[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"refractory-malignant-solid-neoplasm\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:refractory-malignant-solid-neoplasm":30},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,11,0,[8,46,101,127,159,186,218,246,268,304,325],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":34,"lastUpdatePostDateStruct":35,"startDateStruct":38,"completionDateStruct":40,"leadSponsor":42,"locationsCount":45},"100500068","phase-1-au409-for-the-treatment-of-advanced-primary-liver-cancers-or-solid-tumor-with-liver-metastatic-disease-100500068",false,"NCT05791448","AU409 for the Treatment of Advanced Primary Liver Cancers or Solid Tumor With Liver Metastatic Disease","First in Human Dose Escalation Study of AU409 in Patients With Advanced Primary Liver Cancers or Advanced Solid Tumor With Liver Predominant Metastatic Disease","Inclusion Criteria:\n\n* Age \\>= 18 years old\n* Patients must have histopathologically \u002Fcytologically confirmed advanced solid tumor, which is refractory to standard therapeutic options, or for which there are no standard therapeutic options. Failure of all approved therapies that have a marginal impact on survival is not required as long as the treating physician considers that treatment on study is appropriate for the subject and documents that the subject elects to defer the approved therapies\n* During the dose-escalation portion, patients must have primary liver malignancy (including hepatocellular carcinoma or cholangiocarcinoma) OR a solid tumor with liver dominant disease; liver dominant disease is defined as the majority of the tumor burden being in the liver per investigator assessment AND no more than two extrahepatic sites of disease (site of disease refers to organ or system). During the dose expansion portion of the study, eligibility may be limited to one or more tumor types depending on findings from the dose-escalation phase; this will be clarified in an amendment\n* Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\n* Patient must have recovered from any toxic effects of previous chemotherapy, targeted therapy or radiotherapy as judged by the Investigator to =\\\u003C grade 1 (except for alopecia). Residual sensory neuropathy =\\\u003C grade 2 is allowed. Residual endocrine adverse events (such as hypothyroidism or hypoadrenalism) that are manageable with replacement therapy are allowed\n* Previous chemotherapy\u002Fradiotherapy\u002Ftargeted\u002Fimmunotherapy therapy should have been completed at least 4 weeks prior to start of AU409 administration, or five half-lives, whichever is shorter (except for palliative radiation therapy that should be completed \\>= 14 days prior to study entry)\n* Patients must have an estimated life expectancy of at least 3 months\n* Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation. A male participant must agree to use highly effective contraception during the intervention period and for 60 days after the last dose of AU409 and refrain from donating sperm during this period. WOCBP are eligible to participate if they are not pregnant, not breastfeeding, and agree to follow the contraceptive guidance during the study intervention period and for at least 90 days after the last dose of AU409\n\n  * Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately\n* A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)\n* Patients must agree, as part of the informed consent, to undergo liver biopsy (for a subset of patients enrolled at and above dose level 4) and to provide blood for pharmacokinetics analysis\n* Absolute neutrophil count (ANC) \\>= 1500\u002Fmm\\^3\n* Platelet count \\>= 100,000\u002Fmm\\^3\n* Hemoglobin \\>= 8 g\u002FdL (prior transfusion is allowed if completed 2 weeks prior to screening and hemoglobin remains \\>= 8 g\u002FdL)\n* For patients with HCC with splenic sequestration: ANC \\>= 1000\u002Fmm\\^3\n* For patients with HCC with splenic sequestration: Platelets \\>= 70,000\n* Calculated clearance \\>= 60 mL\u002Fmin\u002F1.73 m\\^2. Actual body weight should be used for calculating creatinine clearance (e.g., using the Cockroft-Gault formula). For subjects with a Body Mass Index (BMI) \\> 30 kg\u002Fm\\^2, lean body weight should be used instead\n* Total bilirubin =\\\u003C 1.5 X upper limit of normal (ULN) (subjects with known Gilbert's hepatic function disease can have bilirubin of up to 2 X ULN)\n* Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) =\\\u003C 3 X ULN; or AST\u002FALT =\\\u003C 5 X ULN if patient has liver tumors\n* Prothrombin time (PT)\u002Finternational normalized ratio (INR) =\\\u003C 1.8 times upper limit of normal (unless patient is on anticoagulation)\n\nExclusion Criteria:\n\n* Patients who have had hypersensitivity to pentamidine or any excipients of AU409\n* Treatment with other anticancer therapies (including surgery, radiation therapy, chemotherapy, anti-angiogenic therapy, targeted therapy, or radiofrequency ablation therapy, etc.) or investigational therapy within 28 days prior to study entry (except for palliative radiation therapy that should be completed \\>= 14 days prior to study entry)\n* Hepatocellular carcinoma patients with a Child Pugh score \\>= B7\n* Patients with known central nervous system metastases which are untreated or symptomatic; patients with treated brain metastases (completed \\>= 30 days prior to screening) are allowed provided they are asymptomatic and are off steroids\n* Patient with a history of the following within 6 months prior to cycle 1 day 1: a myocardial infarction, severe\u002Funstable angina pectoris, coronary\u002Fperipheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia, cerebrovascular accident, transient ischemic attack, or seizure disorder. Atrial fibrillation is allowed if rate is controlled\n* Patients who have corrected QT (QTc) interval to \\> 470 msec (Fredericia's equation) on 2 out of 3 electrocardiogram (ECG)'s (if first ECG has QTc \\\u003C 470, no need to repeat, if first ECG has QTc \\> 470 repeat twice for a total of 3 ECG's)\n* Patients who are on therapeutic anticoagulation with warfarin; however, patients on therapeutic doses of with low molecular weight heparins or Factor Xa inhibitors are eligible\n* Patient with history of gastrointestinal surgery or malabsorptive conditions that may change the absorption of drugs and\u002For cause rapid transit (such as total gastrectomy, small bowel resection, etc.)\n* Patients who have known active hepatitis B. Patients with chronic hepatitis B who are on anti-viral therapy and have a hepatitis B viral load of =\\\u003C 500 IU\u002FmL are allowed on the study. Patients with chronic Hepatitis C are allowed\n* Patients who have active infection requiring treatment (except hepatitis B and C as noted above) including known human immunodeficiency virus (HIV) infection\n* Patients who have concurrent conditions resulting in immune compromise, including chronic treatment with corticosteroids or other immunosuppressive agents\n* Patients who have any other condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results\n* Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants\n* Patients who are on medications that are considered to be strong inducers or inhibitors of the cytochrome P450 isoenzymes should have such medications discontinued or replaced. Such medications should be avoided for one week prior to first dose of treatment and during the trial participation. If these medications are absolutely necessary for the patient and cannot be replaced, enrollment may still be considered on a case by case basis if it is in the patient's best interest and after discussion with the principal investigator (PI)","ALL","18 Years",{"count":19,"type":20},36,"ESTIMATED","INTERVENTIONAL",[23],"PHASE1","This phase I trial tests the safety, side effects, and best dose of a new intervention, AU409, in treating patients with primary liver cancers that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or advanced solid tumors that have spread to the liver (liver metastatic disease). AU409 may stop cancer from growing and spreading. This trial may help researchers determine if AU409 is safe and effective in treating patients with liver cancers and solid tumors with liver metastatic disease.",[26,27,28,29,30,31,32],"Advanced Cholangiocarcinoma","Advanced Hepatocellular Carcinoma","Advanced Malignant Solid Neoplasm","Metastatic Malignant Neoplasm in the Liver","Refractory Malignant Solid Neoplasm","Stage III Hepatocellular Carcinoma AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8","RECRUITING","2026-05-29",{"date":36,"type":37},"2026-06-01","ACTUAL",{"date":39,"type":37},"2023-03-29",{"date":41,"type":20},"2028-03-29",{"name":43,"class":44},"University of Southern California","OTHER",2,{"id":47,"slug":48,"hasResults":11,"nctId":49,"briefTitle":50,"officialTitle":51,"acronym":4,"eligibilityCriteria":52,"healthyVolunteers":11,"sex":16,"minAge":53,"maxAge":54,"enrollmentInfo":55,"targetDuration":4,"studyType":21,"phases":57,"briefSummary":59,"conditions":60,"keywords":82,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":91,"lastUpdatePostDateStruct":92,"startDateStruct":94,"completionDateStruct":96,"leadSponsor":98,"locationsCount":100},"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":56,"type":20},90,[23,58],"PHASE2","The phase I portion of this study is designed for children or adolescents and young adults (AYA) with a diagnosis of a solid tumor that has recurred (come back after treatment) or is refractory (never completely went away). The trial will test 2 combinations of therapy and participants will be randomly assigned to either Arm A or Arm B. The purpose of the phase I study is to determine the highest tolerable doses of the combinations of treatment given in each Arm.