[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"recurrent-osteosarcoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:recurrent-osteosarcoma":32},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,8,0,[8,49,104,140,164,191,218,249],{"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":26,"conditions":27,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":37,"lastUpdatePostDateStruct":38,"startDateStruct":41,"completionDateStruct":43,"leadSponsor":45,"locationsCount":48},"100054232","phase-1-trastuzumab-deruxtecan-ds-8201a-for-the-treatment-of-newly-diagnosed-recurrent-or-refractory-osteosarcoma-wilms-tumor-and-desmoplastic-small-round-cell-tumor-100054232",false,"NCT04616560","Trastuzumab Deruxtecan (DS-8201a) for the Treatment of Newly Diagnosed, Recurrent or Refractory Osteosarcoma, Wilms Tumor, and Desmoplastic Small Round Cell Tumor","A Phase 1\u002F2 Study of DS-8201a (NSC# 807708) in Children, Adolescents, or Young Adults With Recurrent Osteosarcoma, Wilms Tumor, and Desmoplastic Small Round Cell Tumor","Inclusion Criteria:\n\n* Phase 1 (Part A): Patients must be at least 2 years and less than 12 years of age at the time of study enrollment\n* Phase 2: Wilms tumor patients (Part B1): All Wilms tumor patients enrolled must be less than 18 years of age at enrollment\n\n  * Until the completion of the Phase 1 dose confirmation, patients must be at least 12 years of age and less than 18 years of age at the time of study enrollment\n  * Following dose confirmation of DS-8201a in children at least 2 to less than 12 years old in the Phase 1 component, Wilms tumor patients at least 2 to less than 18 years of age will be allowed on the Phase 2 component\n* Phase 2: DSRCT patients (Part B2): Until the completion of the Phase 1 component, patients enrolling on the Phase 2 component of the study must be from at least 12 to 39 years of age at the time of study enrollment\n\n  * Following dose confirmation of DS-8201a in children at least 2 to less than 12 years old in the Phase 1 component, DSRCT patients at least 2 to 39 years of age will be allowed on the Phase 2 component\n* Patients must have had histologic verification of Wilms tumor or desmoplastic small round cell tumor at original diagnosis or relapse\n* Solid tumors: Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Patients with clinically inactive brain metastases may be included in the study. Patients with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. Lastly, patient must have unresectable lesions or lesions with no intention to surgically remove the lesions in the 6 months following enrollment\n* Wilms tumor: WT patients must have either refractory disease or a very high risk relapse, defined as ANY of the following:\n\n  * Relapse after initial treatment with 4 or more chemotherapy agents (e.g. Regimens vincristine, dactinomycin, doxorubicin, cyclophosphamide, etoposide and radiation \\[M\\], vincristine, dactinomycin and doxorubicin, vincristine, and irinotecan \\[MVI\\], doxorubicin, vincristine, cyclophosphamide, carboplatin, etoposide and radiation \\[UH-1\\], doxorubicin, vincristine, cyclophosphamide, carboplatin, etoposide, vincristine, and irinotecan \\[UH-2\\], vincristine, irinotecan, cyclophosphamide, carboplatin, etoposide and doxorubicin \\[UH-3\\], and etoposide, carboplatin, cyclophosphamide, and doxorubicin \\[HR-1\\])\n  * Relapse with high risk histology (anaplasia, blastemal predominant)\n  * Multiple relapses\n* Desmoplastic small round cell tumor: DSRCT patients with relapsed or refractory disease are eligible\n* Patient's current disease state must be one for which they have received at least standard initial therapy, defined as systemic therapy combined with either radiation or surgery for local control of the primary tumor at diagnosis. Prior therapy after relapse is not required\n* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0 or 1. Use Karnofsky for patients older than 16 years of age and Lansky for patients 16 years of age and younger\n* Patients must have 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: For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment\n\n    * \\>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)\n  * Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \\[ANC\\] counts): \\>= 7 days after the last dose of agent\n  * Antibodies: \\>= 4 weeks (28 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\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: \\>= 30 days\n  * Cellular therapy: \\>= 30 days after the completion the infusion of any type of cellular therapy (e.g., modified T cells, natural killer \\[NK\\] cells, dendritic cells, etc.)