[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"refractory-osteosarcoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:refractory-osteosarcoma":30},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,8,0,[8,52,81,134,170,196,221,248],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":31,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":40,"lastUpdatePostDateStruct":41,"startDateStruct":44,"completionDateStruct":46,"leadSponsor":48,"locationsCount":51},"100609221","phase-1-nkg2dzeta-nk-cell-conditioning-with-c7rgd2car-t-cells-for-patients-with-relapsed-or-refractory-osteosarcoma-or-neuroblastoma-100609221",false,"NCT07211737","NKG2D.Zeta-NK Cell Conditioning With C7R.GD2.CAR-T Cells for Patients With Relapsed or Refractory Osteosarcoma or Neuroblastoma","(INCITE-ON) Phase I Study of i15.NKG2D.Zeta-NK Cell Conditioning in the Tumor Micro-environment in Combination With C7R.GD2.CAR-T for the Treatment of Patients With Relapsed or Refractory Osteosarcoma or Neuroblastoma","PROCUREMENT INCLUSION:\n\n1. Patients with Neuroblastoma that have persistent disease after standard treatment or have relapsed\u002Frefractory disease.\n\n   Or\n\n   Patients with Osteosarcoma that have persistent disease after standard treatment or have relapsed\u002Frefractory disease.\n2. Karnofsky\u002FLansky score of 60% or greater.\n3. Informed consent and assent (as applicable) obtained from parent\u002Fguardian and child.\n4. Greater than 1 year of age.\n\nPROCUREMENT EXCLUSION:\n\n1. History of hypersensitivity to murine protein-containing products.\n2. Known presence of Human Anti-Mouse Antibodies (HAMA).\n3. Active autoimmune disease (requiring immunosuppressive treatment in the past 6 months).\n4. Primary brain tumor or known brain metastases (on evaluation by MIBG and\u002For PET if applicable, CT\u002FMRI\u002FLP not required).\n\nTREATMENT INCLUSION:\n\n1. Patients with Neuroblastoma that have persistent disease after standard treatment or have relapsed\u002Frefractory disease.\n\n   Or\n\n   Patients with Osteosarcoma that have persistent disease after standard treatment or have relapsed\u002Frefractory disease.\n2. Karnofsky\u002FLansky score of 50% or greater\n3. Pulse Ox greater than or equal to 90% on room air\n4. AST less than 5 times upper limit of normal (less than 10 times upper normal if known with metastatic liver disease)\n5. Total bilirubin less than 3 times the upper limit of normal\n6. Serum creatinine less than 3 times upper limit of normal\n7. Available autologous T-cells with greater than or equal to 20% expressing GD2.CAR\n8. Informed consent and assent (as applicable) obtained from parent\u002Fguardian and child.\n9. Greater than 1 year of age.\n10. Recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study.\n\nTREATMENT EXCLUSION:\n\n1. History of hypersensitivity to murine protein containing products (patients who have undergone desensitization and successful re-challenge without hypersensitivity reaction are eligible).\n2. Known presence of Human Anti-Mouse Antibodies (HAMA).\n3. Tumor potentially causing airway obstruction per investigator discretion.\n4. Pregnancy or lactation \u002F will not use birth control methods.\n5. Currently receiving immunosuppressive drugs (patients on low dose corticosteroids are eligible: less than 0.25 mg\u002Fkg\u002Fday of prednisone\u002Fequivalent).\n6. Primary brain tumor or known brain metastases (on evaluation by MIBG and\u002For PET if applicable, CT\u002FMRI\u002FLP not required).","ALL","1 Year","24 Years",{"count":20,"type":21},27,"ESTIMATED","INTERVENTIONAL",[24],"PHASE1","The purpose of this study is to find the largest safe dose of i15.NKG2D.zeta-NK cells in combination with C7R.GD2.CAR-T cells, and additionally to evaluate how long they can be detected in patients' blood and what affect they have on patients' cancer.\n\nPatients eligible for this study have neuroblastoma or osteosarcoma that expresses a substance on the cancer cells called GD2. This cancer has either come back after treatment or did not respond to the standard or other investigational treatments or therapies used to treat it. There is no standard treatment for these types of advanced cancers at this time. This is a gene transfer research study using special immune cells called NK cells and T cells. NK cells and T cells are types of white blood cell that help the body fight infection.\n\nThe body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: NK cells and T cells. T cells are special infection-fighting blood cells that can kill cells infected with viruses and tumor cells. NK cells, another kind of infection-fighting cell, can recognize a wide range of cells in distress, including tumor cells and cells that help protect tumor cells in the cancer environment. Both NK cells and T cells have been used individually to treat patients with cancers. They have shown promise, but have not been strong enough individually to cure most patients.\n\nInvestigators have found from previous research that we can put a new gene into T cells that will make them recognize GD2, a substance found on almost all neuroblastoma and osteosarcoma cells. We can also put a new gene into NK cells that help them fight the tumor environment. Investigators know that T cells and NK cells need substances called cytokines to survive but the cells do not get enough cytokines after infusion into the body; therefore, the investigators have added the genes C7R and IL15 into the T and NK cells, respectively, to give each cell a constant supply of cytokine that helps them to survive longer.\n\nThe C7R.GD2.CAR-T cells and i15.NKG2D.zeta-NK cells are investigational products not approved by the Food and Drug Administration.",[27,28,29,30],"Relapsed Neuroblastoma","Refractory Neuroblastoma","Relapsed Osteosarcoma","Refractory Osteosarcoma",[32,33,34,35,36,37,38],"Gene Therapy","CAR T cells","Neuroblastoma","Osteosarcoma","Immunotherapy","chimeric antigen receptor","NK Cell","NOT_YET_RECRUITING","2026-06-30",{"date":42,"type":43},"2026-07-01","ACTUAL",{"date":45,"type":21},"2026-08",{"date":47,"type":21},"2044-04",{"name":49,"class":50},"Baylor College of Medicine","OTHER",1,{"id":53,"slug":54,"hasResults":11,"nctId":55,"briefTitle":56,"officialTitle":57,"acronym":4,"eligibilityCriteria":58,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":59,"enrollmentInfo":60,"targetDuration":4,"studyType":22,"phases":62,"briefSummary":63,"conditions":64,"keywords":67,"overallStatus":71,"whyStopped":4,"lastUpdateSubmitDate":72,"lastUpdatePostDateStruct":73,"startDateStruct":75,"completionDateStruct":77,"leadSponsor":79,"locationsCount":51},"100604033","phase-1-tegavivint-with-gemcitabine-in-patients-with-relapsed-or-refractory-osteosarcoma-100604033","NCT07144254","Tegavivint With Gemcitabine in Patients With Relapsed or Refractory Osteosarcoma","Study of Tegavivint, a Transducin Beta-like Protein 1 (TBL1) Inhibitor, With Gemcitabine in Patients With Relapsed or Refractory Osteosarcoma","Inclusion Criteria:\n\nDiagnosis:\n\nParticipants must have had histologic verification of osteosarcoma at original diagnosis or relapse.\n\n* All participants with relapsed or refractory osteosarcoma are eligible, provided they received front-line treatment with a regimen that contained at least 3 of the following agents: methotrexate, doxorubicin, cisplatin, and ifosfamide\n\n  -Disease Status:\n* Dose Escalation: Participants must have either measurable or evaluable disease per RECIST.Note: Participants with no evidence of disease on imaging (e.g., following pulmonary metastasectomy) are not eligible during the dose escalation phase.\n* Dose Expansion: Participants with measurable or evaluable disease per RECIST and those with no evidence of disease on imaging following pulmonary metastasectomy are eligible during the dose expansion phase.\n\n  -Performance Level: Participants must have a Lansky (≤ 16 years) or Karnofsky (\\> 16 years) score of ≥ 60, or Eastern Cooperative Oncology Group (ECOG) ≤ 2 Note: Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory to assess the performance score.\n\n  -Prior Therapy: Participants must have fully recovered from the clinically significant acute effects of all prior anti-cancer chemotherapy, immunotherapy, surgery, or radiation therapy before enrollment.\n* Myelosuppressive chemotherapy: ≥ 14 days after the last dose.\n* Hematopoietic growth factors: ≥ 14 days after a long-acting growth factor (e.g., pegfilgrastim) or ≥ 7 days for a short-acting growth factor. For agents with known delayed adverse events, extend recovery period accordingly.\n* Biologic (anti-neoplastic) agent: ≥ 7 days after the last dose. Extend period if adverse events occur beyond 7 days.\n* Cellular therapy: ≥ 21 days since last dose (e.g., modified T cells, gamma-delta T cells, natural killer (NK) cells, dendritic cells) with recovery from associated toxicities.