\n\nIn Arm A, children and AYAs with recurrent or refractory solid tumors will receive 2 medications called Onivyde and talazoparib. Onivyde works by damaging the DNA of the cancer cell and talazoparib works by blocking the repair of the DNA once the cancer cell is damaged. By damaging the tumor DNA and blocking the repair, the cancer cells may die. In Arm B, children and AYAs with recurrent or refractory solid tumors will receive 2 medications called Onivyde and temozolomide. Both of these medications work by damaging the DNA of the cancer call which may cause the tumor(s) to die.\n\nOnce the highest doses are reached in Arm A and Arm B, then \"expansion Arms\" will open. An expansion arm treats more children and AYAs with recurrent or refractory solid tumors at the highest doses achieved in the phase I study. The goal of the expansion arms is to see if the tumors go away in children and AYAs with recurrent or refractory solid tumors. There will be 3 \"expansion Arms\". In Arm A1, children and AYAs with recurrent or refractory solid tumors (excluding Ewing sarcoma) will receive Onivyde and talazoparib. In Arm A2, children and AYAs with recurrent or refractory solid tumors, whose tumors have a problem with repairing DNA (identified by their doctor), will receive Onivyde and talazoparib. In Arm B1, children and AYAs with recurrent or refractory solid tumors (excluding Ewing sarcoma) will receive Onivyde and temozolomide.\n\nOnce the highest doses of medications used in Arm A and Arm B are determined, then a phase II study will open for children or young adults with Ewing sarcoma that has recurred or is refractory following treatment received after the initial diagnosis. The trial will test the same 2 combinations of therapy in Arm A and Arm B. In the phase II, a participant with Ewing sarcoma will be randomly assigned to receive the treatment given on either Arm A or Arm B.",[61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,30,76,77,78,79,80,81],"Recurrent Solid Tumor","Recurrent Ewing Sarcoma","Recurrent Hepatoblastoma","Recurrent Malignant Germ Cell Tumor","Recurrent Malignant Solid Neoplasm","Recurrent Neuroblastoma","Recurrent Osteosarcoma","Recurrent Peripheral Primitive Neuroectodermal Tumor","Recurrent Rhabdoid Tumor","Recurrent Rhabdomyosarcoma","Recurrent Soft Tissue Sarcoma","Recurrent Wilms Tumor","Refractory Ewing Sarcoma","Refractory Hepatoblastoma","Refractory Malignant Germ Cell Tumor","Refractory Neuroblastoma","Refractory Osteosarcoma","Refractory Peripheral Primitive Neuroectodermal Tumor","Refractory Rhabdoid Tumor","Refractory Rhabdomyosarcoma","Refractory Soft Tissue Sarcoma",[83,84,85,86,87,88,89,90],"Pediatric Cancer","Childhood Cancer","Ewing Sarcoma","PARP inhibitor","Solid tumor","Irinotecan","Onivyde","Talazoparib","2026-05-18",{"date":93,"type":37},"2026-05-19",{"date":95,"type":37},"2021-06-09",{"date":97,"type":20},"2026-12-31",{"name":99,"class":44},"St. Jude Children's Research Hospital",10,{"id":102,"slug":103,"hasResults":11,"nctId":104,"briefTitle":105,"officialTitle":106,"acronym":4,"eligibilityCriteria":107,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":108,"targetDuration":4,"studyType":21,"phases":110,"briefSummary":111,"conditions":112,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":116,"lastUpdatePostDateStruct":117,"startDateStruct":119,"completionDateStruct":121,"leadSponsor":123,"locationsCount":126},"100533263","phase-1-studying-tak-243-in-patients-with-advanced-cancer-100533263","NCT06223542","Studying TAK-243 in Patients With Advanced Cancer","A Phase I Study to Investigate the Safety of the Ubiquitin Activating Enzyme Inhibitor TAK-243 in Adult Solid Tumor and Lymphoma Patients","Inclusion Criteria:\n\n* Patients with histologically documented advanced or metastatic solid tumors with relapsed or refractory disease who have received standard-of-care or approved therapies known to confer clinical benefit, or patients with aggressive lymphomas who have received ≥ 2 prior lines of lymphoma-directed therapy and who do not have remaining effective treatment options (including transplant). Additionally, patients with indolent lymphomas must meet criteria for treatment.\n* Patients must have measurable or evaluable disease\n* Age \\>= 18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2\n* Hemoglobin \\>= 9 g\u002FdL (patients may be transfused to achieve this value; elevated indirect bilirubin due to post-transfusion hemolysis is allowed)\n* Absolute neutrophil count \\>= 1,000\u002FmcL\n* Platelets \\>= 75,000\u002FmcL\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 3 x institutional ULN OR =\\\u003C 5 x institutional upper limit of normal for patients with liver metastases at baseline\n* Creatinine =\\\u003C 1.5 x institutional ULN OR creatinine clearance \\>= 60 mL\u002Fmin\u002F1.73 m\\^2 by Cockcroft-Gault\n* Any prior therapy must have been completed \\>= 4 weeks, or \\>= 5 half-lives of the prior agent (whichever is shorter) prior to enrollment on protocol. Prior definitive radiation should have been completed \\>= 4 weeks prior to enrollment; prior palliative radiation should have been completed \\>= 2 weeks prior to enrollment. Patients must be \\>= 2 weeks since any investigational agent administered as part of a Phase 0 study (where a sub-therapeutic dose of drug is administered) and should have recovered to grade 1 or baseline from any toxicities\n* Female patients who:\n\n  * Are postmenopausal (age-related amenorrhea \\>= 12 consecutive months or follicle-stimulating hormone \\> 40 mIU\u002FmL), for at least 1 year before the screening visit, OR\n  * Are surgically sterile (i.e., who had undergone hysterectomy or bilateral oophorectomy), OR\n\nIf they are of childbearing potential:\n\n* Agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug (female and male condoms should not be used together), or\n* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \\[e.g., calendar, ovulation, symptothermal, postovulation methods\\] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)\n\n  * Male patients, even if surgically sterilized (i.e., status postvasectomy), who:\n* Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug (female and male condoms should not be used together), or\n* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \\[eg, calendar, ovulation, symptothermal, postovulation methods for the female partner\\] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)\n\n  * The effects of TAK-243 on the developing human fetus are unknown. For this reason and because ubiquitin-activating enzyme inhibitors are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of TAK-243 administration\n  * Ability to understand and the willingness to sign a written informed consent document\n  * Willingness to provide blood for research purposes\n  * For expansion phase patients, willingness to undergo 2 core needle biopsy procedures for research purposes if there is a lesion or lesions amenable to repeat biopsy\n  * Patients on anticoagulation therapy are eligible for this study in the absence of anticipated drug-drug interactions (DDI) between the anticoagulation agent and TAK-243. If DDI are anticipated and another anticoagulation agent that is compatible with TAK-243 exists, the patient will be transitioned to this alternative, TAK-243-compatible anticoagulation agent\n\nExclusion