\n  * Radiation therapy (XRT)\u002Fexternal beam irradiation including protons: \\>= 4 weeks (28 days) including palliative radiation therapy to the chest. \\>= 14 days after palliative local XRT to areas other than the chest or for whole brain radiotherapy\n  * Radiopharmaceutical therapy (e.g., radiolabeled antibody, samarium): \\>= 42 days after systemically administered radiopharmaceutical therapy\n  * Patients must not have received prior HER2 therapies including antibody drug conjugates (e.g. TDM-1 or DS-8201a), HER2 directed cellular therapies, HER2 receptor therapy (e.g. trastuzumab, pertuzumab, margetuximab, zanidatamab, zenocutuzumab) or small molecule antagonists of HER2 (e.g lapatinib, tucatinib, or neratinib). Prior exposure to antibody drug conjugates which do not target HER2 as well as prior treatment with topoisomerase 1 inhibitors (e.g. irinotecan, topotecan) are permitted\n* Patients must be at least 14 days from the date of last surgery\n* Peripheral absolute neutrophil count (ANC) \\>= 1000\u002FuL, (for patients with solid tumors without known bone marrow involvement)\n* Platelet count \\>= 100,000\u002FuL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (for patients with solid tumors without known bone marrow involvement)\n* Hemoglobin \\>= 8.0 g\u002FdL at baseline (Red Blood Cell transfusion is not allowed within 1 week prior to enrollment) (for patients with solid tumors without known bone marrow involvement)\n* For patients less than or equal to 17 years old, \"Bedside\" Schwartz formula (2009)\n* Estimated glomerular filtration rate (GFR) (eGFR) ≥ 70 mL\u002Fmin\u002F1.73 m\\^2 (\\> 70mL\u002Fmin\u002F1.73 m\\^2 for patients \\> 17 years old)\n\n  * For patients older than 17 years of age the Cockroft-Gault equation should be utilized to calculate creatinine clearance ≥ 70 ml\u002Fmin:\n  * OR for any age group:\n\n    * A 24 hour urine creatinine clearance ≥ 70 mL\u002Fmin\u002F1.73 m\\^2 (\\> 70mL\u002Fmin for patients ≥ 17 years old) OR\n    * A directly measured GFR ≥ 70 mL\u002Fmin\u002F1.73 m\\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)\n* Bilirubin (sum of conjugated + unconjugated or total) =\\\u003C 1.5 x upper limit of normal (ULN) for age. For patients with documented Gilbert's syndrome (unconjugated hyperbilirubinemia) bilirubin must be \\\u003C 3 x ULN for age (patients with solid tumors)\n* Aspartate aminotransferase (AST) =\\\u003C 3 x ULN\n* Serum albumin \\>= 2.5 g\u002FdL (patients with solid tumors)\n* International normalized ratio (INR)\u002Fprothrombin time (PT) =\\\u003C 1.5 x ULN. Exception for patients receiving coumarin-derivative anticoagulants or other similar anticoagulant therapy, who must have INR\u002FPT within the therapeutic range as deemed appropriate by the investigator\n* Shortening fraction of \\>= 27% by echocardiogram, or ejection fraction of \\>= 50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before Step 1 enrollment\n* Corrected QT interval (QTc) prolongation to \\\u003C 480 ms based on average triplicate 12-lead electrocardiogram (ECG)\n* Pulse oximetry \\> 93% on room air\n* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days\n* Nervous system disorders (Common Terminology Criteria for Adverse Events \\[CTCAE\\] version \\[v\\]5) resulting from prior chemotherapy, surgery, and\u002For radiation must be =\\\u003C grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible\n* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of enrollment are eligible\n* All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines\n\nExclusion Criteria:\n\n* Pregnant, planning to become 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 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 and upon completion of the study and for at least 7 months for females and 4 months for males after the last dose of study drug. Abstinence is an acceptable method of birth control\n\n  * Methods considered as highly effective methods of contraception include:\n\n    * Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:\n\n      * Oral\n      * Intravaginal\n      * Transdermal\n    * Progestogen-only hormonal contraception associated with inhibition of ovulation:\n\n      * Oral\n      * Injectable\n      * Implantable\n    * Intrauterine device (IUD)\n    * Intrauterine hormone-releasing system (IUS)\n    * Bilateral tubal occlusion\n    * Vasectomized partner\n    * Complete sexual abstinence defined as refraining from heterosexual intercourse. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception\n* Non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \\[FSH\\] \\> 40 mIU\u002FmL and estradiol \\\u003C 40 pg\u002FmL \\[\\\u003C 147 pmol\u002FL\\] is confirmatory). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method\n* Male patients must not freeze or donate sperm starting at enrollment and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to enrolment in this study\n* Female patients must not donate, or retrieve for their own use, ova from the time of enrollment and throughout the study treatment period, and for at least 7 months after the final study drug administration\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 receiving chloroquine or hydroxychloroquine within 14 days are not eligible for this trial\n* Patients who received a live, attenuated vaccine (messenger ribonucleic acid \\[mRNA\\] and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to enrollment are not eligible for this trial\n\n  * Note: Participants, if enrolled, should not receive live vaccines during the study and up to 90 days after the last dose of study intervention. It is recommended that patients receive a yearly influenza killed vaccination and additional killed vaccinations based on local or national recommendations. Consider vaccination against viral pathogens that cause pneumonias according to local or national guidelines\n* Patients who have received a prior solid organ transplantation are not eligible\n* Patients with a medical history of myocardial infarction within 180 days before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV) or troponin levels consistent with myocardial infarction as defined according to the manufacturer 28 days prior to enrollment are not eligible\n* Additionally, patients with a history of any of the following congenital heart disease are not eligible:\n\n  * Single ventricle heart defects (hypoplastic left heart syndrome, unbalanced atrioventricular septal defects, double inlet left ventricle, tricuspid atresia, the presence of superior cavopulmonary anastomosis or Fontan palliation);\n  * Unpalliated defects with significant hemodynamic alterations or palliated lesions with residual hemodynamic alterations (ductal-dependent or shunt-dependent physiology, large unrestrictive ventricular septal defect, transposition of the great arteries, greater than moderate atrioventricular valve insufficiency, moderate or greater aortic valve stenosis, moderate or greater aortic valve insufficiency, large atrial septal defects with significant right ventricular volume overload, large patent ductus arteriosus)\n* Patients who have a pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART) are not eligible. (Drainage and concentrated ascites reinfusion therapy are not allowed within 2 weeks prior to enrollment)\n* Patients who have spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms are not eligible\n* Patients with a known history of severe hypersensitivity to DS-8201a, any excipient contained in the DS-8201a drug formulation, or HER2-targeted monoclonal antibodies (trastuzumab, pertuzumab, margetuximab) are not eligible\n* Patients who have an uncontrolled infection or non-healing surgical site are not eligible\n* Patients with a known history of substance abuse or any other clinically significant medical conditions (i.e. psychological conditions) that may, in the opinion of the investigator, interfere with the patient's participation in the clinical study or evaluation of the clinical study results are not eligible\n* Patients who have pulmonary compromise, ex hypoxia, resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e. pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion etc.), or prior pneumonectomy are not eligible\n* Patients who have a history of (non-infectious) ILD (interstitial lung disease)\u002Fpneumonitis that required steroids, has current ILD\u002Fpneumonitis, or for whom suspected ILD\u002Fpneumonitis cannot be ruled out by imaging at screening are not eligible. Patients who have history of genetic disorders of the lung (i.e. cystic fibrosis 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\n* Patients with known hepatitis B or C with detectable viral load are not eligible\n* Patients with any autoimmune, connective tissue or inflammatory disorders (e.g., rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of enrollment or genetic diseases involving the lung are not eligible\n* Patients with an active primary immunodeficiency are not eligible","ALL","12 Years","39 Years",{"count":20,"type":21},55,"ESTIMATED","INTERVENTIONAL",[24,25],"PHASE1","PHASE2","This phase I\u002FII trial studies the effects of trastuzumab deruxtecan (DS-8201a) in treating patients with osteosarcoma, Wilms tumor (WT) or desmoplastic small round cell tumor (DSRCT) that is newly diagnosed or has come back after a period of improvement (recurrent) or that has not responded to previous treatment (refractory). Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them.",[28,29,30,31,32,33,34,35],"Desmoplastic Small Round Cell Tumor","Osteosarcoma","Recurrent Desmoplastic Small Round Cell Tumor","Recurrent Kidney Wilms Tumor","Recurrent Osteosarcoma","Refractory Desmoplastic Small Round Cell Tumor","Refractory Wilms Tumor","Wilms Tumor","RECRUITING","2026-07-10",{"date":39,"type":40},"2026-07-13","ACTUAL",{"date":42,"type":40},"2021-03-08",{"date":44,"type":21},"2027-12-31",{"name":46,"class":47},"National Cancer Institute (NCI)","NIH",28,{"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":22,"phases":60,"briefSummary":61,"conditions":62,"keywords":84,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":93,"lastUpdatePostDateStruct":94,"startDateStruct":96,"completionDateStruct":98,"leadSponsor":100,"locationsCount":103},"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","30 Years",{"count":59,"type":21},90,[24,25],"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.",[63,64,65,66,67,68,32,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83],"Recurrent Solid Tumor","Recurrent Ewing Sarcoma","Recurrent Hepatoblastoma","Recurrent Malignant Germ Cell Tumor","Recurrent Malignant Solid Neoplasm","Recurrent Neuroblastoma","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 Neuroblastoma","Refractory Osteosarcoma","Refractory Peripheral Primitive Neuroectodermal Tumor","Refractory Rhabdoid Tumor","Refractory Rhabdomyosarcoma","Refractory Soft Tissue Sarcoma",[85,86,87,88,89,90,91,92],"Pediatric Cancer","Childhood Cancer","Ewing Sarcoma","PARP inhibitor","Solid tumor","Irinotecan","Onivyde","Talazoparib","2026-05-18",{"date":95,"type":40},"2026-05-19",{"date":97,"type":40},"2021-06-09",{"date":99,"type":21},"2026-12-31",{"name":101,"class":102},"St. Jude Children's Research Hospital","OTHER",10,{"id":105,"slug":106,"hasResults":11,"nctId":107,"briefTitle":108,"officialTitle":109,"acronym":4,"eligibilityCriteria":110,"healthyVolunteers":11,"sex":16,"minAge":56,"maxAge":57,"enrollmentInfo":111,"targetDuration":4,"studyType":22,"phases":113,"briefSummary":114,"conditions":115,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":129,"lastUpdatePostDateStruct":130,"startDateStruct":132,"completionDateStruct":134,"leadSponsor":136,"locationsCount":139},"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":112,"type":21},147,[24,25],"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.",[116,117,118,119,120,121,122,64,65,123,67,124,32,125,74,75,126,77,127,79,128,35],"Colorectal Carcinoma","Endometrial Carcinoma","Melanoma","Neuroblastoma","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","2026-05-01",{"date":131,"type":40},"2026-05-05",{"date":133,"type":40},"2021-11-08",{"date":135,"type":21},"2028-06-30",{"name":137,"class":138},"Children's Oncology Group","NETWORK",21,{"id":141,"slug":142,"hasResults":11,"nctId":143,"briefTitle":144,"officialTitle":145,"acronym":4,"eligibilityCriteria":146,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":147,"targetDuration":4,"studyType":22,"phases":149,"briefSummary":150,"conditions":151,"keywords":4,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":155,"lastUpdatePostDateStruct":156,"startDateStruct":158,"completionDateStruct":160,"leadSponsor":161,"locationsCount":163},"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",{"count":148,"type":21},40,[25],"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.",[152,153,32,79,154],"Locally Advanced Osteosarcoma","Metastatic Osteosarcoma","Unresectable Osteosarcoma","2026-04-15",{"date":157,"type":40},"2026-04-17",{"date":159,"type":40},"2023-04-25",{"date":44,"type":21},{"name":162,"class":102},"M.D. Anderson Cancer