\n* Interleukins, interferons, and cytokines (excluding hematopoietic growth factors): ≥ 21 days since last dose.\n* Antibodies: 7 days or 3 half-lives (whichever is longer), up to 30 days. Toxicity must be resolved to Grade ≤ 1.\n* Radiation therapy (XRT):\n\n  * 14 days after local palliative XRT (small port)\n  * 150 days after radiation to ≥ 50% of pelvis or bone marrow\n  * 6 weeks after substantial bone marrow radiation\n\nPrior use of Nucleoside Analogue (Gemcitabine): Allowed. Investigational agents not otherwise specified: ≥ 30 days since last dose. Surgery: ≥ 2 weeks since last major surgery, including pulmonary metastasectomy (central line placement and core\u002Fsmall open biopsies are excluded)\n\nOrgan Function Requirements:\n\n* Adequate Bone Marrow Function Defined As:\n\n  * Peripheral absolute neutrophil count (ANC) ≥ 750\u002Fmm3 (0.75x109\u002FL)\n  * Platelet count ≥ 75,000\u002Fmm3 (75x109\u002FL)\n* Adequate Renal Function Defined As: Creatinine clearance or radioisotope GFR ≥ 70 ml\u002Fmin\u002F1.73 m2\n* Adequate Liver Function Defined As:\n\n  * Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x the upper limit of normal (ULN) for age\n  * ALT ≤ 5 x the ULN\n* Adequate Pulmonary Function Defined As: No dyspnea at rest, no exercise intolerance, and no oxygen requirement (pulse oximetry \\> 93% on room air).\n* Adequate Cardiac Function Defined As: QTc ≤ 470 ms using Fridericia formula\n\nExclusion Criteria:\n\n* CNS disease: Patients with a history of intraparenchymal CNS disease (osteosarcoma) are not eligible unless they have imaging documenting stability of CNS lesions for ≥ 3 months prior to enrollment\n* Pregnancy or Breast-Feeding\n* Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained\n* Males or females of reproductive potential are not eligible unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method\n* Concomitant Medications:\n\n  * Investigational Drugs: Subjects who are currently receiving another investigational drug are not eligible.\n  * Anti-cancer Agents: Subjects who are currently receiving other anti-cancer agents are not eligible.\n  * CYP3A4\u002F5 Agents: Patients currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days before the 1st dose of tegavivint to the end of the study. See Appendix II for a list of agents.\n  * Bisphosphonates: Patients receiving bisphosphonates within 4 Weeks of study enrollment are not eligible.\n  * Denosumab: Patients who have received denosumab within 180 days prior to study enrollment are not eligible\n* Infection: Subjects who have an active, uncontrolled infection.\n* Subjects who have received prior solid organ or allogeneic stem cell transplantation.\n* Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.\n* Patients with a known metabolic bone disease (ex: hyperparathyroidism, Paget's disease, osteomalacia).\n* Patients with a disorder associated with abnormal bone metabolism.\n* Patients with ≥ 2 grade hypocalcemia that is not corrected with oral calcium supplementation.\n* Patients with vitamin D \\\u003C 20 ng\u002FmL will require supplementation or will otherwise be excluded. Patients must agree to take vitamin D +\u002F- calcium supplements (if necessary) according to institutional or published guidelines. Additional calcium supplementation is not required if adequate dietary intake can be ascertained.\n* Patients who have previously received tegavivint are not eligible.","30 Years",{"count":61,"type":21},24,[24],"The goal of this clinical trial is to define the maximum tolerated dose (MTD) and\u002For Recommended phase 2 dose (RP2D) of Tegavivint in combination with Gemcitabine in patients with relapsed or refractory osteosarcoma (OS).\n\nThe study will also investigate the toxicities of Tegavivint in combination with gemcitabine in patients with relapsed or refractory OS.",[65,66,29,30],"Osteosarcoma Recurrent","Osteosarcoma in Children",[68,69,70,35],"Tegavivint","TBL1 inhibitor","Gemcitabine","RECRUITING","2026-05-30",{"date":74,"type":43},"2026-06-02",{"date":76,"type":43},"2026-01-22",{"date":78,"type":21},"2028-05",{"name":80,"class":50},"Emory University",{"id":82,"slug":83,"hasResults":11,"nctId":84,"briefTitle":85,"officialTitle":86,"acronym":4,"eligibilityCriteria":87,"healthyVolunteers":11,"sex":16,"minAge":88,"maxAge":59,"enrollmentInfo":89,"targetDuration":4,"studyType":22,"phases":91,"briefSummary":93,"conditions":94,"keywords":115,"overallStatus":71,"whyStopped":4,"lastUpdateSubmitDate":124,"lastUpdatePostDateStruct":125,"startDateStruct":127,"completionDateStruct":129,"leadSponsor":131,"locationsCount":133},"100431714","phase-1-study-of-onivyde-with-talazoparib-or-temozolomide-in-children-with-recurrent-solid-tumors-and-ewing-sarcoma-100431714","NCT04901702","Study of Onivyde With Talazoparib or Temozolomide in Children With Recurrent Solid Tumors and Ewing Sarcoma","A Randomized Phase I\u002FII Study of Talazoparib or Temozolomide in Combination With Onivyde in Children With Recurrent Solid Malignancies and Ewing Sarcoma","Inclusion Criteria\n\nPatients must be \\> 12 months and \\\u003C 30 years at the time of enrollment on study.\n\nPhase I\n\n* Patients with refractory or recurrent non-central nervous system (CNS) solid tumors not amenable to curative treatment are eligible. Patients must have had histologic verification of malignancy at original diagnosis or at the time of relapse. Patients eligible for the expansion cohort, A2, will include non-ES patients with refractory or recurrent non-CNS solid tumors with a deleterious alteration in germline or somatic genes involved in HR repair and DSBs signaling, germline or somatic assessed by prior comprehensive sequencing performed in a CLIA-approved (or equivalent) facility.\n\nPhase II\n\n* Patients with refractory or recurrent Ewing sarcoma (during or after completion of first-line therapy). Refractory disease is defined as progression during first line treatment or within 12 weeks of completion of first line treatment. Recurrent disease includes patients who received first line treatment and experienced disease progression at any time point \\>12 weeks from the completion of first line therapy.\n* Patients must have a histologic diagnosis of Ewing sarcoma with EWSR1- FLI1 translocation or other EWS rearrangement at the time of initial diagnosis. Repeat biopsy at the time of disease recurrence is strongly encouraged but it is not required\u002Fmandated for enrollment.\n\nDisease status\n\n* Patients must have either measurable or evaluable disease (see Section 7.0 for definitions). Measurable disease includes soft tissue disease evaluable by cross-sectional imaging (RECIST). Patients with bone disease without a measurable soft tissue component or bone marrow disease only are eligible for the phase 1 and phase 2 study but will not be included in the OR endpoint.\n* Performance level: Karnofsky \\> 50% for patients \\> 16 years of age and Lansky \\> 50% for patients \\\u003C 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n\nPrior therapy\n\nPhase I Patients who have received prior therapy with an irinotecan-based or temozolomide-based regimen are eligible. Patients who have received prior therapy with a PARP inhibitor other than talazoparib are eligible.\n\nPhase II\n\n* Patients should have received first line therapy and developed either refractory or recurrent disease (first relapse).\n* Organ function: Must have adequate organ and bone marrow function as defined by the following parameters:\n* Patients with solid tumors not metastatic to bone marrow:\n* Peripheral absolute neutrophil count (ANC) \\>1,000\u002Fmm3 (1x109\u002FL)\n* Platelet count \\> 75,000\u002Fmm3 (75x109\u002FL) (no transfusion within 7 days of enrollment)\n* Hemoglobin \\> 9 g\u002FdL (with or without support)\n\nIn the phase I study, patients with solid tumors metastatic to bone marrow or with bone marrow hypocellularity defined as \\\u003C30% cellularity in at least one bone marrow site will be eligible for study, but they will not be evaluable for hematologic toxicity. These patients must not be refractory to red cell or platelet transfusions. At least 2 of every cohort of 3 patients (in the phase I study) must be evaluable for hematologic toxicity. If dose limiting hematologic toxicity is observed at any dose level, all subsequent patients enrolled at that dose level must be evaluable for hematologic toxicity.\n\n* Adequate renal function defined as: Creatinine clearance or radioisotope GFR \\> 60ml\u002Fmin\u002F1.73m2 or a serum creatinine maximum based on age\u002Fsex: age 6months to \\\u003C1 year, creatinine 0.4; 1 to \\\u003C 2 years, creatinine 0.6; 2 \\\u003C 6 years, creatinine 0.8; 6 \\\u003C 10 years, creatinine 1; 10 to \\\u003C13 years, creatinine 1.2; 13 to \\\u003C 16 years creatinine 1.5 (males) or 1.4 (females); \\> 16 years, creatinine 1.7 (males) 1.4 (females)\n* Adequate liver function defined as: normal liver function as defined by SGPT (ALT) concentration \\\u003C5x the institutional ULN, a total bilirubin concentration \\\u003C2x the institutional ULN for age, and serum albumin \\> 2g\u002FdL.