in or have participated in a study of an investigational agent or have used an investigational device within 4 weeks prior to the first dose of treatment\n* Other conditions which, in the opinion of the Investigator, would compromise the safety of the patient or the patient's ability to complete the study","ALL","18 Years",{"count":19,"type":20},73,"ESTIMATED","INTERVENTIONAL",[23],"PHASE2","This phase II trial tests how well zanzalintinib (XL092) works in treating patients with leiomyosarcoma that has spread from where it first started to other places in the body (metastatic) or that cannot be removed by surgery (unresectable). Leiomyosarcomas are a type sarcoma that can occur in any location in the body, such as the uterus or in the abdomen. Current standard treatment for leiomyosarcoma only shows a progression-free survival of 4-6 months. XL092, a tyrosine kinase inhibitor, interferes with cell communication and growth and may prevent tumor growth. Giving XL092 may kill more tumor cells in patients with metastatic or unresectable leiomyosarcoma. The trial has now been expanded to treat additional sarcoma types that are sensitive to tyrosine kinase inhibitors (TKIs) such as translocation-associated soft tissue sarcoma (such as synovial sarcoma), and bone sarcoma (including osteosarcoma and Ewing sarcoma).",[26,27,28,29,30,31,32,33,34,35],"Metastatic Leiomyosarcoma","Unresectable Leiomyosarcoma","Bone Sarcoma","Translocation-associated Soft Tissue Sarcoma","Synovial Sarcomas","Osteosarcoma Metastatic","Ewing Sarcoma","Ewing Sarcoma Metastatic","Sarcoma Metastatic","Sarcoma of Bone","RECRUITING","2026-06-16",{"date":39,"type":40},"2026-06-18","ACTUAL",{"date":42,"type":40},"2024-09-19",{"date":44,"type":20},"2033-07-01",{"name":46,"class":47},"Northwestern University","OTHER",1,{"id":50,"slug":51,"hasResults":11,"nctId":52,"briefTitle":53,"officialTitle":54,"acronym":4,"eligibilityCriteria":55,"healthyVolunteers":11,"sex":16,"minAge":56,"maxAge":57,"enrollmentInfo":58,"targetDuration":4,"studyType":21,"phases":60,"briefSummary":61,"conditions":62,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":64,"lastUpdatePostDateStruct":65,"startDateStruct":67,"completionDateStruct":69,"leadSponsor":71,"locationsCount":5},"100617691","phase-2-eflornithine-dfmo-for-ewing-sarcoma-and-osteosarcoma-100617691","NCT07321912","Eflornithine (DFMO) for Ewing Sarcoma and Osteosarcoma","A Phase II Open Label Basket Trial Study Using Eflornithine (DFMO) for Ewing Sarcoma and Osteosarcoma","Cohort 1:\n\nInclusion Criteria:\n\n1. Participants must be ≤50 years of age at enrollment.\n2. Histologically confirmed Ewing sarcoma that is refractory or in first or subsequent relapse. Histological confirmation either at initial diagnosis or disease progression.\n\n   * Relapsed: Participants that have achieved CR at any point and then relapsed following\u002Fduring standard of care therapy.\n   * Refractory: Participants that failed to achieve CR after standard of care therapy or having progressed during standard of care therapy.\n   * Note: Standard of care therapy for Ewing sarcoma includes multi-agent chemotherapy with local control consisting of either surgery and\u002For radiation therapy.\n3. 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).\n4. 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.\n5. Relapsed or refractory disease, including at least one of the following:\n\n   * Tumor by CT or MRI\n   * FDG-PET that is positive for disease\n   * Bone Marrow biopsy\u002Faspirate that is positive for disease\n\n   Organ Function Requirements:\n6. Participants must have adequate renal function as defined as:\n\n   * For participants \\\u003C 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL\u002Fmin\u002F1.73 m2) or via radioisotope GFR of ≥ 70 mL\u002Fmin\u002F1.73 m2. The Bedside Schwartz equation is: \\[(0.413) X (Height in cm)\\] \u002F SCr\n   * For participants ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL\u002Fmin\u002F1.73 m2) or via radioisotope GFR of ≥ 70 mL\u002Fmin\u002F1.73 m2. The Cockcroft and Gault formula is: \\[(140-age) x (Wt in kg) x (0.85 if female)\\] \u002F (72 x SCr)\n   * OR a 24 hour urine Creatinine clearance ≥ 70 mL\u002Fmin\u002F1.73 m2\n7. Adequate liver function defined as:\n\n   1. Total bilirubin ≤1.5 x upper limit of normal (ULN) for age, and\n   2. SGPT (ALT \\\u003C3 x upper limit of normal (ULN) for age (except for participants with liver metastasis who may enroll if ALT \\\u003C 5 times ULN for age).