Center",2,{"id":165,"slug":166,"hasResults":11,"nctId":167,"briefTitle":168,"officialTitle":169,"acronym":4,"eligibilityCriteria":170,"healthyVolunteers":11,"sex":16,"minAge":171,"maxAge":172,"enrollmentInfo":173,"targetDuration":4,"studyType":22,"phases":175,"briefSummary":176,"conditions":177,"keywords":179,"overallStatus":36,"whyStopped":4,"lastUpdateSubmitDate":181,"lastUpdatePostDateStruct":182,"startDateStruct":184,"completionDateStruct":186,"leadSponsor":188,"locationsCount":190},"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","1 Year","75 Years",{"count":174,"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.",[178,32,79],"Advanced Osteosarcoma",[180],"Bones and Joints","2026-02-09",{"date":183,"type":40},"2026-02-11",{"date":185,"type":40},"2026-01-16",{"date":187,"type":21},"2044-01-31",{"name":189,"class":102},"Fred Hutchinson Cancer Center",1,{"id":192,"slug":193,"hasResults":11,"nctId":194,"briefTitle":195,"officialTitle":196,"acronym":4,"eligibilityCriteria":197,"healthyVolunteers":11,"sex":16,"minAge":198,"maxAge":4,"enrollmentInfo":199,"targetDuration":4,"studyType":22,"phases":201,"briefSummary":202,"conditions":203,"keywords":204,"overallStatus":207,"whyStopped":4,"lastUpdateSubmitDate":208,"lastUpdatePostDateStruct":209,"startDateStruct":211,"completionDateStruct":213,"leadSponsor":215,"locationsCount":190},"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":200,"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",[79,32],[205,206],"IM83 CAR-T","Relapsed or refractory osteosarcoma","NOT_YET_RECRUITING","2024-05-10",{"date":210,"type":40},"2024-05-14",{"date":212,"type":21},"2024-06-15",{"date":214,"type":21},"2026-06-15",{"name":216,"class":217},"Beijing Immunochina Medical Science & Technology Co., Ltd.","INDUSTRY",{"id":219,"slug":220,"hasResults":11,"nctId":221,"briefTitle":222,"officialTitle":223,"acronym":4,"eligibilityCriteria":224,"healthyVolunteers":11,"sex":16,"minAge":225,"maxAge":172,"enrollmentInfo":226,"targetDuration":4,"studyType":22,"phases":228,"briefSummary":229,"conditions":230,"keywords":234,"overallStatus":207,"whyStopped":4,"lastUpdateSubmitDate":240,"lastUpdatePostDateStruct":241,"startDateStruct":243,"completionDateStruct":245,"leadSponsor":247,"locationsCount":190},"100519280","phase-2-adjuvant-therapy-for-high-risk-hepatocellular-carcinoma-post-liver-transplantation-100519280","NCT06041490","Adjuvant Therapy for High-risk Hepatocellular Carcinoma Post Liver Transplantation","A Randomized, Controlled, Open-label, Multi-center Clinical Trial of Multi-kinase Inhibitor Combined With Bevacizumab as Adjuvant Therapy in Patients With Hepatocellular Carcinoma and High-risk Recurrence Factors After Liver Transplantation","Inclusion Criteria:\n\n1. Voluntary enrollment, accompanied by the signing of a written informed consent form, is a prerequisite for participation in this study. This ensures that participants enter the study based on their own decision and understanding of the research objectives, procedures, and potential risks.\n2. The study includes individuals aged between 18 and 75 years, inclusive, without any gender restrictions. This broad age range and gender inclusivity allow for a diverse representation of participants, facilitating a comprehensive understanding of the study outcomes across different demographic profiles.\n3. Prior to enrollment, participants must have undergone liver transplantation within the preceding 4 to 8 weeks. This specific time frame serves as an inclusion criterion to ensure that participants have recently undergone the surgical procedure, enabling researchers to investigate the effects of the transplantation within a relevant timeframe.\n4. Participants must have a confirmed pathological diagnosis of hepatocellular carcinoma (HCC) and meet at least one of the following criteria:\n\n   a) Pre-operative imaging or post-operative pathological confirmation of exceeding the Milan criteria.\n\n   b) Presence of major vascular invasion. c) Post-operative pathological confirmation of the presence of microvascular invasion (MVI).\n\n   d) Pre-operative imaging or post-operative pathological confirmation of the presence of satellite nodules.\n\n   e) Recurrence of HCC after liver resection and subsequent liver transplantation.\n5. Participants should have an anticipated life expectancy of more than 3 months.\n6. Participants should not have received systemic anti-tumor treatment prior to liver transplantation, with the exception of pre-operative transarterial chemoembolization (TACE), traditional Chinese medicine, and interferon treatment.\n7. Participants should have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1, indicating good functional status.