\n* Adequate pulmonary function defined as no evidence of dyspnea at rest and a pulse oximetry \\> 94% if there is a clinical indication for determination. Pulmonary function tests are not required.\n* Patients must have fully recovered from the acute toxic effects of chemotherapy, immunotherapy, surgery, or radiotherapy prior to entering this study:\n* Myelosuppressive chemotherapy: Patient has not received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (8 weeks if received prior myeloablative therapy).\n* Hematopoietic growth factors: At least 7 days must have elapsed since the completion of therapy with a growth factor. At least 14 days must have elapsed after receiving pegfilgrastim.\n* Biologic (anti-neoplastic agent): At least 7 days must have elapsed since completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur.\n* Monoclonal antibodies: At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody or 28 days have elapsed since last dose of the monoclonal antibody with complete resolution of symptoms related to treatment.\n* Radiotherapy: At least 2 weeks must have elapsed since any irradiation; at least 6 weeks must have elapsed since craniospinal RT, 131I-mIBG therapy or substantial bone marrow irradiation (e.g., \\>50% pelvis irradiation).\n* Female participant who is post-menarchal must have a negative urine or serum pregnancy test and must be willing to have additional serum and urine pregnancy tests during the study.\n* Female or male participant of reproductive potential must agree to use effective contraceptive methods at screening and throughout duration of study treatment.\n\nExclusion Criteria\n\nPregnant or breastfeeding\n\n* Pregnant or breast-feeding women will not be entered on this study. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two methods of birth control: a medically accepted barrier of contraceptive method (e.g., male or female condom) and a second method of birth control during protocol therapy. Two highly effective methods of contraception are required for female patients during treatment and for at least 7 months after completing therapy. Male patients with female partners of reproductive potential and\u002For pregnant partners are advised to use two highly effective methods of contraception during treatment and for at least 4 months after the final dose.\n* Male and female participants must agree not to donate sperm or eggs, respectively, after the first dose of study drug through 105 days and 45 days after the last dose of study drug. Females considered not of childbearing potential include those who are surgically sterile (bilateral salpingectomy, bilateral oophorectomy, or hysterectomy).","12 Months",{"count":90,"type":21},90,[24,92],"PHASE2","The phase I portion of this study is designed for children or adolescents and young adults (AYA) with a diagnosis of a solid tumor that has recurred (come back after treatment) or is refractory (never completely went away). The trial will test 2 combinations of therapy and participants will be randomly assigned to either Arm A or Arm B. The purpose of the phase I study is to determine the highest tolerable doses of the combinations of treatment given in each Arm.\n\nIn Arm A, children and AYAs with recurrent or refractory solid tumors will receive 2 medications called Onivyde and talazoparib. Onivyde works by damaging the DNA of the cancer cell and talazoparib works by blocking the repair of the DNA once the cancer cell is damaged. By damaging the tumor DNA and blocking the repair, the cancer cells may die. In Arm B, children and AYAs with recurrent or refractory solid tumors will receive 2 medications called Onivyde and temozolomide. Both of these medications work by damaging the DNA of the cancer call which may cause the tumor(s) to die.\n\nOnce the highest doses are reached in Arm A and Arm B, then \"expansion Arms\" will open. An expansion arm treats more children and AYAs with recurrent or refractory solid tumors at the highest doses achieved in the phase I study. The goal of the expansion arms is to see if the tumors go away in children and AYAs with recurrent or refractory solid tumors. There will be 3 \"expansion Arms\". In Arm A1, children and AYAs with recurrent or refractory solid tumors (excluding Ewing sarcoma) will receive Onivyde and talazoparib. In Arm A2, children and AYAs with recurrent or refractory solid tumors, whose tumors have a problem with repairing DNA (identified by their doctor), will receive Onivyde and talazoparib. In Arm B1, children and AYAs with recurrent or refractory solid tumors (excluding Ewing sarcoma) will receive Onivyde and temozolomide.\n\nOnce the highest doses of medications used in Arm A and Arm B are determined, then a phase II study will open for children or young adults with Ewing sarcoma that has recurred or is refractory following treatment received after the initial diagnosis. The trial will test the same 2 combinations of therapy in Arm A and Arm B. In the phase II, a participant with Ewing sarcoma will be randomly assigned to receive the treatment given on either Arm A or Arm B.",[95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,28,30,111,112,113,114],"Recurrent Solid Tumor","Recurrent Ewing Sarcoma","Recurrent Hepatoblastoma","Recurrent Malignant Germ Cell Tumor","Recurrent Malignant Solid Neoplasm","Recurrent Neuroblastoma","Recurrent Osteosarcoma","Recurrent Peripheral Primitive Neuroectodermal Tumor","Recurrent Rhabdoid Tumor","Recurrent Rhabdomyosarcoma","Recurrent Soft Tissue Sarcoma","Recurrent Wilms Tumor","Refractory Ewing Sarcoma","Refractory Hepatoblastoma","Refractory Malignant Germ Cell Tumor","Refractory Malignant Solid Neoplasm","Refractory Peripheral Primitive Neuroectodermal Tumor","Refractory Rhabdoid Tumor","Refractory Rhabdomyosarcoma","Refractory Soft Tissue Sarcoma",[116,117,118,119,120,121,122,123],"Pediatric Cancer","Childhood Cancer","Ewing Sarcoma","PARP inhibitor","Solid tumor","Irinotecan","Onivyde","Talazoparib","2026-05-18",{"date":126,"type":43},"2026-05-19",{"date":128,"type":43},"2021-06-09",{"date":130,"type":21},"2026-12-31",{"name":132,"class":50},"St. Jude Children's Research Hospital",10,{"id":135,"slug":136,"hasResults":11,"nctId":137,"briefTitle":138,"officialTitle":139,"acronym":4,"eligibilityCriteria":140,"healthyVolunteers":11,"sex":16,"minAge":88,"maxAge":59,"enrollmentInfo":141,"targetDuration":4,"studyType":22,"phases":143,"briefSummary":144,"conditions":145,"keywords":4,"overallStatus":71,"whyStopped":4,"lastUpdateSubmitDate":159,"lastUpdatePostDateStruct":160,"startDateStruct":162,"completionDateStruct":164,"leadSponsor":166,"locationsCount":169},"100427831","phase-1-tegavivint-for-the-treatment-of-recurrent-or-refractory-solid-tumors-including-lymphomas-and-desmoid-tumors-100427831","NCT04851119","Tegavivint for the Treatment of Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors","A Phase 1\u002F2 Study of Tegavivint (NSC#826393) in Children, Adolescents, and Young Adults With Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors","Inclusion Criteria:\n\n* PART A: Patients must be \\>= 12 months and =\\\u003C 21 years of age at the time of study enrollment\n* PART B: Patients must be \\>= 12 months and =\\\u003C 30 years of age at the time of study enrollment\n* Patients with recurrent or refractory solid tumors including non-Hodgkin lymphoma and desmoid tumors are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse\n* PART A: Patients with relapsed or refractory solid tumors, including patients with non-Hodgkin lymphoma and desmoid tumors\n* PART B: Patients with recurrent or refractory Ewing sarcoma, desmoid tumors, osteosarcoma, liver tumors (HCC and hepatoblastoma), Wilms tumor, and tumors with Wnt pathway aberrations. For the Wnt pathway aberrations cohort we will include the most common CTNNB1 mutations (S37F, S45F, T41A, S45P, S33C, S37C, D32Y, S33F, T41I, G34R, G34V, D32N, S33P, G34E, D32G) as well as any loss of function mutations in the APC, Axin2FBXW7, TCF7L2, and RNF43 genes or any gain-of-function mutations in the GSK3B, LRP6, and LGR5 genes. For patients without prior sequencing, immunohistochemistry (IHC), is required. IHC showing strong nuclear beta-catenin staining will be accepted for the following tumor types: colorectal carcinoma, melanoma, endometrial cancer, ovarian cancer, neuroblastoma, non-Hodgkin lymphoma, pancreatic ductal adenocarcinoma, and solid pseudopapillary tumor of the pancreas\n* PART A: Patients must have either measurable or evaluable disease. For desmoid tumors, the patient must have disease that the investigator deems unresectable or sufficiently morbid or potentially life-threatening that there is favorable risk\u002Fbenefit to the patient to participate in the trial\n* PART B: Patients must have measurable disease. For desmoid tumors, the patient must have measurable disease that the investigator deems unresectable or sufficiently morbid or potentially life-threatening that there is favorable risk\u002Fbenefit to the patient to participate in the trial\n* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \\> 16 years of age and Lansky for patients =\\\u003C 16 years of age\n* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately.\n\n  * Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive\n\n    * Solid tumor patients: \\>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)\n    * Non-Hodgkin lymphoma patients\n\n      * A waiting period prior to enrollment is not required for patients receiving standard maintenance chemotherapy (i.e., corticosteroid, vincristine, thioguanine \\[6MP\\], and\u002For methotrexate)\n      * \\>= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy\n      * NOTE: Cytoreduction with hydroxyurea must be discontinued \\>= 24 hours prior to the start of protocol therapy\n  * Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil counts \\[ANC\\]): \\>= 7 days after the last dose of agent\n  * Antibodies: \\>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\\\u003C 1\n  * Corticosteroids: If used to modify immune adverse events related to prior therapy, \\>= 14 days must have elapsed since last dose of corticosteroid\n  * Hematopoietic growth factors: \\>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur\n  * Interleukins, interferons and cytokines (other than hematopoietic growth factors): \\>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)\n  * Stem cell Infusions (with or without total-body irradiation \\[TBI\\]):\n\n    * Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \\>= 84 days after infusion and no evidence of graft versus host disease (GVHD)\n    * Autologous stem cell infusion including boost infusion: \\>= 42 days.\n  * Cellular therapy: \\>= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \\[NK\\] cells, dendritic cells, etc.).\n  * External beam radiation therapy (XRT)\u002Fexternal beam irradiation including protons: \\>= 14 days after local XRT; \\>= 150 days after TBI, craniospinal XRT or if radiation to \\>= 50% of the pelvis; \\>= 42 days if other substantial bone marrow (BM) radiation\n  * Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 \\[131I MIBG\\]): \\>= 42 days after systemically administered radiopharmaceutical therapy\n  * Patients must not have received prior exposure to tegavivint\n* PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Peripheral absolute neutrophil count (ANC) \\>= 1000\u002FuL (within 7 days prior to enrollment)\n* PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Platelet count \\>= 100,000\u002FuL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 7 days prior to enrollment)\n* PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Hemoglobin \\>= 8.0 g\u002FdL at baseline (may receive red blood cell \\[RBC\\] transfusions) (within 7 days prior to enrollment)\n* Patients with known bone marrow metastatic disease will be eligible for study provided they meet blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled on Part A must be evaluable for hematologic toxicity\n* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \\>= 70 mL\u002Fmin\u002F1.73 m\\^2 or a creatinine based on age\u002Fgender as follows (within 7 days prior to enrollment):\n\n  * Age; maximum serum creatinine\n  * Age 1 to \\\u003C 2 years; 0.6 mg\u002FdL (male); 0.6 mg\u002FdL (female)\n  * Age 2 to \\\u003C 6 years; 0.8 mg\u002FdL (male); 0.8 mg\u002FdL (female)\n  * Age 6 to \\\u003C 10 years; 1 mg\u002FdL (male); 1 mg\u002FdL (female)\n  * Age 10 to \\\u003C 13 years; 1.2 mg\u002FdL (male); 1.2 mg\u002FdL (female)\n  * Age 13 to \\\u003C 16 years; 1.5 mg\u002FdL (male); 1.4 mg\u002FdL (female)\n  * Age \\>= 16 years; 1.7 mg\u002FdL (male); 1.4 mg\u002FdL (female)\n* PATIENTS WITH SOLID TUMORS: Bilirubin (sum of conjugated + unconjugated or total) =\\\u003C 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)\n* PATIENTS WITH SOLID TUMORS: Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \\[ALT\\]) =\\\u003C 135 U\u002FL. For the purpose of this study, the ULN for SGPT is 45 U\u002FL (within 7 days prior to enrollment)\n* PATIENTS WITH SOLID TUMORS: Albumin \\>= 2 g\u002FdL (within 7 days prior to enrollment)\n\nExclusion Criteria:\n\n* Pregnant or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control\n* Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, \\>= 14 days must have elapsed since last dose of corticosteroid\n* Patients who are currently receiving another investigational drug are not eligible\n* Patients who are currently receiving other anti-cancer agents are not eligible\n* Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial\n* Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to the 1st dose of tegavivint to the end of the study\n* Patients who have received bisphosphonates within 4 weeks prior to study enrollment will be excluded\n* Patients who have received denosumab within 180 days prior to study enrollment will be excluded\n* Patients with primary brain tumors are ineligible\n* Patients with known central nervous system (CNS) metastasis, except for craniopharyngeal tumors, will be excluded\n* Patients with a known metabolic bone disease (ex: hyperparathyroidism, Paget's disease, osteomalacia) are not eligible\n* Patients with a disorder associated with abnormal bone metabolism will be excluded\n* Patients with grade \\>= 2 hypocalcemia that is not corrected with oral calcium supplementation will be excluded\n* Patients with vitamin D \\\u003C 20 ng\u002FmL will require supplementation, or will otherwise be excluded. Patients must agree to take vitamin D +\u002F- calcium supplements (if necessary) according to institutional or published guidelines. Additional calcium supplementation is not required if adequate dietary intake can be ascertained\n* Patients with pre-existing grade 3 osteoporosis are excluded\n* Patients who have an uncontrolled infection are not eligible\n* Patients who have received a prior solid organ transplantation are not eligible\n* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible",{"count":142,"type":21},147,[24,92],"This phase I\u002FII trial evaluates the highest safe dose, side effects, and possible benefits of tegavivint in treating patients with solid tumors that has come back (recurrent) or does not respond to treatment (refractory). Tegavivint interferes with the binding of beta-catenin to TBL1, which may help stop the growth of tumor cells by blocking the signals passed from one molecule to another inside a cell that tell a cell to grow.",[146,147,148,34,149,150,151,96,97,152,99,153,101,154,107,108,155,110,156,30,157,158],"Colorectal Carcinoma","Endometrial Carcinoma","Melanoma","Ovarian Carcinoma","Pancreatic Ductal Adenocarcinoma","Recurrent Desmoid Fibromatosis","Recurrent Hepatocellular Carcinoma","Recurrent Non-Hodgkin Lymphoma","Refractory Desmoid Fibromatosis","Refractory Hepatocellular Carcinoma","Refractory Non-Hodgkin Lymphoma","Solid Pseudopapillary Neoplasm of the Pancreas","Wilms Tumor","2026-05-01",{"date":161,"type":43},"2026-05-05",{"date":163,"type":43},"2021-11-08",{"date":165,"type":21},"2028-06-30",{"name":167,"class":168},"Children's Oncology Group","NETWORK",21,{"id":171,"slug":172,"hasResults":11,"nctId":173,"briefTitle":174,"officialTitle":175,"acronym":4,"eligibilityCriteria":176,"healthyVolunteers":11,"sex":16,"minAge":177,"maxAge":4,"enrollmentInfo":178,"targetDuration":4,"studyType":22,"phases":180,"briefSummary":181,"conditions":182,"keywords":4,"overallStatus":71,"whyStopped":4,"lastUpdateSubmitDate":186,"lastUpdatePostDateStruct":187,"startDateStruct":189,"completionDateStruct":191,"leadSponsor":193,"locationsCount":195},"100440776","phase-2-atezolizumab-and-cabozantinib-for-the-treatment-of-adolescents-and-young-adults-with-recurrent-or-metastatic-osteosarcoma-tacos-study-100440776","NCT05019703","Atezolizumab and Cabozantinib for the Treatment of Adolescents and Young Adults With Recurrent or Metastatic Osteosarcoma, TACOS Study","A Phase 2 Trial of Atezolizumab and Cabozantinib in Adolescents and Young Adults With Recurrent\u002FMetastatic Osteosarcoma (TACOS)","Inclusion Criteria:\n\n* Signed informed consent form\n* Age \\>= 12 years at time of signing informed consent form\n* Ability to comply with the study protocol, in the investigator's judgment\n* Histologically confirmed diagnosis of osteosarcoma\n* Metastatic or unresectable locally advanced disease\n* Patients must have relapsed or become refractory to