\n8. Adequate cardiac function defined as:\n\n   1. Shortening fraction of ≥27% or\n   2. Ejection fraction of ≥50%\n9. Participants must have fully recovered from the hematological and bone marrow suppression effects of prior chemotherapy.\n10. Participants must have a Lansky Play Scale or Karnofsky Performance Scale score of ≥ 60.\n11. 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.\n12. Written informed consent in accordance with institutional and FDA guidelines must be obtained from all participants (or participants' legal representative).\n\nExclusion Criteria:\n\n1. BSA of \\\u003C0.25 m2\n2. Participants with current CNS disease.\n3. Investigational Drugs: Participants who are currently receiving another investigational drug are excluded from participation.\n4. Anti-cancer Agents: Participants who are currently receiving other anticancer agents are not eligible.\n5. 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.\n6. 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.\n\nCohort 2:\n\nInclusion Criteria:\n\n* Age\n\n  1. Participants must be ≤50 years of age at enrollment.\n\n     Note:\n\n     • 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).\n\n     Diagnosis\n  2. 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.\n\n     For the purpose of this study, metastatic disease is defined as one or more of the following:\n     * 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.\n     * Contralateral pleural effusion and\u002For contralateral pleural nodules.\n     * Distant lymph node involvement.\n     * Participants with pulmonary nodules are considered to have metastatic disease if the participant has:\n\n       * Solitary nodule ≥0.5 cm or multiple nodules of ≥0.3 cm unless lesion is biopsied and negative for tumor;\n       * Participants with solitary nodule \\\u003C0.5 cm or multiple nodules \\\u003C0.3 cm are not considered to have lung metastasis unless biopsy documents tumor.\n     * 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 detected ONLY by flow cytometry, RT PCR, FISH, or immunohistochemistry will NOT be considered to have clinical bone marrow involvement for the purposes of this study.\n\n     For participants that have a positive FDG-PET scan at study enrollment, a bilateral bone marrow biopsy will be required at study entry. If a bone marrow is required, the suggested approach for participants with large pelvic tumors in which a posterior iliac crest bone marrow biopsy would track through the tumor is to instead undergo 2 marrow biopsies on the contralateral side (either 2 posterior biopsies or one posterior and one anterior biopsy).\n\n     • 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 or CT (whole body FDG-PET\u002FCT or FDG-PET\u002FMR scan acceptable). Whole body technetium bone scans may be performed at the discretion of the investigator and are not required. For participants without other sites of metastatic disease whose sole metastatic site to qualify for study entry is a single area suspicious for bone metastasis identified by FDG-PET, confirmatory biopsy or anatomic imaging evidence of an associated soft tissue mass at that site is required for study entry.\n\n     Prior Therapy\n  3. Participants must have completed 6 cycles of Induction therapy with VDC\u002FIE per US standard of care (including standard modifications). Participants will enroll after the 6th cycle prior to local control.\n\n     Organ Function Requirements\n  4. Adequate renal function defined as:\n\n     * For participants \\\u003C 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL\u002Fmin\u002F1.73 m2) or via radioisotope GFR of ≥ 70 mL\u002Fmin\u002F1.73 m2. The Bedside Schwartz equation is: \\[(0.413) X (Height in cm)\\] \u002F SCr\n     * For participants ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL\u002Fmin\u002F1.73 m2) or via radioisotope GFR of ≥ 70 mL\u002Fmin\u002F1.73 m2. The Cockcroft and Gault formula is: \\[(140-age) x (Wt in kg) x (0.85 if female)\\] \u002F (72 x SCr)\n     * OR a 24 hour urine Creatinine clearance ≥ 70 mL\u002Fmin\u002F1.73 m2\n  5. Adequate liver function defined as:\n\n     * Total bilirubin ≤1.5 x upper limit of normal (ULN) for age, and\n     * SGPT (ALT \\\u003C3 x upper limit of normal (ULN) for age (except for participants with liver metastasis who may enroll if ALT \\\u003C 5 times ULN for age).\n  6. Adequate cardiac function defined as:\n\n     * Shortening fraction of ≥27% or\n     * Ejection fraction of ≥50%\n  7. Participants must have fully recovered from the hematological and bone marrow suppression effects of prior chemotherapy.