\n8. Participants' liver function, as assessed by the Child-Pugh score, should be classified as Grade A, indicating well-preserved liver function.\n9. HBsAg-positive patients should receive continuous antiviral therapy post-transplantation, using first-line antiviral drugs such as entecavir, tenofovir, or tenofovir alafenamide.\n10. Participants should have adequate hematological and organ function, based on the laboratory test results obtained within 14 days before the initiation of the study treatment, as follows:\n\n    Laboratory tests (unless otherwise specified, no blood transfusion or use of G-CSF within 14 days prior to screening):\n    1. Hemoglobin ≥ 90 g\u002FL.\n    2. White blood cell count ≥ 3.0 x 10\\^9\u002FL.\n    3. Absolute neutrophil count (ANC) ≥ 1.5 x 10\\^9\u002FL.\n    4. Platelet count ≥ 75 x 10\\^9\u002FL.\n\n       Biochemical tests (no use of albumin within 14 days prior to screening):\n    5. Serum albumin ≥ 28 g\u002FL.\n    6. Total bilirubin ≤ 2 times the upper limit of normal (ULN).\n    7. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 times ULN.\n    8. Alkaline phosphatase (ALP) ≤ 5 times ULN.\n    9. Creatinine ≤ 1.5 times ULN or creatinine clearance (CrCl) \\> 50 mL\u002Fmin (calculated using the standard Cockcroft-Gault formula):\n\n       \\- For females: CrCl = ((140 - age) x body weight (kg) x 0.85) \u002F (72 x serum creatinine \\[mg\u002FdL\\]).\n       * For males: CrCl = ((140 - age) x body weight (kg) x 1.00) \u002F (72 x serum creatinine \\[mg\u002FdL\\]).\n\n       Coagulation Function:\n    10. International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 times the Upper Limit of Normal (ULN) or PT prolongation ≤ 6 seconds.\n    11. Activated Partial Thromboplastin Time (APTT) ≤ 1.5 times ULN.\n11. Women of Childbearing Potential: Women who agree to abstain from heterosexual intercourse during the treatment period and for at least 6 months after the last dose of the study drug, or use a contraceptive method with a failure rate of less than 1% per year. For women who have experienced menstrual bleeding and have not reached a postmenopausal state (continuous absence of menstruation for ≥12 months without any other known cause) and have not undergone sterilization procedures (removal of ovaries and\u002For uterus), they are considered to be of childbearing potential.\n\n    1. Examples of contraceptive methods with a failure rate of less than 1% per year include bilateral tubal ligation, male sterilization, hormone-based contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.\n    2. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial, patients' preferred lifestyle, and daily activities. Periodic abstinence methods (such as calendar-based methods, ovulation period methods, symptothermal methods, or post-ovulation methods) and withdrawal are not acceptable contraceptive methods.\n12. Men: Men who agree to abstain from heterosexual intercourse or use contraception and also agree not to donate sperm, as defined below:\n\n    1. If the female partner is of childbearing potential, male patients must abstain from heterosexual intercourse during the treatment period and for 6 months after the last dose of the study drug or use a condom plus another contraceptive method to achieve a contraceptive failure rate of \\\u003C1% per year. During the same period, male patients must also agree not to donate sperm. If the female partner is already pregnant, male patients must abstain from heterosexual intercourse or use a condom for contraception during the treatment period and for 6 months after the last dose of the study drug to avoid potential effects on the fetus.\n    2. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial, patients' preferred lifestyle, and daily activities. Periodic abstinence methods (such as calendar-based methods, ovulation period methods, symptothermal methods, or post-ovulation methods) and withdrawal are not acceptable contraceptive methods.\n\nExclusion Criteria:\n\nAccording to the information provided, the following patients are not eligible for participation in this study.\n\n1. Patients with a previous histological\u002Fcytological diagnosis of fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, or other similar components.\n2. Patients with a history of malignancies other than hepatocellular carcinoma, unless they meet the following criteria:\n\n   1. Patients who have undergone potentially curative treatment and have no evidence of the disease within the past 5 years.