conventional therapy including some combination of cisplatin, doxorubicin, methotrexate, and\u002For ifosfamide\n* Measurable disease per RECIST version (v)1.1 (Note: Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation)\n* Availability of a representative tumor specimen for exploratory biomarker research. Archival samples are permitted if the tumor samples been obtained within 6 months prior to enrollment and the patient has not received intervening therapy\n\n  * A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 15 slides containing unstained, freshly cut, serial sections should be submitted along with an associated pathology report prior to study enrollment. If only 10-14 slides are available, the patient may still be eligible for the study, after principal investigator confirmation has been obtained\n  * If archival tumor tissue is unavailable or is determined to be unsuitable for required testing, tumor tissue must be obtained from a biopsy performed at screening\n* Eastern Cooperative Oncology Group (ECOG) of 0, 1 or 2. Use Karnofsky \\>= 50 for patients \\> 16 years of age and Lansky \\>= 50 for patients =\\\u003C 16 years of age\n* Body surface area (BSA) \\>= 1 m\\^2\n* Life expectancy \\>= 6 months\n* Recovery to baseline or =\\\u003C grade 1 CTCAE v5 from toxicities related to any prior treatments, unless adverse events (AE\\[s\\]) are clinically nonsignificant and\u002For stable on supportive therapy\n* Absolute neutrophil count (ANC) \\>= 1.0 x 10\\^9\u002FL (1000\u002FuL) without granulocyte colony-stimulating factor support (obtained within 14 days prior to initiation of study treatment)\n* Lymphocyte count \\>= 0.5 x 10\\^9\u002FL (500\u002FuL) (obtained within 14 days prior to initiation of study treatment)\n* Platelet count \\>= 100 x 10\\^9\u002FL (100,000\u002FuL) without transfusion (obtained within 14 days prior to initiation of study treatment)\n* Hemoglobin \\>= 90 g\u002FL (9 g\u002FdL) (obtained within 14 days prior to initiation of study treatment)\n\n  * Patients may be transfused to meet this criterion\n* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =\\\u003C 3 x upper limit of normal (ULN) for age (obtained within 14 days prior to initiation of study treatment)\n* Alkaline phosphatase (ALP) =\\\u003C 3 x upper limit of normal (ULN) for age, with the following exceptions: patients with documented bone metastases: ALP =\\\u003C 5 x ULN (obtained within 14 days prior to initiation of study treatment)\n* Serum bilirubin =\\\u003C 1.5 x ULN with the following exception: patients with known Gilbert disease: serum bilirubin =\\\u003C 3 x ULN (obtained within 14 days prior to initiation of study treatment)\n* Creatinine clearance \\>= 50 mL\u002Fmin (adults \\> 18 years of age, calculated using the Cockcroft-Gault formula) or \\>= 50 mL\u002Fmin\u002F1.73m\\^2 (pediatrics patients age 12 - 17, calculated using the Bedside Schwartz equation) (obtained within 14 days prior to initiation of study treatment)\n* Urine protein\u002Fcreatinine ratio (UPCR) =\\\u003C 1 mg\u002Fmg (=\\\u003C 113.2 mg\u002Fmmol), or 24-hour (h) urine protein =\\\u003C 1 g (obtained within 14 days prior to initiation of study treatment)\n* Serum albumin \\>= 20 g\u002FL (2.0 g\u002FdL) (obtained within 14 days prior to initiation of study treatment)\n* For patients not receiving therapeutic anticoagulation: international normalized ratio (INR) or activated partial thromboplastin (aPTT) =\\\u003C 1.5 x ULN (obtained within 14 days prior to initiation of study treatment)\n* Negative human immunodeficiency virus (HIV) test at screening\n* Negative hepatitis B surface antigen (HBsAg) test at screening\n* Women of childbearing potential must not be pregnant at screening. A woman is considered to be of childbearing potential if she is postmenarchal, unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \\> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \\\u003C 55 years-of-age must have a serum follicle stimulating \\[FSH\\] level \\> 40 mIU\u002FmL to confirm menopause). Note: documentation may include review of medical records, medical examinations, or medical history interview by study site\n* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods as defined below:\n\n  * Women must remain abstinent or use contraceptive methods with a failure rate of \\\u003C 1% per year during the treatment period and for 5 months after the final dose of study treatment with either atezolizumab or cabozantinib\n  * Examples of contraceptive methods with a failure rate of \\\u003C 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices\n  * Hormonal contraceptive methods must be supplemented by a barrier method (including male condom, female condom, or diaphragm with spermicidal gel)\n  * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception\n* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:\n\n  * With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 5 months after the final dose of cabozantinib to avoid exposing the embryo. Men must refrain from donating sperm during this same period\n  * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing drug exposure\n\nExclusion Criteria:\n\n* Inability to swallow tablets\n* Prior treatment with cabozantinib\n* Prior treatment with immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies if given in combination with a VEGF-targeted tyrosine kinase inhibitor (TKI). Patients receiving prior anti-PD-1, anti-PD-L1, with or without anti-CTLA-4 antibodies will not be excluded\n* Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment\n* Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment\n* Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Patients with clinically relevant ongoing complications from prior radiation therapy are not eligible\n* 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 after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Patients must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible patients must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment\n* History of leptomeningeal disease\n* Uncontrolled tumor-related pain\n\n  * Patients requiring pain medication must be on a stable regimen at study entry\n  * Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation\n  * Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment\n* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)\n\n  * Patients with indwelling catheters (e.g., PleurX) are allowed\n* Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:\n\n  * Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH)\n  * Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in patients without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor\n* Uncontrolled or symptomatic hypercalcemia (ionized calcium \\> 1.5 mmol\u002FL, calcium \\> 12 mg\u002FdL or corrected serum calcium \\> upper limit of normal \\[ULN\\])\n* Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:\n\n  * Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.\n  * Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.\n  * Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:\n\n    * Rash must cover 10% of body surface area\n    * Disease is well controlled at baseline and requires only low-potency topical corticosteroids\n    * No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months\n* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan\n\n  * History of radiation pneumonitis in the radiation field (fibrosis) is permitted\n* Active tuberculosis\n* Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina\n* Uncontrolled hypertension defined as sustained blood pressure (BP) \\> 140 mm Hg systolic or \\> 90 mm Hg diastolic (patients \\> 13 years of age) or stage 2 hypertension (HTN) as defined by the American Academy of Pediatrics (AAP) as systolic and diastolic BP \\>= 95th percentile+12 mmHg, or \\>= 140\u002F90 mmHg (whichever is lower, patients \\\u003C 13 years of age) despite optimal antihypertensive treatment\n* Stroke (including transient ischemic attack \\[TIA\\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment\n\n  * Patients with a diagnosis of incidental, subsegmental pulmonary embolism (PE) or deep vein thrombosis (DVT) within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion) for at least 1 week before first dose of study treatment\n* Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation\n\n  * The patient has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction\n  * Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment\n  * Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment\n* Moderate to severe hepatic impairment (Child-Pugh B or C)\n* Uncompensated\u002Fsymptomatic hypothyroidism\n* 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 12 weeks before first dose of study treatment\n* Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation\n* Lesions