\n  8. Participants must have a Lansky Play Scale or Karnofsky Performance Scale score of ≥ 60.\n  9. 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.\n  10. Written informed consent in accordance with institutional and FDA guidelines must be obtained from all participants (or participants' legal representative).\n\nExclusion Criteria:\n\n1. BSA of \\\u003C0.25 m2\n2. Investigational Drugs: Participants who are currently receiving another investigational drug are excluded from participation.\n3. Anti-cancer Agents: Participants who are currently receiving other anticancer agents are not eligible.\n4. Participants with regional node involvement as their only site of disease beyond the primary tumor.\n5. Participants whose primary tumors arise in the intra-dural soft tissue (e.g. brain and spinal cord).\n6. Participants with current CNS disease\n7. 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.\n8. 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.\n\nCohort 3:\n\nInclusion Criteria:\n\n* Age\n\n  1. Participants must be less than 30 years of age at enrollment.\n\n     Diagnosis\n  2. Participants must have histologic diagnosis of osteosarcoma at original diagnosis.\n  3. 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:\n\n     * Surgical resection of all possible sites of suspected pulmonary metastases in order to achieve a complete remission within 4 weeks prior to study enrollment\\*\n     * Pathologic confirmation of metastases from at least one of the resected sites.\n     * 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 last lung surgery. No evidence of pulmonary metastatic disease; participants may have no visible lung nodules greater than 3 mm, and not considered to be disease.\n\n     Note: If surgery related changes such as atelectasis are seen on the post-operative CT scan, participants will remain eligible to enroll as long as the operating surgeon believes that all sites of metastases were resected. Participants with positive microscopic margins will be eligible to enroll.\n\n     Performance Level\n  4. Participants must have a Lansky Play Scale or Karnofsky Performance Scale score of ≥ 60.\n\n     Timing from Prior Therapy\n  5. Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.\n\n     * Myelosuppressive anti-cancer therapy: Must not have been received within 2 weeks of study entry (4 weeks if prior nitrosourea).\n     * Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent.\n     * 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.\n     * 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.\n\n     Organ Function Requirements\n  6. Hematological:\n\n     * Platelet count ≥50,000\u002FμL without transfusion in last 7 days\n     * Hgb ≥8.5 without transfusion in last 7 days\n  7. Adequate renal function defined as:\n\n     * For participants \\\u003C 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL\u002Fmin\u002F1.73 m2) or via radioisotope GFR of ≥ 70 mL\u002Fmin\u002F1.73 m2. The Bedside Schwartz equation is: \\[(0.413) X (Height in cm)\\] \u002F SCr\n     * For participants ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL\u002Fmin\u002F1.73 m2) or via radioisotope GFR of ≥ 70 mL\u002Fmin\u002F1.73 m2. The Cockcroft and Gault formula is: \\[(140-age) x (Wt in kg) x (0.85 if female)\\] \u002F (72 x SCr)\n     * OR a 24 hour urine Creatinine clearance ≥ 70 mL\u002Fmin\u002F1.73 m2\n  8. Adequate liver function defined as:\n\n     * Total bilirubin ≤1.5 x upper limit of normal (ULN) for age.\n     * SGPT (ALT \\\u003C3 x upper limit of normal (ULN) for age.\n  9. Adequate cardiac function defined as:\n\n     * Shortening fraction of ≥27%, or\n     * Ejection fraction of ≥50%.\n  10. Adequate pulmonary function defined as:\n\n      o No evidence of dyspnea at rest, no history of exercise intolerance, and a pulse oximetry \\>94%.\n  11. 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.\n  12. Written informed consent in accordance with institutional and FDA guidelines must be obtained from all participants (or participants' legal representative).\n\nExclusion Criteria:\n\n1. BSA of \\\u003C0.25 m2\n2. Investigational Drugs: Participants who are currently receiving another investigational drug are excluded from participation.\n3. Anti-cancer Agents: Participants who are currently receiving other anticancer agents are not eligible.\n4. Participants with distant bone metastases at original diagnosis or any subsequent relapse (participants with only skip lesions will be eligible).