\n   2. Patients who have successfully undergone resection of basal cell carcinoma, squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, or other in situ carcinomas; or patients who have been treated for superficial bladder cancer, have undergone surgical treatment, and have prostate-specific antigen (PSA) tumor markers within the normal range.\n3. Patients who are concurrently taking medications that may prolong the QTc interval and\u002For induce torsades de pointes (Tdp) or medications that affect drug metabolism.\n\n   Patients with a known or suspected history of allergies to sorafenib, lenvatinib, donafenib, or similar drugs.\n4. Patients with active bleeding or coagulation abnormalities, bleeding tendencies, or those undergoing thrombolysis, anticoagulant therapy, or antiplatelet therapy.\n5. Patients who have experienced thrombosis or thromboembolic events within the past 6 months, such as stroke and\u002For transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc.\n\n7.Patients who have experienced esophageal or gastric variceal bleeding due to portal hypertension within the past 6 months or any life-threatening bleeding event within the past 3 months. Patients with a history of gastrointestinal bleeding within the past 6 months or clear evidence of gastrointestinal bleeding tendencies, such as high-risk esophageal varices, locally active gastrointestinal ulcers, fecal occult blood ≥(++), are not eligible for inclusion. If fecal occult blood is (+), a gastroscopy examination is required. Evidence or history of bleeding mechanism disorders with ≥3 grade (CTC-AE 5.0) bleeding events, etc.\n\n8.Patients with clinically significant cardiovascular diseases, including but not limited to acute myocardial infarction within the past 6 months, severe\u002Funstable angina or coronary artery bypass grafting, congestive heart failure (NYHA class \\>2), poorly controlled or requiring pacemaker therapy for arrhythmias, poorly controlled hypertension (systolic blood pressure ≥140 mmHg and\u002For diastolic blood pressure ≥90 mmHg) despite medication.\n\n9.Other significant clinical and laboratory abnormalities that the investigator deems to impact safety assessment, such as uncontrolled diabetes, chronic kidney disease, peripheral neuropathy of grade II or higher (CTCAE V5.0), thyroid dysfunction, etc.\n\n10.Active or poorly controlled severe infections, including:\n\n1. HIV-positive (HIV1\u002F2 antibody).\n2. Active hepatitis B (positive for HBsAg or HBV DNA\\>2000 IU\u002Fml and abnormal liver function).\n3. Active hepatitis C (positive for HCV antibody or HCV RNA≥103 copies\u002Fml and abnormal liver function).\n4. Active tuberculosis.\n5. Other uncontrolled active infections (CTCAE V5.0 \\>2 grade). 11.Patients who have not yet recovered from surgery, with unhealed wounds or severe postoperative complications.\n\n   12.Patients with substance abuse or any medical, psychological, or social conditions that may affect the study, patient compliance, or potentially endanger patient safety.\n\n   13.Patients who have received treatment with potent CYP3A4 inhibitors (such as clarithromycin, indinavir, ketoconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole, etc.) within 7 days prior to study participation or potent CYP3A4 inducers (such as phenytoin, phenobarbital, primidone, carbamazepine, rifampin, rifabutin, rifapentine, St. John's wort, etc.) within 12 days prior to study participation.\n\n   14.Recipients of multiorgan transplantation. 15.Development of distant metastasis within 1 month after transplantation. 16.Participation in another clinical trial within the past 30 days. 17.Incomplete treatment duration of less than 3 months. 18.The investigator's comprehensive judgment deems the patient unsuitable for participation in this study.","18 Years",{"count":227,"type":21},88,[25],"1. Explore the impact of postoperative administration of multi-kinase inhibitors (including sorafenib, lenvatinib, and regorafenib) in conjunction with bevacizumab on post-transplant recurrence, overall survival, and drug safety in liver transplant recipients at high risk of recurrence in hepatocellular carcinoma.\n2. The primary objective of this study is to evaluate the efficacy of multi-kinase inhibitors in combination with bevacizumab as adjuvant therapy in liver transplant recipients with hepatocellular carcinoma who present high-risk factors for recurrence, based on the one-year recurrence-free survival rate (1-year RFS rate).