Criteria:\n\n* Patients who are receiving any other investigational agents\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Life-threatening illness unrelated to cancer\n* Patients with uncontrolled coagulopathy or bleeding disorder\n* Known hepatic cirrhosis or severe pre-existing hepatic impairment\n* Known cardiopulmonary disease defined as:\n\n  * Unstable angina pectoris;\n  * Congestive heart failure (New York Heart Association \\[NYHA\\] class III or IV);\n  * Myocardial infarction (MI) within 6 months prior to first dose (patients who had ischemic heart disease such as a \\[acute coronary syndrome (ACS)\\], MI, and\u002For revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll);\n  * Cardiomyopathy\n* Clinically significant arrhythmia:\n\n  * History of polymorphic ventricular fibrillation or torsade de pointes,\n  * Permanent atrial fibrillation (a fib), defined as continuous a fib for \\>= 6 months,\n  * Persistent a fib, defined as sustained a fib lasting \\> 7 days and\u002For requiring cardioversion in the 4 weeks before screening,\n  * Grade 3 a fib defined as symptomatic and incompletely controlled medically, or controlled with device (e.g., pacemaker) or ablation, and\n  * Patients with paroxysmal a fib or \\\u003C grade 3 a fib for period of at least 6 months are permitted to enroll provided that their rate is controlled on a stable regimen\n* Prolonged rate corrected QT (QTc) interval \\>= 470 m\u002Fsec, calculated according to institutional guidelines\n* Uncontrolled high blood pressure (i.e., systolic blood pressure \\> 180 mm Hg, diastolic blood pressure \\> 95 mm Hg)\n* Known moderate to severe chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis\n* Major surgery within 14 days before the first dose of any study drug\n* Female patients who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s)\n* Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s)\n* Patients with known brain metastases or carcinomatous meningitis are excluded from this clinical trial, with the exception of patients whose brain metastatic disease status has remained stable for \\>= 1 month after treatment of the brain metastases. Patients on anti-seizure medications may be enrolled at the discretion of the principal investigator\n* TAK-243 is primarily metabolized by CYP3A4\u002F5. Therefore, the concomitant use of strong inhibitors of CYP3A4\u002F5 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir) and strong inducers of CYP3A4\u002F5 (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) is not permitted from 14 days prior to enrollment until the end of the study\n\n  * TAK-243 is a substrate for both organic anion transporting polypeptides (OATP) in human hepatocytes and the drug efflux transporter BCRP (ABCG2). Therefore, concomitant use of drugs that are strong inhibitors of BCRP or OATP is not permitted from 14 days prior to enrollment until the end of the study\n  * Other medications that are prohibited while on TAK-243 treatment include herbal medications\u002Fpreparations (except for vitamins). Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of\n  * As part of the enrollment\u002Finformed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product\n* Patients undergoing vaccination with live vaccines and live attenuated vaccines in the 30 days prior to receiving TAK-243, during the study, and for 100 days after the last dose of study drug. Inactivated vaccines are permitted\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAK-243\n* Patients with evidence of chronic hepatitis B virus (HBV) infection who are currently on treatment are eligible if they have an undetectable HBV viral load\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Known human immunodeficiency virus (HIV)-positive patients who meet the following criteria will be considered eligible:\n\n  * CD4 count \\> 350 cells\u002Fmm\\^3\n  * Undetectable viral load for 6 months prior to enrollment\n  * Maintained on modern therapeutic regimens utilizing non-CYP-interactive agents\n  * No history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections\n* Pregnant and lactating\u002Fbreast-feeding women are excluded from this study because TAK-243 is a UAE-inhibiting agent with the potential for teratogenic or abortifacient effects and there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TAK-243",{"count":109,"type":20},95,[23],"This phase I trial studies the side effects and best dose of ubiquitin-activating enzyme (UAE) inhibitor TAK-243 (TAK-243) in treating patients with a solid tumor that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic) and in patients with lymphoma. TAK-243 is a drug that binds to and inhibits the ubiquitin-activating enzyme, an enzyme that is more active on cancer cells than healthy cells, inhibiting tumor cell proliferation and survival.",[113,28,114,115,65,30],"Advanced Lymphoma","Indolent Non-Hodgkin Lymphoma","Metastatic Malignant Solid Neoplasm","2026-05-12",{"date":118,"type":37},"2026-05-13",{"date":120,"type":37},"2025-03-24",{"date":122,"type":20},"2027-04-15",{"name":124,"class":125},"National Cancer Institute (NCI)","NIH",1,{"id":128,"slug":129,"hasResults":11,"nctId":130,"briefTitle":131,"officialTitle":132,"acronym":4,"eligibilityCriteria":133,"healthyVolunteers":11,"sex":16,"minAge":134,"maxAge":135,"enrollmentInfo":136,"targetDuration":4,"studyType":21,"phases":138,"briefSummary":139,"conditions":140,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":148,"lastUpdatePostDateStruct":149,"startDateStruct":151,"completionDateStruct":153,"leadSponsor":155,"locationsCount":158},"100563756","phase-1-testing-the-addition-of-an-anti-cancer-drug-dt2216-to-the-usual-chemotherapy-treatment-for-relapsed-or-refractory-solid-tumors-and-fibrolamellar-carcinoma-100563756","NCT06620302","Testing the Addition of an Anti-cancer Drug, DT2216, to the Usual Chemotherapy Treatment for Relapsed or Refractory Solid Tumors and Fibrolamellar Carcinoma","DT2216 in Combination With Irinotecan for Children, Adolescents and Young Adults With Relapsed or Refractory Solid Tumors: A Phase I Study With Phase II Feasibility Cohort for Fibrolamellar Carcinoma","Inclusion Criteria:\n\n* PHASE 1: Patients between ≥ 1 year and ≤ 21 years of age at the time of study enrollment\n* PHASE 2: Patients between ≥ 1 year and ≤ 39 years of age at the time of study enrollment\n* PHASE 1: Patients with recurrent\u002Frefractory solid tumors excluding primary central nervous system tumors\n* PHASE 2: Patients with (FLC), which must include genomic confirmation of the DNAJB1:PRKACA fusion performed at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory\n* PHASE 1: Patients must have either measurable or evaluable disease\n* PHASE 2: Patients must have measurable disease\n* PHASE 1: Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life\n* PHASE 2: Patients must have FLC which is recurrent\u002Frefractory to at least one line of prior systemic therapy\n* Patients with FLC that is unresectable at initial diagnosis but is not recurrent\u002Frefractory to at least one prior line of systemic therapy nor metastatic are NOT eligible for either phase 1 or phase 2\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 ≤ 16 years of age\n* Patients must have fully recovered (grade \\\u003C 2) 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, eg, blood count criteria, the patient is considered to have recovered adequately\n\n  * Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See Developmental Therapeutics (DVL) homepage on the Children's Oncology Group (COG) members site for commercial and investigational agent classifications. 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    * Solid tumor patients: ≥ 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). Please refer to the table of myelosuppressive\u002Fanticancer agents on the COG website\n  * Anti-cancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count \\[ANC\\] counts): ≥ 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. 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  * 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 ≤ 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 (eg, 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 of any type of cellular therapy (eg, modified T cells, natural killer \\[NK\\] cells, dendritic cells, etc.)