\n5. Participants with concurrent local and pulmonary recurrence at the time of most recent episode of disease recurrence preceding enrollment.\n\n   Note: participants who had local recurrence previously that has been treated and then presented with an isolated pulmonary recurrence and met the surgical resection criteria stated above will be eligible (see IC #3 above).\n6. Participants with primary refractory disease with progression of the primary tumor on initial therapy.\n7. Participants with other sites of extra-pulmonary metastases at the time of any episode of disease recurrence preceding enrollment.\n8. 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.\n9. 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.\n\nCohort 4A\u002FB:\n\nInclusion Criteria:\n\nDiagnosis Both Cohorts\n\n1. 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 secondary malignancies.\n\n   o Note: craniofacial osteosarcoma is NOT permitted.\n2. The primary tumor was resectable after the initial 2 cycles of MAP chemotherapy.\n3. 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 be available to submit to BCC.\n\n   Note: Two-view plain radiographs of the primary tumor site can be performed for participants who have a metallic prosthetic implant instead of CT or MRI if a significant metal artifact would occur by those imaging modalities;\n\n   Cohort A only\n4. Participant must have poor response to induction chemotherapy (those with 10% or more viable tumor remaining after surgery) and localized tumor.\n\n   Cohort B only\n5. Have an initial diagnosis of high-grade metastatic extremity or axial osteosarcoma resectable by the treating team.\n\n   o Note: Metastatic pulmonary disease is defined as 3 or more lesions \\>5 mm or 1 lesion \\>1 cm or biopsy proven pulmonary metastatic disease if not meeting these radiographic criteria;\n6. No definite progression of metastatic disease and no evidence of new metastatic disease.\n7. Following definitive primary surgery, complete removal of all metastases or complete removal planned and deemed feasible.\n\n   Non-Diagnostic Inclusion Criteria, Both Cohorts Age\n8. Participants must be ≥5 years and ≤40 years on date of diagnostic biopsy. Performance Level\n9. 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 eligible.\n\n   Prior Therapy\n10. 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 weeks) of MAP. Participants will enroll after the 3rd cycle of MAP.\n\n    Organ Function Requirements\n11. Participants must have adequate renal function defined:\n\n    * For participants \\\u003C 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL\u002Fmin\u002F1.73 m2) or via radioisotope GFR of ≥ 70 mL\u002Fmin\u002F1.73 m2. The Bedside Schwartz equation is: \\[(0.413) X (Height in cm)\\] \u002F SCr\n    * For participants ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL\u002Fmin\u002F1.73 m2) or via radioisotope GFR of ≥ 70 mL\u002Fmin\u002F1.73 m2. The Cockcroft and Gault formula is: \\[(140-age) x (Wt in kg) x (0.85 if female)\\] \u002F (72 x SCr)\n    * OR a 24 hour urine Creatinine clearance ≥ 70 mL\u002Fmin\u002F1.73 m2\n12. Adequate cardiac function defined as:\n\n    * Shortening fraction of ≥28%, or\n    * Ejection fraction of ≥50%\n13. Adequate liver function defined as:\n\n    * Total bilirubin ≤1.5 x upper limit of normal (ULN) for age\n    * SGPT (ALT \\\u003C3 x upper limit of normal (ULN) for age.\n14. Participants must have fully recovered from the hematological and bone marrow suppression effects of prior chemotherapy.\n15. 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.\n16. Written informed consent in accordance with institutional and FDA guidelines must be obtained from all participants (or participants' legal representative).\n\nExclusion Criteria:\n\n1. BSA of \\\u003C0.25 m2\n2. Investigational Drugs: Participants who are currently receiving another investigational drug are excluded from participation.\n3. Anti-cancer Agents: Participants who are currently receiving other anticancer agents are not eligible.\n4. 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.\n5. 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.","0 Years","50 Years",{"count":59,"type":20},406,[23],"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\u002For maintenance therapy we hope to safely observe improved event-free survival and overall survival. There are 5 cohorts covered under this master protocol.",[63,32,33],"Osteosarcoma","2026-06-10",{"date":66,"type":40},"2026-06-12",{"date":68,"type":40},"2026-06-05",{"date":70,"type":20},"2036-06-01",{"name":72,"class":47},"Milton S. Hershey Medical Center"]