\n3. The secondary objectives of this study are to assess the effectiveness and safety of multi-kinase inhibitors in combination with bevacizumab as adjuvant therapy in liver transplant recipients with hepatocellular carcinoma who present high-risk factors for recurrence, based on the following parameters: Recurrence-free survival (RFS) duration, Overall survival (OS), Two-year and three-year RFS rates, Graft survival, Quality of life evaluation (QoL), Incidence of adverse events and serious adverse events.",[231,232,32,233],"Liver Transplant; Complications","Hepatocarcinoma","High-Risk Cancer",[232,235,236,237,238,239],"Liver Transplant","Recurrence","High-Risk","multikinase inhibitor","bevacizumab","2023-09-11",{"date":242,"type":40},"2023-09-18",{"date":244,"type":21},"2023-09",{"date":246,"type":21},"2027-01",{"name":248,"class":102},"Peking Union Medical College Hospital",{"id":250,"slug":251,"hasResults":11,"nctId":252,"briefTitle":253,"officialTitle":254,"acronym":255,"eligibilityCriteria":256,"healthyVolunteers":11,"sex":16,"minAge":4,"maxAge":4,"enrollmentInfo":257,"targetDuration":259,"studyType":260,"phases":4,"briefSummary":261,"conditions":262,"keywords":4,"overallStatus":207,"whyStopped":4,"lastUpdateSubmitDate":287,"lastUpdatePostDateStruct":288,"startDateStruct":290,"completionDateStruct":292,"leadSponsor":294,"locationsCount":4},"100478829","registry-for-children-adolescents-and-adults-with-osteosarcoma-and-biologically-related-bone-sarcomas-100478829","NCT05515068","Registry For Children, Adolescents And Adults With Osteosarcoma And Biologically Related Bone Sarcomas","Registry For Children, Adolescents And Adults With Osteosarcoma And Biologically Related Bone Sarcomas (COSS-Registry)","COSS-Registry","Inclusion Criteria:\n\n* high-grade osteosarcoma (conventional and non-conventional)\n* parosteal, periosteal or extraosseous osteosarcoma\n* low grade central osteosarcoma\n* (osseous) Undifferentiated pleomorphic sarcoma (UPS)\n* (osseous) leiomyosarcoma\n* (osseous) dedifferentiated chondrosarcoma\n* (osseous) mesenchymal chondrosarcoma\n* (osseous) fibrosarcoma\n* (osseous) angiosarcoma\n* informed consent\n\nExclusion Criteria:\n\n* no informed consent",{"count":258,"type":21},1000,"20 Years","OBSERVATIONAL","The Registry For Children, Adolescents And Adults With Osteosarcoma And Biologically Related Bone Sarcomas (COSS-Registry) is a non-interventional, multicentric, international, clinical and epidemiologic patient registry. The COSS-Registry collects key data on osteosarcomas or biologically related bone sarcomas. With that data collection we want to gain new scientific insights and results about this tumor disease, prognosis, surveillance and long-term effects.\n\nBesides the data collection we would also like to foster the collection of biomaterial (tumor specimen and blood samples) for scientific research.\n\nThe stored material will be used to perform cell and molecular biological analyses to identify the causes of osteosarcoma, the prognosis and possible new treatment options.\n\nAs a starting point the donated biomaterial of registered patients will be analyzed firstly for the presence of a tumor predisposition by germline mutations.\n\nIn case of detected genetic variations that are related to the tumor disease and which may affect the patient's health and follow-up care (because of the potentially increased risk of developing other malignant tumors), affected patients will be informed and referred to genetic counseling.\n\nRegistry patients will be asked at the time of diagnosis if they wish to be informed about germline variants detected as part of the study procedures.",[29,263,264,265,266,267,268,269,270,271,272,273,274,275,276,277,278,279,32,280,281,282,283,284,285,286],"Bone Tumor","Bone Sarcoma","High Grade Sarcoma","Osteoblastic Osteosarcoma","Chondroblastic Osteosarcoma","Fibroblastic Osteosarcoma","Conventional Osteosarcoma","Conventional Central Osteosarcoma of Bone","Low Grade Central Osteosarcoma","Osseous Sarcoma","Osseous Tumor","Small Cell Osteosarcoma","Telangiectatic Osteosarcoma","Undifferentiated Pleomorphic Sarcoma","Parosteal Osteosarcoma","Periosteal Osteosarcoma","Extraskeletal Osteosarcoma","High Grade Surface Osteosarcoma","Osseous Angiosarcoma","Osseous Fibrosarcoma","Osseous Leiomyosarcoma","Osseous Dedifferentiated Chondrosarcoma","Osseous Mesenchymal Chondrosarcoma","Clear Cell Osteosarcoma","2022-08-24",{"date":289,"type":40},"2022-08-25",{"date":291,"type":21},"2022-09",{"date":293,"type":21},"2032-03",{"name":295,"class":102},"Klinikum Stuttgart"]