\n  * Radiotherapy (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 (eg, radiolabeled antibody, lobenguane I-131 \\[131I-MIBG\\]): ≥ 42 days after systemically administered radiopharmaceutical therapy\n  * Patients must not have received prior Bcl-xL specific therapy (e.g. navitoclax, DT2216). Prior therapy with irinotecan or other topoisomerase 1 inhibitors and\u002For other BH3 mimetics which are not Bcl-xL selective (e.g. venetoclax) are acceptable\n* For patients with solid tumors without known bone marrow involvement: Peripheral absolute neutrophil count (ANC) ≥ 1000\u002FµL\n* For patients with solid tumors without known bone marrow involvement: Platelet count ≥ 100,000\u002FµL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)\n* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the 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 must be evaluable for hematologic toxicity\n* A creatinine based on age\u002Fgender as follows:\n\n  * 1 to \\\u003C 2 years: Maximum serum creatinine (mg\u002FdL) 0.6 (male), 0.6 (female)\n  * 2 to \\\u003C 6 years: Maximum serum creatinine (mg\u002FdL) 0.8 (male), 0.8 (female)\n  * 6 to \\\u003C 10 years: Maximum serum creatinine (mg\u002FdL) 1 (male), 1 (female)\n  * 10 to \\\u003C 13 years: Maximum serum creatinine (mg\u002FdL) 1.2 (male), 1.2 (female)\n  * 13 to \\\u003C 16 years: Maximum serum creatinine (mg\u002FdL) 1.5 (male), 1.4 (female)\n  * 16 to ≤ 39 years: Maximum serum creatinine (mg\u002FdL) 1.7 (male), 1.4 (female)\n\n    * OR a 24 hour urine creatinine clearance ≥ 70 mL\u002Fmin\u002F1.73 m\\^2\n    * OR a glomerular filtration rate (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). Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility\n* Patients with solid tumors: Bilirubin (sum of conjugated + unconjugated or total) ≤ 1.5 x upper limit of normal (ULN) for age\n* Patients with solid tumors: Alanine aminotransferase (ALT) ≤ 3 x ULN, unless attributed to tumor involvement then ALT ≤ 5 x ULN\n\n  * Note: For the purposes of this study the ULN for ALT is defined as 45 U\u002FL\n* Patients with solid tumors: Aspartate aminotransferase (AST) ≤ 3 x ULN, unless attributed to tumor involvement then AST ≤ 5 x ULN\n\n  * Note: For the purposes of this study the ULN for AST is defined as 50 U\u002FL\n* Patients with solid tumors: Albumin ≥ 2 g\u002FdL\n* Patients with solid tumors: International normalized ratio (INR) ≤ 2.5\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. If needed, evaluate use of enzyme-inducing anticonvulsants\n* Nervous system disorders (Common Terminology Criteria for Adverse Events \\[CTCAE\\] version \\[v\\]5) resulting from prior therapy must be ≤ grade 2, with the exception of decreased tendon reflex (DTR). Patient with any grade of tendon reflex decrease are eligible\n\nExclusion Criteria:\n\n* Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal\u002Fhuman studies, OR 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 (eg, male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control. Patients who could become pregnant should use highly effective contraception during therapy and for 6 months after the last irinotecan dose or 120 days after the last dose of DT2216, whichever is longer. Patients with partners who could become pregnant should use condoms during therapy and for 3 months after the last dose irinotecan or 120 days after the last dose of DT2216, whichever is longer\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 have received drugs that are strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment are not eligible\n* Patients with lymphoma are excluded\n* Patients who have an uncontrolled infection are not eligible\n* Patients with grade ≥ 2 diarrhea at baseline 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\n* Dedicated central nervous system (CNS) imaging is not required but patients with current active CNS metastasis whether symptomatic or discovered incidentally without clinical symptoms, are not eligible\n* Patients with grade \\> 2 corrected QT interval (i.e. electrocardiogram \\[EKG\\] showing corrected QT interval \\[QTc\\] \\> 480 ms) at baseline are not eligible\n* Surgical procedure\n\n  * Central line placement, open or core needle biopsy of sites other than liver: \\\u003C 2 days prior to enrollment.\n  * Open or laparoscopic biopsies or core needle biopsies of liver \\\u003C 7 days prior to enrollment.\n  * All other surgeries \\\u003C 14 days prior to enrollment","1 Year","39 Years",{"count":137,"type":20},81,[23,58],"This phase I\u002FII trial tests the safety, side effects and best dose of DT2216 in combination with irinotecan and how well it works in treating children, adolescents and young adults with solid tumors and fibrolamellar cancer that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). DT2216 is an anti-apoptotic protein B-cell lymphoma-extra large targeted protein degrader. It may stop the growth of tumor cells by blocking Bcl-xL, a protein needed for tumor cell survival. Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid repair and may kill tumor cells. Giving DT2216 in combination with irinotecan may be safe, tolerable, and\u002For effective in treating children, adolescents and young adults with relapsed or refractory solid tumors or fibrolamellar cancer.",[141,142,143,144,65,145,146,147,30],"Childhood Fibrolamellar Carcinoma","Recurrent Childhood Fibrolamellar Carcinoma","Recurrent Childhood Malignant Solid Neoplasm","Recurrent Fibrolamellar Carcinoma","Refractory Childhood Fibrolamellar Carcinoma","Refractory Childhood Malignant Solid Neoplasm","Refractory Fibrolamellar Carcinoma","2026-05-01",{"date":150,"type":37},"2026-05-05",{"date":152,"type":37},"2025-06-12",{"date":154,"type":20},"2031-12-30",{"name":156,"class":157},"Children's Oncology Group","NETWORK",21,{"id":160,"slug":161,"hasResults":11,"nctId":162,"briefTitle":163,"officialTitle":164,"acronym":4,"eligibilityCriteria":165,"healthyVolunteers":11,"sex":16,"minAge":53,"maxAge":166,"enrollmentInfo":167,"targetDuration":4,"studyType":21,"phases":169,"briefSummary":170,"conditions":171,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":148,"lastUpdatePostDateStruct":180,"startDateStruct":181,"completionDateStruct":183,"leadSponsor":184,"locationsCount":185},"100429351","phase-1-cbl0137-for-the-treatment-of-relapsed-or-refractory-solid-tumors-including-cns-tumors-and-lymphoma-100429351","NCT04870944","CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma","A Phase 1\u002F2 Trial of CBL0137 (NSC# 825802) in Patients With Relapsed or Refractory Solid Tumors Including CNS Tumors and Lymphoma","Inclusion Criteria:\n\n* Parts A and B: Patients must be \\>= 12 months and =\\\u003C 21 years of age at the time of study enrollment\n* Patients must have had histologic verification of malignancy at original diagnosis or relapse, except in patients with diffuse intrinsic brain stem tumors, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers, including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)\n\n  * Part A: Patients with relapsed or refractory solid tumors or lymphoma, including patients with CNS tumors or known CNS metastases (including untreated or progressive) are eligible\n  * Part B: Patients with progressive or recurrent DIPG (diagnosed by biopsy or imaging characteristics) and other H3 K27-altered DMG previously treated with radiation therapy\n* Part A: Patients must have either measurable or evaluable disease\n* Part B: Patients must have measurable disease\n* Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life\n* Patients must have a performance status corresponding to Easter 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. Patients must have a Karnofsky or Lansky score \\>= 50%\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  * Anti-cancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count \\[ANC\\] counts): \\>= 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. Patients with CNS tumors receiving corticosteroids must have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment\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: \\>= 42 days after the completion 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: \\>= 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, I-131 metaiodobenzylguanidine \\[131I MIBG\\]): \\>= 42 days after systemically administered radiopharmaceutical therapy\n  * Patients must not have received prior exposure to CBL0137\n* For patients with solid tumors without known bone marrow involvement:\n\n  * Peripheral absolute neutrophil count (ANC) \\>= 1000\u002FuL (performed within 7 days prior to enrollment unless otherwise indicated)\n  * Patients with known bone marrow metastatic disease will be eligible for study provided they meet the 