invading or encasing any major blood vessels\n* Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study. Minor surgeries within 10 days before first dose of study treatment. Patients must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Patients with clinically relevant ongoing complications from prior surgery are not eligible\n* Corrected QT interval calculated by the Fridericia formula (QTcF) \\> 500 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment\n\n  * Note: If a single ECG shows a QTcF with an absolute value \\> 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility\n* History of malign","12 Years",{"count":179,"type":21},40,[92],"This phase II trial studies the effect of atezolizumab and cabozantinib in treating adolescents and young adults with osteosarcoma that has come back (recurrent) or has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab and cabozantinib may help to control the osteosarcoma.",[183,184,101,30,185],"Locally Advanced Osteosarcoma","Metastatic Osteosarcoma","Unresectable Osteosarcoma","2026-04-15",{"date":188,"type":43},"2026-04-17",{"date":190,"type":43},"2023-04-25",{"date":192,"type":21},"2027-12-31",{"name":194,"class":50},"M.D. Anderson Cancer Center",2,{"id":197,"slug":198,"hasResults":11,"nctId":199,"briefTitle":200,"officialTitle":201,"acronym":4,"eligibilityCriteria":202,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":203,"enrollmentInfo":204,"targetDuration":4,"studyType":22,"phases":206,"briefSummary":207,"conditions":208,"keywords":210,"overallStatus":71,"whyStopped":4,"lastUpdateSubmitDate":212,"lastUpdatePostDateStruct":213,"startDateStruct":215,"completionDateStruct":217,"leadSponsor":219,"locationsCount":51},"100610437","phase-1-genetically-engineered-cells-fh-folr1-st-car-t-cells-for-the-treatment-of-advanced-refractory-or-recurrentprogressive-osteosarcoma-fierce-trial-100610437","NCT07227571","Genetically Engineered Cells (FH-FOLR1 ST CAR T Cells) for the Treatment of Advanced Refractory or Recurrent\u002FProgressive Osteosarcoma, FIERCe Trial","FIERCe: FOLR1 Immune Effector Cell Therapy Against Advanced Osteosarcoma","Inclusion Criteria:\n\n* Age 1-75 years at the time of enrollment\n* Tissue confirmation of osteosarcoma diagnosis\n* Must have received an anthracycline-based regimen or been deemed ineligible to receive this therapy\n* Must have at least one of the following in the 6 months prior to trial consent:\n\n  * New site of measurable disease by radiographic imaging or histologic confirmation\n  * New site of evaluable disease by radiographic imaging or histologic confirmation\n  * Greater than 20% increase in at least one tumor dimension documented by CT\u002FMRI, AND a minimum absolute increase of 5 mm in longest dimension of existing lesion(s) (previously irradiated lesions may be included)\n  * Persistent measurable disease or fludeoxyglucose F-18 (FDG)-PET avid bone metastasis that has failed to achieve complete remission to upfront conventional therapy (surgery, radiotherapy, and\u002For chemotherapy)\n* All anti-cancer therapy must be discontinued at enrollment\u002Ftime of apheresis, with the following washout periods observed:\n\n  * Chemotherapy and biologic agents: ≥ 7 days prior to enrollment\n  * Steroid use: All corticosteroid therapy (unless physiologic replacement dosing and\u002For topical administration (e.g., inhaled or dermatologic) ≥ 7 days prior to enrollment\n  * Tyrosine kinase inhibitor (TKI) use: ≥ 7 days prior to enrollment\n  * Antitumor antibody therapy (including immune checkpoint inhibitor) must be ≥ 3 half-lives or 30 days, whichever is shorter, from time of enrollment\n  * FOLR1 targeting therapy must be discontinued at least 30 days prior to enrollment\n  * Gene modified cellular therapy: At enrollment, must be at least 30 days from most recent gene modified cell therapy infusion and document no evidence of modified cells in the peripheral blood OR must be at least 60 days from most recent gene modified cell therapy\n  * Washout periods not applicable to patients with apheresis product or usable T cell product available for use at time of enrollment\n* Potential trial participants should have recovered to grade 1 from clinically significant adverse events of their most recent therapy\u002Fintervention prior to enrollment\n* Ability to understand and willingness to sign a written informed consent document.\n* Females of child-bearing potential and fertile male participants must be willing to use an effective contraceptive method before, during, and for at least 12 months after the FOLR1 CART cell infusion\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (if treated at adult facility) or Lansky\u002FKarnofsky score ≥ 60 (if treated at pediatric facility). Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for purposes of assessing performance status\n* Life expectancy ≥ 8 weeks\n* Able to tolerate apheresis, including placement of temporary apheresis catheter, if necessary, or already has an apheresis product available for use in manufacturing\n* Participants 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 are eligible for this trial\n* Participants with treated brain metastases are eligible if they meet the following criteria:\n\n  * Follow-up brain imaging taken at screening demonstrates no evidence of progression and that imaging occurs 3 months after central nervous system (CNS)-directed therapy has been completed\n  * No ongoing, symptomatic CNS pathology requiring medical intervention\n* Serum creatinine ≤ 1.5 x upper limit of normal (ULN) based on age and gender; or estimated creatinine clearance \\> 50 mL\u002Fmin as calculated using the Cockcroft-Gault formula and not dialysis dependent\n\n  * Age: 1 to \\\u003C 2 years; maximum serum creatinine (mg\u002FdL): 0.6 (male), 0.6 (female)\n  * Age: 2 to \\\u003C 6 years; maximum serum creatinine (mg\u002FdL): 0.8 (male), 0.8 (female)\n  * Age: 6 to \\\u003C 10 years; maximum serum creatinine (mg\u002FdL): 1 (male), 1 (female)\n  * Age: 10 to \\\u003C 13 years; maximum serum creatinine (mg\u002FdL): 1.2 (male), 1.2 (female)\n  * Age: 13 to \\\u003C 16 years; maximum serum creatinine (mg\u002FdL): 1.5 (male), 1.4 (female)\n  * Age: ≥ 16 years; maximum serum creatinine (mg\u002FdL): 1.7 (male), 1.4 (female)\n* Total bilirubin ≤ 3 x ULN or conjugated bilirubin ≤ 2 mg\u002FdL. Participants with suspected Gilbert syndrome may be included if total bilirubin (Bili) \\> 3 mg\u002FdL but no other evidence of hepatic dysfunction\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \\\u003C 5 x ULN\n* Pulmonary: ≤ grade 1 dyspnea at rest and arterial oxygen saturation (SaO2) ≥ 92% on ambient air. If pulmonary function tests (PFTs) are performed based on the clinical judgement of the treating physician, participants with forced expiratory volume in 1 second (FEVI) ≥ 50% of predicted and diffusion capacity of the lung for carbon monoxide (DLCO) (corrected) of ≥ 40% of predicted will be eligible\n* Left ventricular ejection fraction (LVEF) may be established with echocardiogram or MUGA scan, and left ejection fraction must be ≥ 50% or shortening fraction ≥ 28%\n* Absolute neutrophil count (ANC) ≥ 500 cells\u002F mm\\^3\n* Hemoglobin ≥ 8 g\u002FdL\n* Platelets ≥ 100,000 per mm\\^3\n* Participants receiving blood product transfusion are acceptable as long as they are not determined to be transfusion refractory\n\nExclusion Criteria:\n\n* Active autoimmune disease: Participants with active autoimmune disease requiring immunosuppressive therapy are excluded. Case by case exemptions are possible with approval by PI\n* Corticosteroid therapy at a dose equivalent of \\> 15 mg of prednisone per day (or equivalent). Pulsed corticosteroid use for disease control is acceptable. For participants weighing ≤ 30 kg, systemic steroids ≥ 0.5 mg prednisone equivalent\u002Fkg\u002Fday\n* Concurrent use of other investigational anti-cancer agents\n* Active uncontrolled infection: HIV positive participants on highly active antiretroviral therapy (HAART) with a CD4 count \\> 500 cells\u002Fmm\\^3 are considered controlled, as are individuals with a history of hepatitis C who have successfully completed antiviral therapy with an undetectable viral load, and those with hepatitis B who have hepatitis well controlled on medication\n* Uncontrolled concurrent illness: Participants may not have uncontrolled or concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia that would limit compliance with study requirements\n* Active treatment for prior immune related adverse event to any immunotherapy: Participants receiving ongoing treatment for prior serious immune-related adverse events are excluded, with exception of hormone supplementation or corticosteroid therapy at equivalent of \\> 15 mg prednisone (or equivalent) per day, unless otherwise approved by PI\n* Significant underlying neurologic disease: Study participants must not have significant active underlying neurologic disease, unless approved by PI. Peripheral neuropathy related to diabetes or prior chemotherapy is acceptable\n* Pregnant, possibly pregnant or those expecting to conceive or father children for the duration of the trial through 4 months after T cell infusion\n* Participants unwilling to provide consent\u002Fassent for participation in the study and 15-year follow-up period if CAR T cell therapy is administered\n* Other medical, social, or psychiatric factor that interferes with medical appropriateness and\u002For ability to comply with study, as determined by the PI\n* Known allergic reactions to any of the components of study treatments","75 Years",{"count":205,"type":21},30,[24],"This phase I trial tests the safety, side effects, and best dose of FH-FOLR1 ST chimeric antigen receptor (CAR) T cells and how well they work in treating patients with osteosarcoma that recurred or spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and that has not responded to previous treatment (refractory) or has come back after a period of improvement (recurrent)\u002Fis growing, spreading, or getting worse (progressive). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they attack tumor cells. T cells are taken from a patient's blood through a process called apheresis. Then the gene for a special receptor that binds to a certain protein on the patient's tumor cells, such as FOLR1, is added to the T cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by an intravenous infusion. Chemotherapy drugs, such as fludarabine and cyclophosphamide, are given to a patient before the manufactured FH-FOLR1 ST CAR T cells to make room for the CAR T cells in the blood and to enhance the CAR T cell activity in the patient. FH-FOLR1 ST CAR T cells may be safe, tolerable, and\u002For effective in treating patients with advanced refractory or recurrent\u002Fprogressive osteosarcoma.",[209,101,30],"Advanced Osteosarcoma",[211],"Bones and Joints","2026-02-09",{"date":214,"type":43},"2026-02-11",{"date":216,"type":43},"2026-01-16",{"date":218,"type":21},"2044-01-31",{"name":220,"class":50},"Fred Hutchinson Cancer Center",{"id":222,"slug":223,"hasResults":11,"nctId":224,"briefTitle":225,"officialTitle":226,"acronym":227,"eligibilityCriteria":228,"healthyVolunteers":11,"sex":16,"minAge":88,"maxAge":4,"enrollmentInfo":229,"targetDuration":4,"studyType":22,"phases":230,"briefSummary":231,"conditions":232,"keywords":233,"overallStatus":71,"whyStopped":4,"lastUpdateSubmitDate":240,"lastUpdatePostDateStruct":241,"startDateStruct":243,"completionDateStruct":245,"leadSponsor":247,"locationsCount":51},"100470036","phase-1-allogeneic-expanded-gamma-delta-t-cells-with-gd2-chemoimmunotherapy-in-relapsed-refractory-neuroblastoma-or-refractory-relapsed-osteosarcoma-100470036","NCT05400603","Allogeneic Expanded Gamma Delta T Cells With GD2 Chemoimmunotherapy in Relapsed \u002FRefractory Neuroblastoma or Refractory\u002F Relapsed Osteosarcoma","A Phase I Study of Allogeneic Ex Vivo Expanded Gamma Delta (γδ) T Cells in Combination With Dinutuximab, Temozolomide, Irinotecan, and Zoledronate in Children With Refractory\u002F Relapsed, or Progressive Neuroblastoma or Refractory\u002F Relapsed Osteosarcoma","Aflac-NBL-2002","Inclusion Criteria:\n\n* Patients must be ≥ 12 months of age at the time of enrollment in the study.\n* Diagnosis: Histological confirmation of neuroblastoma or ganglioneuroblastoma at initial diagnosis. (Bone marrow samples with positive catecholamines are acceptable as confirmation of neuroblastoma) OR histological confirmation of osteosarcoma at diagnosis\n* Response to prior therapy:\n\n  * High-risk neuroblastoma with refractory, relapsed or progressive disease, defined as:\n  * First or greater relapse of neuroblastoma following completion of aggressive multi- drug frontline therapy.\n  * First episode of progressive neuroblastoma during aggressive multi-drug frontline therapy.\n  * Persistent\u002Frefractory neuroblastoma as defined by less than a complete response by the revised International Neuroblastoma Response Criteria (INRC) after at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (such as A3973 or ANBL0532).\n  * Note that this excludes patients initially considered low or intermediate-risk neuroblastoma that progressed to high-risk disease but the patient has not progressed after the diagnosis of high-risk neuroblastoma.\n  * Relapsed or refractory osteosarcoma that is not responsive to standard treatment\n* Disease Status\n\n  * Patients must have measurable or evaluable disease per revised INRC for subjects with neuroblastoma or measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for subjects with Osteosarcoma\n  * Performance Level:Patients must have a Lansky (≤16 years) or Karnofsky (\\>16 years) score of ≥50\n* Prior Therapy\n\n  * Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy before study registration.\n\n    * Prior dinutuximab therapy is allowed regardless of prior response or progression on dinutuximab\n    * Prior temozolomide therapy is allowed\n    * Prior zoledronate is allowed\n    * Prior dinutuximab\u002Ftemozolomide\u002Firinotecan chemoimmunotherapy is allowed\n    * Prior T cell therapy is excluded\n* Organ Function Requirements:\n\n  * Hematologic Functions : Absolute Neutrofil count ≥750\u002FuL and platelet count ≥ 75,000\u002Fµl, transfusion independent .\n  * Renal Function: Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN for age.\n  * Liver Function: Total bilirubin ≤ 1.5 x ULN for age and serum glutamic-pyruvic transaminase (SGPT) (ALT) ≤ 135 U\u002FL (≤ 3x ULN).\n  * Cardiac Function: Normal ejection fraction (≥ 55%) documented by either echocardiogram or radionuclide multigated acquisition scan (MUGA) evaluation OR Normal fractional shortening (≥ 27%) documented by echocardiogram\n  * Pulmonary Function: Normal pulmonary function with no evidence of dyspnea at rest, no exercise intolerance.\n\nExclusion Criteria:\n\n* Prior T cell therapy\n* Pregnancy, breast feeding, or unwillingness to use effective contraception during the study will not be entered on this study.\n* Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.\n* Patients with known active Central Nervous System (CNS) disease (excluding skull disease with intracranial extension). Patients with a history of CNS disease are required to have a brain CT and\u002F or MRI at study registration.\n* Patients with prior allogeneic stem cell transplant\n* Patients who are on hemodialysis\n* Patients with an active or uncontrolled infection. Patients on prolonged antifungal therapy are still eligible if they are culture negative, afebrile, and meet other organ function criteria\n* Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C. Testing is not required in the absence of clinical findings or suspicion.\n* Patients with disease of any major organ system that would compromise their ability to withstand therapy.\n* Patients who have had to permanently discontinue Dinutuximab due to toxicity\n* Patients with serious, uncontrolled cardiac arrhythmias\n* Patients with a history of myocarditis\n* Patients who have received any live vaccines within 30 days before enrollment",{"count":61,"type":21},[24],"The goal of this clinical trial is to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of allogeneic expanded γδ T cells when delivered with Dinutuximab, temozolomide, irinotecan, and zoledronate in children with refractory or recurrent neuroblastoma or refractory\u002F relapsed osteosarcoma as well as to define the toxicities of allogeneic expanded γδ T cells when delivered with Dinutuximab, temozolomide, irinotecan, and zoledronate",[34,28,27,29,30],[234,235,236,237,121,238,239],"Gamma Delta T Cells","Dinutuximab","Temozolomide","Zoledronate","GD2","chemoimmunotherapy","2025-12-19",{"date":242,"type":43},"2025-12-26",{"date":244,"type":43},"2023-11-06",{"date":246,"type":21},"2026-12",{"name":80,"class":50},{"id":249,"slug":250,"hasResults":11,"nctId":251,"briefTitle":252,"officialTitle":253,"acronym":4,"eligibilityCriteria":254,"healthyVolunteers":11,"sex":16,"minAge":255,"maxAge":4,"enrollmentInfo":256,"targetDuration":4,"studyType":22,"phases":258,"briefSummary":259,"conditions":260,"keywords":261,"overallStatus":39,"whyStopped":4,"lastUpdateSubmitDate":264,"lastUpdatePostDateStruct":265,"startDateStruct":267,"completionDateStruct":269,"leadSponsor":271,"locationsCount":51},"100547783","phase-1-im83-clinical-study-of-car-t-cell-therapy-in-patients-with-relapsed-or-refractory-osteosarcoma-100547783","NCT06412458","IM83 Clinical Study of CAR-T Cell Therapy in Patients With Relapsed or Refractory Osteosarcoma","Phase I Clinical Study to Evaluate the Safety and Efficacy of IM83 CAR-T Cells for the Treatment of Relapsed or Refractory Osteosarcoma","Inclusion Criteria:\n\n1. Age ≥ 16 years, both male and female;\n2. Subjects with a diagnosis of osteosarcoma of the extremity confirmed by pathohistologic examination;\n3. To enroll subjects with recurrent or refractory extremity osteosarcoma who have failed or are intolerant to first-line standard therapy and who are not candidates for radical surgery and\u002For localized therapy and who lack effective subsequent treatment.