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 must be evaluable for hematologic toxicity\n* For patients with solid tumors without known bone marrow involvement:\n\n  * Platelet count \\>= 100,000\u002FuL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (performed within 7 days prior to enrollment unless otherwise indicated)\n  * Patients with known bone marrow metastatic disease will be eligible for study provided they meet the 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 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\u002Fsex as follows (performed within 7 days prior to enrollment unless otherwise indicated):\n\n  * Age: Maximum serum creatinine (mg\u002FdL)\n  * 1 to \\\u003C 2 years: 0.6 (male); 0.6 (female)\n  * 2 to \\\u003C 6 years: 0.8 (male); 0.8 (female)\n  * 6 to \\\u003C 10 years: 1 (male); 1 (female)\n  * 10 to \\\u003C 13 years: 1.2 (male); 1.2 (female)\n  * 13 to \\\u003C 16 years: 1.5 (male); 1.4 (female)\n  * \\>= 16 years: 1.7 (male); 1.4 (female)\n* Patients with solid tumors:\n\n  * Bilirubin (sum of conjugated + unconjugated or total) =\\\u003C 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment unless otherwise indicated)\n* Patients with solid tumors:\n\n  * Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \\[ALT\\]) =\\\u003C 135 U\u002FL. For the purpose of this study, the ULN for SGPT is 45 U\u002FL (performed within 7 days prior to enrollment unless otherwise indicated)\n* Shortening fraction of \\>= 27% by echocardiogram (performed within 7 days prior to enrollment unless otherwise indicated) or\n* Ejection fraction of \\>= 50% by gated radionuclide study (performed within 7 days prior to enrollment unless otherwise indicated)\n* Corrected QT (QTC) \\\u003C 480 msec (performed within 7 days prior to enrollment unless otherwise indicated)\n* Patients with seizure disorder may be enrolled if seizures well controlled without the use of enzyme-inducing anti-convulsant agents. Well controlled is defined 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 therapy must be =\\\u003C grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible\n* Patients have consented to receive a central venous catheter prior to the administration of CBL0137. A central line is required for CBL0137 administration\n\nExclusion Criteria:\n\n* Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal\u002Fhuman studies, OR 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 (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)\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 drugs that are strong inducers or inhibitors of CYP3A4, CYP2B6 (e.g., carbamazepine) and CYP1A2 (e.g., ciprofloxacin, enoxacin, fluvoxamine, smoking) are not eligible. These agents are to be avoided for 7 days prior to the start of CBL0137 and for the duration of the protocol therapy. Sensitive substrates of CYP2D6 (e.g., atomoxetine, desipramine, dextromethorphan, eliglustat, nebivolol, nortriptyline, perphenazine, tolterodine, R-venlafaxine) should also be avoided for the duration protocol therapy\n* Patients who are receiving drugs associated with a known risk of Torsades de Pointes (TdP) are not eligible. Drugs associated with known risk of Torsades de Pointes (TdP) are to be avoided for 7 days prior to the start of CBL0137 and for duration of the protocol therapy\n* Patients with known peripheral vascular disease are excluded\n* Patients with a history of pro-thrombotic disorder are not eligible\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","21 Years",{"count":168,"type":20},63,[23,58],"This phase I\u002FII trial evaluates the best dose, side effects and possible benefit of CBL0137 in treating patients with solid tumors, including central nervous system (CNS) tumors or lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Drugs, such as CBL0137, block signals passed from one molecule to another inside a cell. Blocking these signals can affect many functions of the cell, including cell division and cell death, and may kill cancer cells.",[172,173,174,175,176,65,177,178,30,179],"Diffuse Midline Glioma, H3 K27-Altered","Metastatic Malignant Neoplasm in the Central Nervous System","Recurrent Diffuse Intrinsic Pontine Glioma","Recurrent Diffuse Midline Glioma, H3 K27-Altered","Recurrent Lymphoma","Recurrent Primary Malignant Central Nervous System Neoplasm","Refractory Lymphoma","Refractory Primary Malignant Central Nervous System Neoplasm",{"date":150,"type":37},{"date":182,"type":37},"2022-01-28",{"date":97,"type":20},{"name":156,"class":157},35,{"id":187,"slug":188,"hasResults":11,"nctId":189,"briefTitle":190,"officialTitle":191,"acronym":4,"eligibilityCriteria":192,"healthyVolunteers":11,"sex":16,"minAge":53,"maxAge":54,"enrollmentInfo":193,"targetDuration":4,"studyType":21,"phases":195,"briefSummary":196,"conditions":197,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":148,"lastUpdatePostDateStruct":212,"startDateStruct":213,"completionDateStruct":215,"leadSponsor":217,"locationsCount":158},"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":194,"type":20},147,[23,58],"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.",[198,199,200,201,202,203,204,62,63,205,65,206,67,207,73,74,208,30,209,77,210,211],"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","Wilms Tumor",{"date":150,"type":37},{"date":214,"type":37},"2021-11-08",{"date":216,"type":20},"2028-06-30",{"name":156,"class":157},{"id":219,"slug":220,"hasResults":11,"nctId":221,"briefTitle":222,"officialTitle":223,"acronym":4,"eligibilityCriteria":224,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":225,"targetDuration":4,"studyType":21,"phases":227,"briefSummary":228,"conditions":229,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":237,"lastUpdatePostDateStruct":238,"startDateStruct":240,"completionDateStruct":242,"leadSponsor":244,"locationsCount":245},"100443405","phase-1-testing-a-new-anti-cancer-drug-combination-entinostat-and-zen003694-for-advanced-and-refractory-solid-tumors-100443405","NCT05053971","Testing A New Anti-cancer Drug Combination, Entinostat and ZEN003694, for Advanced and Refractory Solid Tumors","Phase Ib\u002FII Study of ZEN003694 and Entinostat in Advanced and Refractory Solid Tumors","Inclusion Criteria:\n\n* Patients must have a) advanced or refractory solid tumor and must meet standard requirements for treatment\n* For patients in Phase 2: Patients must have locally advanced, unresectable OR metastatic pancreatic cancer refractory to standard therapy\n* For patients with solid tumors, they must have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria\n* For patients with solid tumors, they must have received at least one standard of care regimen for metastatic disease\n* Age \\>= 18 years. Because no dosing or adverse event data are currently available on the use of ZEN003694, alone or in combination with entinostat, in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 1 (Karnofsky \\>= 70%)\n* Hemoglobin \\>= 9.0 g\u002FdL (measured within 14 days prior to administration of study treatment)\n* Absolute neutrophil count (ANC) \\>= 1,500\u002FmcL (measured within 14 days prior to administration of study treatment)\n* Platelets \\>= 100,000\u002FmcL (measured within 14 days prior to administration of study treatment)\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (ULN) (measured within 14 days prior to administration of study treatment)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 2.5 x institutional ULN (measured within 14 days prior to administration of study treatment)\n* Glomerular filtration rate (GFR) \\>= 60 mL\u002Fmin\u002F1.73 m\\^2 for patients with creatinine levels above institutional normal (measured within 14 days prior to administration of study treatment)\n* Prothrombin time (PT)\u002Finternational normalized ratio (INR) and partial thromboplastin time (PTT) test \\\u003C 1.5 x ULN (measured within 14 days prior to administration of study treatment)\n* Albumin \\> 2.5 g\u002FdL (measured within 14 days prior to administration of study treatment)\n* Patients with treated brain metastases are eligible if follow-up brain imaging at least 4 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Patients should be New York Heart Association Functional Classification of class 2B or better\n* Patients must be able to swallow and retain orally administered medication\n* Women of childbearing potential must have a negative pregnancy test within 7 days of starting treatment\n* The effects of entinostat and ZEN003694 on the developing human fetus are unknown. For this reason and because histone deacetylase inhibitor (HDACi) and BET inhibitor (BETi) agents are known to be teratogenic, women of child-bearing potential and their male partner must agree to use contraception from the time of the screening pregnancy test, continuing for the duration of study participation, and for 3 months after completing the study treatment\n* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and\u002For family member available will also be eligible\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n\nExclusion Criteria:\n\n* Patients who have had any anti-cancer therapy within 30 days (or 5 half-lives, whichever is shorter) prior to the first dose of the investigational products\n* Patients who have received radiation therapy within 21 days prior to the first dose of the investigational products\n* Patients who have a diagnosis of NK cell lymphoma\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia, or stable chronic grade 2 toxicities that do not overlap with presumed toxicities of entinostat or ZEN003694\n* Patients who are receiving any other investigational agents\n* Patients with known untreated or symptomatic brain or leptomeningeal metastases are excluded. Patients with previously treated CNS metastasis may be included provided that they have stable CNS disease for at least 4 weeks (confirmed by imaging) without symptoms and are off corticosteroids (above physiologic dose) for that indication\n* Patients with significant malabsorption or nausea and vomiting that would interfere with oral therapies\n* Patients with bleeding diathesis or clinically significant bleeding within the prior 6 months\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat (e.g. medications that have a benzamide structure (tiapride, remoxipride, clebopride) or ZEN003694\n* Patients receiving any medications or substances that are strong inhibitors or strong inducers of CYP3A4 or substrates of CYP1A2 with narrow therapeutic windows are ineligible. Strong inhibitors or inducers of CYP3A4 and substrates of CYP1A2 must be discontinued at least 7 days prior to the first dose of ZEN003694. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment\u002Finformed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product\n* Patients with uncontrolled intercurrent illness\n* Pregnant women are excluded from this study because entinostat is an HDACi and ZEN003694 is a BETi with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with entinostat or ZEN003694, breastfeeding should be discontinued throughout the treatment period and for at least 28 days following the last dose of study treatment if the mother is treated with entinostat or ZEN003694\n* Patients with any of the following cardiac criteria:\n\n  * Patients with a corrected QT interval calculated by the Fridericia formula (QTcF) \\> 450 msec by electrocardiogram (ECG).\n  * Concomitant use of any agent known to cause corrected QT interval (QTc) prolongation.\n  * Clinically significant conduction abnormalities or arrhythmias.\n  * Presence of a cardiac pacemaker or defibrillator with a paced ventricular rhythm limiting ECG analysis.\n  * History or evidence of current \\>= Class II congestive heart failure as defined by New York Heart Association (NYHA).\n  * History of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 6 months. Subjects with a history of stent placement requiring ongoing antithrombotic therapy (e.g. clopidogrel, prasugrel) will not be permitted to enroll. Clinically significant cardiomegaly, ventricular hypertrophy, or cardiomyopathy\n* Use of oral Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed\n* Patients with radiation to \\> 25% of the bone marrow\n* Patients who have had a bone-targeted radionuclide within 6 weeks of the first dose of ZEN003694\n* Patients who have previously received ZEN003694 or who have been treated with an HDAC inhibitor or investigational BET inhibitor\n* Major surgery other than diagnostic surgery, dental surgery or stenting within 4 weeks prior to the first dose of ZEN003694",{"count":226,"type":20},49,[23,58],"This phase I\u002FII trial tests the safety, side effects, and best dose of entinostat and ZEN003694 in treating patients with solid tumors that have spread to other places in the body (advanced) or does not respond to treatment (refractory). Entinostat is in a class of drugs called histone deacetylase (HDAC) inhibitors. It may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. ZEN003694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that over produce BET protein. This trial aims to test the safety of combination therapy with entinostat and ZEN003694 in treating patients with advanced or refractory solid tumors.",[28,230,231,30,232,233,234,235,236],"Locally Advanced Pancreatic Carcinoma","Metastatic Pancreatic Carcinoma","Refractory Pancreatic Carcinoma","Stage II Pancreatic Cancer AJCC v8","Stage III Pancreatic Cancer AJCC v8","Stage IV Pancreatic Cancer AJCC v8","Unresectable Pancreatic Carcinoma","2026-04-09",{"date":239,"type":37},"2026-04-13",{"date":241,"type":37},"2022-11-16",{"date":243,"type":20},"2026-07-01",{"name":124,"class":125},3,{"id":247,"slug":248,"hasResults":11,"nctId":249,"briefTitle":250,"officialTitle":251,"acronym":4,"eligibilityCriteria":252,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":253,"targetDuration":4,"studyType":21,"phases":255,"briefSummary":256,"conditions":257,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":259,"lastUpdatePostDateStruct":260,"startDateStruct":262,"completionDateStruct":264,"leadSponsor":266,"locationsCount":126},"100586102","phase-1-mti-301-for-the-treatment-of-metastatic-or-unresectable-and-refractory-solid-cancers-100586102","NCT06911008","MTI-301 for the Treatment of Metastatic or Unresectable and Refractory Solid Cancers","Phase I Trial of SCD I: A First in Human Dose Regimen-Finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Activity of MTI-301 in Patients With Advanced Malignancy","Inclusion Criteria:\n\n* Age ≥ 18 years.\n* Histologically or cytologically confirmed solid tumor (cancer) that is metastatic or unresectable and who are refractory to or intolerant of existing, standard-of-care therapy(ies), known to provide clinical benefit for their condition.\n* Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria or evaluable disease.\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2.\n* Hemoglobin ≥ 9.0 g\u002FdL (obtained ≤ 28 days prior to registration).\n* Absolute neutrophil count (ANC) ≥ 1500\u002Fmm\\^3 (obtained ≤ 28 days prior to registration).\n* Platelet count ≥ 100,000\u002Fmm\\^3 (obtained ≤ 28 days prior to registration).\n* Total bilirubin ≤ 1.5 x upper limit normal (ULN). Patients with Gilbert's syndrome: Total bilirubin ≤ 3 x ULN (obtained ≤ 28 days prior to registration).\n* Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 28 days prior to registration).\n* Prothrombin time (PT)\u002Finternational normalized ratio (INR)\u002Factivated partial thromboplastin time (aPTT) =\\\u003C 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy as determined by treating investigator (obtained ≤ 28 days prior to registration).\n* Calculated creatinine clearance ≥ 60 mL\u002Fmin using the Cockcroft-Gault formula (obtained ≤ 28 days prior to registration).\n* Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only.\n\n  * NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.\n* Provide written informed consent.\n* Ability to complete questionnaire(s) by themselves or with assistance.\n* Willingness to provide mandatory blood specimens for correlative research.\n* Willingness to provide mandatory tissue specimens for correlative research.\n* Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).\n\nExclusion Criteria:\n\n* Any of the following because this study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown:\n\n  * Pregnant persons\n  * Nursing persons\n  * Persons who are of childbearing potential who are unwilling to employ adequate contraception.\n  * NOTE: For the purpose of this guidance, methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include:\n\n    * Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation \\[Hormonal contraception may be susceptible to interaction with the investigational medicinal product (IMP), which may reduce the efficacy of the contraception method.\\]:\n\n      * Oral\n      * Intravaginal\n      * Transdermal\n    * Progestogen-only hormonal contraception associated with inhibition of ovulation (Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the efficacy of the contraception method.):\n\n      * Oral\n      * Injectable\n      * Implantable (Contraception methods that in the context of this guidance are considered to have low user dependency.)