\n\nNotes:\n\n1. Standard treatment failure was defined as disease relapse or progression during or within 6 months of completion of treatment with first-line chemotherapeutic agents (including high-dose methotrexate, doxorubicin, cisplatin, isocyclophosphamide, etc.);\n2. Requirement of treatment intolerance: means that the subject is unable to continue the current effective systemic regimen due to the development of toxic side effects such as ≥ grade 3 vomiting, diarrhea, abdominal pain, myelosuppression, etc., and that refusal is not accepted for financial and personal reasons;\n3. The standard treatment received by the subject must be in accordance with the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Treatment of Bone and Soft Tissue Tumors, 2023 Edition; 4. At least one measurable target lesion according to RECIST 1.1 criteria; 5. Subjects must provide a tumor tissue sample (paraffin block or number of unstained sections meeting the testing requirements specified by the Institute) within 2 years that meets the requirements to be tested by immunohistochemistry for GPC3 and CD40 and needs to be positive for GPC3 expression;; 6. Karnofsky functional status score ≥60; 7. Expected survival ≥ 12 weeks; 8. Laboratory tests should meet at least the indicators specified below:\n\n1)Absolute neutrophil count (ANC) ≥ 1.5 x 10\\^9\u002FL; 2)Absolute lymphocyte cell count (LY) ≥ 0.6 x 10\\^9\u002FL; 3)Lymphocytes make up ≥10% of white blood cells; 4)Platelets ≥75 x 10\\^9\u002FL; 5)Hemoglobin ≥ 90 g\u002FL; 6)Creatinine clearance ≥60 ml\u002Fmin; 7)Serum bilirubin ≤ 1.5 times the upper limit of normal; if liver metastases are present, serum bilirubin ≤ 3.0 times the upper limit of normal; 8)Prolongation of prothrombinogen time ≤ 4s; 9)≤ 2.5 times the upper limit of normal for albumin transaminase (AST) and albumin transaminase (ALT); if liver metastases are present, ALT and\u002For AST ≤ 5.0 times the upper limit of normal; 9. Left ventricular ejection fraction was \\>50%; 10. Oxygen saturation \\>92% in the non-oxygenated state; 11. Women of childbearing potential who had a negative blood pregnancy test prior to the start of the trial and who agreed to use effective contraception for the duration of the trial up to the last follow-up visit; male subjects whose partners were of childbearing potential agreed to use effective contraception for the duration of the trial up to the last follow-up visit; 12. Vascular access is adequate for cell collection, and lines are available for subjects with existing central venous catheters; 13. I or my legal guardian\u002Fproxy agree to participate in this trial and sign the informed consent form.\n\nExclusion Criteria:\n\n1. Presence of brain metastases;\n2. Subjects who have previously received or are awaiting an organ transplant;\n3. Toxicity due to prior therapy not stabilized or recovered to ≤ grade 1 (except in cases judged by the investigator to be not clinically significant);\n4. Autoimmune diseases requiring systemic immunosuppressive therapy, such as systemic lupus erythematosus, rheumatoid arthritis, and ulcerative colitis, within 2 years prior to the start of screening;\n5. Use of any of the following medications or treatments during the designated time period prior to cell collection:\n\n   1. Surgical treatment, interventional therapy, radiotherapy, ablation, and other localized treatments for the study disease within 4 weeks prior to cell collection;\n   2. Subjects who have had major surgery or significant trauma within 4 weeks prior to cell collection, or who are expected to require major surgery during the study period;\n   3. Immunotherapy with anti-PD1, PD-L1, etc. within 4 weeks prior to cell collection;\n   4. Therapeutic doses of corticosteroids have been used within 3 days prior to cell collection. However, topical and inhaled steroids are permitted;\n6. Other untreated malignant tumors within the previous 5 years or concurrently, except cervical cancer in situ, basal cell carcinoma of the skin, and ductal carcinoma in situ of the breast;\n7. Previously treated with targeted GPC3 therapy (can be enrolled if still positive for GPC3 expression upon testing);\n8. Those who have previously received other cellular therapy or genetically modified cellular therapy, such as TCR-T therapy, CAR-T therapy, etc;\n9. Prior or clinically significant CNS disorders at screening, such as epilepsy, seizures, cerebrovascular disease (ischemia\u002Fhemorrhage\u002Finfarction), cerebral edema, reversible posterior leukoencephalopathy, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disorders, organic brain syndromes, or psychiatric disorders;\n10. Presence of chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), and clinically significant pulmonary function test abnormalities;\n11. Subjects assessed by the investigator as having a significant amount of plasmapheresis (e.g., pleural effusion, peritoneal effusion, pericardial effusion) that cannot be controlled with treatment;\n12. Medication-uncontrolled hypertension (systolic blood pressure \\>160 mmHg and\u002For diastolic blood pressure \\>90 mmHg) or the presence of clinically significant (e.g., active) cardiovascular disease, such as cerebrovascular accident, myocardial infarction, unstable angina pectoris, or severe cardiac arrhythmia that is uncontrolled with medication or that has a potential impact on the study treatment in the 6 months prior to the date of signing of the informed consent;\n13. Subjects who are positive for Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) and have a peripheral blood HBV-DNA test higher than the lower limit of detection (HBsAg-positive but with a peripheral blood HBV-DNA test lower than the lower limit of detection according to the Guidelines for the Prevention and Treatment of Chronic Hepatitis B, Version 2022, at least at least 4 weeks of antiviral therapy is required prior to the first administration of the investigational drug, and during the course of the study Ongoing antiviral therapy for 6-12 months with monitoring of HBV DNA, HBsAg, and ALT levels every 1-3 months); Hepatitis C virus (HCV) antibody positive and peripheral blood HCV-RNA test above the lower limit of detection; HIV antibody positive; syphilis antibody positive;\n14. Active EBV and cytomegalovirus, defined as subjects with IgM antibody-positive or IgM antibody-negative EBV serum but higher-than-normal EBV-DNA; and cytomegalovirus (CMV) serum IgM antibody-positive or IgM antibody-negative cytomegalovirus but higher-than-normal CMV-DNA;\n15. Abnormalities of cardiac function include: long QTc syndrome or QTc interval \\>480 ms; complete left bundle branch block, degree II\u002FIII AV block; severe, uncontrolled arrhythmia requiring pharmacologic therapy; history of chronic congestive heart failure with NYHA class ≥3 (refer to Appendix 3) cardiac ejection fraction less than 50% in the 6 months prior to screening; CTCAE ≥3 grade heart valve disease; myocardial infarction, cardiac angioplasty or stenting, unstable angina, history of severe pericardial disease, or other clinically significant cardiac disease within 6 months prior to screening;\n16. Subjects requiring anticoagulation therapy;\n17. Subjects requiring long-term antiplatelet therapy;\n18. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months prior to initiation of screening;\n19. Infections (fungal, bacterial, viral, or other) that require intravenous antimicrobial control or are uncontrollable, for simple urinary tract infections, and for bacterial pharyngitis, may be enrolled if the investigator evaluates that they can be controlled by curative treatment;\n20. The presence of any factors affecting compliance with the protocol, or the unwillingness or inability of the subject to comply with the procedures required in the study protocol, as judged by the investigator.","16 Years",{"count":257,"type":21},9,[24],"The purpose of this study, a single-center, open, single-dose clinical study, was to evaluate the safety, tolerability, and pharmacokinetic profile of IM83 CAR-T cells in the treatment of patients with relapsed or refractory osteosarcoma",[30,101],[262,263],"IM83 CAR-T","Relapsed or refractory osteosarcoma","2024-05-10",{"date":266,"type":43},"2024-05-14",{"date":268,"type":21},"2024-06-15",{"date":270,"type":21},"2026-06-15",{"name":272,"class":273},"Beijing Immunochina Medical Science & Technology Co., Ltd.","INDUSTRY"]