\n    * Intrauterine device (IUD) (Contraception methods that in the context of this guidance are considered to have low user dependency)\n    * Intrauterine hormone-releasing system (IUS) (Contraception methods that in the context of this guidance are considered to have low user dependency.)\n    * Bilateral tubal occlusion (Contraception methods that in the context of this guidance are considered to have low user dependency.)\n    * Vasectomised partner \\[Contraception methods that in the context of this guidance are considered to have low user dependency. Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the women of childbearing potential (WOCBP) trial participant and that the vasectomised partner has received medical assessment of the surgical success.\\]\n    * Sexual abstinence (In the context of this guidance sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.).\n* Any of the following prior therapies:\n\n  * Major surgery ≤ 3 weeks prior to registration\n  * Chemotherapy ≤ 2 weeks prior to registration\n  * Immunotherapy ≤ 3 weeks prior to registration\n  * Radiation ≤ 2 weeks prior to registration.\n* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.\n* Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy, patients with hepatitis B and C on active treatment, or those with acute hepatitis B and C not currently on treatment.\n\n  * NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.\n* Uncontrolled intercurrent illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Symptomatic congestive heart failure\n  * Unstable angina pectoris\n  * Clinically significant cardiac arrhythmia\n  * Bleeding disorder\n  * Cardiac arrhythmia\n  * Psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n  * Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy\n  * Any other conditions that would limit compliance with study requirements.\n* History of myocardial infarction ≤ 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.\n* Other active malignancy ≤ 3 years prior to registration.\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.\n  * NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer.\n* Unresolved toxicity from prior chemotherapy (subjects must be recovery to ≤ grade 1 toxicity from previous anticancer treatments or previous investigational agents).\n* Receiving any other investigational agent or device ≤ 14 days prior to registration.\n* Planning on receiving other medical, surgical, or radiological cancer treatments during the course of this study.\n* Evidence of untreated fluid retention at the time of registration (including, for example, peripheral edema, pleural effusion, or ascites on physical or radiological examination) or history of severe capillary leak syndrome.\n* Any other condition which the investigator believes would make participation in the study not acceptable.\n* Subjects with any active and\u002For symptomatic brain metastases or active primary central nervous system (CNS) and subjects with carcinomatosis meningitis are excluded.\n\n  * NOTE: History of brain metastases treated by surgery and\u002For radiotherapy provided neurologically stable and off steroids ≥ 4 weeks prior to registration are allowed.\n* Grade 2 or greater neuropathy (excluding diagnosed carpal tunnel syndrome).\n* Use of concomitant medication that are known to be inhibitors or substrates of major CYP enzymes, CYP2C9, CYP2c19, CYP3a4, CYP2D6, CYP1A2, CYP2B6 and CYP2C8 ≤ 14 days prior to registration.\n* Use of concomitant medication that are known to be inhibitors or substrates of transporters ≤ 14 days prior to registration.\n* Corrected QT (QTc) prolongation based on QTc interval prior to registration of ≥ 470 ms using the Fridericia's formula (QTcF).\n* Confluent superficial keratitis, a cornea epithelial defect, a corneal ulcer or stromal opacity.\n* Significant electrolyte imbalance.\n* Significant uncontrolled congestive heart failure.\n* Symptomatic uncontrolled cardiac arrhythmia.\n* Genetic predisposition for long QT syndrome.\n* Subjects who are receiving concomitant QT prolonging medication.",{"count":254,"type":20},42,[23],"This phase I trial tests the safety, side effects, and best dose of MTI-301 in treating patients with solid cancers that have spread from where they first started (primary site) to other places in the body (metastatic) or that cannot be removed by surgery (unresectable) and that have not responded to previous treatment (refractory). MTI-301 is a drug that inhibits an enzyme called SCD1. SCD1 is an enzyme that promotes tumor growth and spread and is upregulated in some cancer types. MTI-301 may disrupt the activity of SCD1, which may lead to reduced tumor growth and\u002For spread.",[115,30,258],"Unresectable Malignant Solid Neoplasm","2026-03-18",{"date":261,"type":37},"2026-03-19",{"date":263,"type":37},"2025-11-07",{"date":265,"type":20},"2027-04-09",{"name":267,"class":44},"Mayo Clinic",{"id":269,"slug":270,"hasResults":11,"nctId":271,"briefTitle":272,"officialTitle":273,"acronym":4,"eligibilityCriteria":274,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":275,"enrollmentInfo":276,"targetDuration":4,"studyType":21,"phases":278,"briefSummary":279,"conditions":280,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":295,"lastUpdatePostDateStruct":296,"startDateStruct":298,"completionDateStruct":300,"leadSponsor":302,"locationsCount":245},"100371641","phase-1-gene-modified-immune-cells-after-conditioning-regimen-for-the-treatment-of-stage-iiic-or-iv-melanoma-or-metastatic-solid-tumors-100371641","NCT04119024","Gene Modified Immune Cells After Conditioning Regimen for the Treatment of Stage IIIC or IV Melanoma or Metastatic Solid Tumors","Phase I Dose Escalation Study of Systemically Administered IL13Ra2 Chimeric Antigen Receptor (CAR) T Cells After a Nonmyeloablative Conditioning Regimen in Patients With Metastatic Melanoma and Other Solid Tumors","Inclusion Criteria:\n\n* Histologically confirmed malignancy that is considered surgically incurable with either:\n\n  * Stage IIIC melanoma including locally relapsed, satellite, in-transit lesions or bulky draining node metastasis\n  * Stage IV melanoma including patients with known brain metastases\n  * Other metastatic, non-central nervous system (CNS) solid tumor relapsed or refractory after all standard-of-care systemic therapies for which the patient is eligible\n* Confirmed IL13Ralpha2 tumor expression by immunohistochemistry (immunohistochemical assay \\[IHA\\] H-Score \\>= 50 in at least 10% of the total tumor specimen and in at least two high-power fields)\n* Age greater than or equal to 18 years old and less than 75 years old\n* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1\n* A minimum of one measurable lesion defined as:\n\n  * Meeting the criteria for measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST), OR\n  * Skin lesion(s) selected as non-completely biopsied target lesion(s) that can be accurately measured and recorded by color photography with a ruler to document the size of the target lesion(s)\n* Absolute neutrophil count (ANC) \\>= 1 x 10\\^9 cells\u002FL (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)\n* Platelets \\>= 75 x 10\\^9\u002FL (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)\n* Hemoglobin \\>= 9.5 g\u002FdL (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)\n* Aspartate and alanine aminotransferases (AST, ALT) =\\\u003C 2.5 x upper limit of normal (ULN) (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)\n* Total bilirubin =\\\u003C 2 x ULN (except patients with documented Gilbert's syndrome) (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)\n* Creatinine \\\u003C 2 mg\u002FdL (or a glomerular filtration rate \\> 45) (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)\n* Patients with melanoma must have progressed following \\>= 1 line of systemic therapy, including immune checkpoint inhibitor and a BRAF inhibitor in combination with MEK inhibitor for patients with BRAF V600-activating mutation and is not considered to have an alternate treatment option with curative intent\n* Must be willing and able to accept at least one leukapheresis procedure (This does not apply for patients receiving a second infusion of IL13R a2 CAR T cells as they will not undergo leukapheresis)\n* Must be willing and able to provide written informed consent\n\nExclusion Criteria:\n\n* Inability to purify \\>= 1 x 10\\^7 T cells from leukapheresis product (this does not apply to patients receiving a second infusion of IL13Ra2 CAR T cells as they will not undergo leukapheresis)\n* Previously known hypersensitivity to any of the agents used in this study; known sensitivity to cyclophosphamide or fludarabine\n* Received systemic treatment for cancer, including immunotherapy, within 14 days prior to initiation of conditioning chemotherapy administration within this protocol\n* Clinically active brain metastases. Radiological documentation of absence of active brain metastases at screening is required for all patients. Prior evidence of brain metastasis successfully treated with surgery or radiation therapy will not be exclusion for participation as long as they are deemed under control at the time of study enrollment\n* Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 2 weeks prior to enrollment; not including patients with primary or secondary adrenal insufficiency who require physiologic replacement with steroids, or patients on inhaled or topical steroids at standard doses\n* Human immunodeficiency virus (HIV) seropositivity or other congenital or acquired immune deficiency state, which would increase the risk of opportunistic infections and other complications during chemotherapy-induced lymphodepletion. If there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and\u002For infectious disease specialist\n* Hepatitis B or C seropositivity with evidence of ongoing liver damage, which would increase the likelihood of hepatic toxicities from the chemotherapy conditioning regimen and supportive treatments. If there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and\u002For infectious disease specialist\n* Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol\n* A Tiffeneau-Pinelli index \\\u003C 70% of the predicted value. Subjects will be excluded if pulmonary function tests indicate they have insufficient pulmonary capability\n* Patients will be excluded if they have a history of clinically significant electrocardiography (ECG) abnormalities, symptoms of cardiac ischemia or arrhythmias and have a left ventricular ejection fraction (LVEF) \\\u003C 45% on a cardiac stress test (stress thallium, stress multigated acquisition scan (MUGA), dobutamine echocardiogram, or other stress test)\n* Patients with ECG results of any conduction delays (PR interval \\> 200 ms, corrected QT (QTC) \\> 480 ms), sinus bradycardia (resting heart rate \\\u003C 50 beats per minute), sinus tachycardia (HR \\> 120 beats per minute) will be evaluated by a cardiologist prior to starting the trial. Patients with any arrhythmias, including atrial fibrillation\u002Fatrial flutter, excessive ectopy (defined as \\> 20 ventricular premature complex \\[PVC\\]s per minute), ventricular tachycardia, 3rd degree heart block will be excluded from the study unless cleared by a cardiologist\n* Pregnancy or breast-feeding. Female patients must be surgically sterile or be postmenopausal for two years, or must agree to use effective contraception during the period of treatment and for 6 months afterwards. All female patients with reproductive potential must have a negative pregnancy test (serum\u002Furine) at screening and again within 14 days from starting the conditioning chemotherapy. The definition of effective contraception will be based on the judgment of the study investigators. Patients who are breastfeeding are not allowed on this study\n* A concomitant active malignancy that would be considered to interfere with the assessment of the primary or secondary endpoints of the study","75 Years",{"count":277,"type":20},18,[23],"This phase I trial studies the side effects and best dose of modified immune cells (IL13Ralpha2 CAR T cells) after a chemotherapy conditioning regimen for the treatment of patients with stage IIIC or IV melanoma or solid tumors that have spread to other places in the body (metastatic). The study agent is called IL13Ralpha2 CAR T cells. T cells are a special type of white blood cell (immune cells) that have the ability to kill tumor cells. The T cells are obtained from the patient's own blood, grown in a laboratory, and modified by adding the IL13Ralpha2 CAR gene. The IL13Ralpha2 CAR gene is inserted into T cells with a virus called a lentivirus. The lentivirus allows cells to make the IL13Ralpha2 CAR protein. This CAR has been designed to bind to a protein on the surface of tumor cells called IL13Ralpha2. This study is being done to determine the dose at which the gene-modified immune cells are safe, how long the cells stay in the body, and if the cells are able to attack the cancer.",[115,281,282,283,65,30,284,285,286,287,288,289,290,291,292,293,294],"Metastatic Melanoma","Pathologic Stage IIIC Cutaneous Melanoma AJCC v8","Pathologic Stage IV Cutaneous Melanoma AJCC v8","Uveal Melanoma","Acral Melanoma","Neuroendocrine Tumors","Paraganglioma","Pheochromocytoma","Adrenocortical Carcinoma","Pancreatic Neuroendocrine Tumor","Thyroid Cancer","Breast Cancer","Lung Adenocarcinoma","Head and Neck Squamous Cell Carcinoma","2026-03-13",{"date":297,"type":37},"2026-03-17",{"date":299,"type":37},"2025-10-07",{"date":301,"type":20},"2026-10",{"name":303,"class":44},"Anusha Kalbasi",{"id":305,"slug":306,"hasResults":11,"nctId":307,"briefTitle":308,"officialTitle":309,"acronym":4,"eligibilityCriteria":310,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":311,"targetDuration":4,"studyType":21,"phases":313,"briefSummary":314,"conditions":315,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":316,"lastUpdatePostDateStruct":317,"startDateStruct":319,"completionDateStruct":321,"leadSponsor":323,"locationsCount":126},"100540712","phase-1-axatilimab-in-combination-with-retifanlimab-and-paclitaxel-for-the-treatment-of-patients-with-advanced-or-metastatic-solid-tumors-100540712","NCT06320405","Axatilimab in Combination With Retifanlimab and Paclitaxel for the Treatment of Patients With Advanced or Metastatic Solid Tumors","A Phase Ib\u002FII Study of Axatilimab in Combination With Retifanlimab and Paclitaxel for the Treatment of Patients With Advanced Solid Tumors","Inclusion Criteria:\n\n* Ability to comprehend the investigational nature of the study and provide informed consent. Written informed consent must be obtained prior to any study specific procedures or interventions\n* Age ≥ 18 years at the time of consent. All participants, irrespective of their gender, gender identity, race, and ethnicity, will be included\n* Certified, documented diagnosis of a metastatic solid tumor based on pathology review\n* Presence of at least one lesion that is measurable per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and another lesion that is amenable to tumor biopsy\n* Relapsed from, or refractory to, standard of care (SOC) systemic therapy known to prolong survival or if, in the opinion of the primary treating oncologist, a clinical trial is the best option for the next line of treatment based on response and\u002For tolerability to available therapies\n* Investigational therapy is permitted after a wash-out period of 5 half-lives (if known), or 28 days, whichever is shorter, prior to study day -8. Prior use of an investigational agent for imaging, such as T cell imaging, is permitted\n* Prior treatment with taxanes. A wash-out of period of ≥ 3 months prior to day -8 must be met for enrollment. Prior anti PD-1\u002FPD-L1 therapy is allowed, but not required\n* Eastern Cooperative Oncology Group (ECOG) status (performance status \\[PS\\]) of 0-1\n* Life expectancy of greater than 12 weeks according to certified physician review\n* Hemoglobin (Hb) ≥ 8.5 g\u002FdL\n* Leukocytes ≥ 3,000\u002FmcL\n* Absolute neutrophil count (ANC) ≥ 1,500\u002FmcL\n* Platelets ≥ 100K\u002Fcc mL\n\n  * Values must be obtained without transfusion within 2 weeks\n* Serum creatinine (sCr) \\\u003C 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 50 mL\u002Fmin (calculated with the Cockcroft-Gault formula) for participants with creatinine (sCr) levels above institutional normal\n* Total bilirubin \\\u003C 1.5 x upper limit of normal (ULN)\n\n  * With the exception of documented Gilbert's syndrome or similar conditions, at the discretion of the principal investigator (PI). Clinical chemistry testing may be adjusted, as clinically indicated\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) or alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 2.5 x ULN\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association (NYHA) Functional Classification. To be eligible for this trial, patients should be class 2B or better\n* Corrected QT interval Fridericia's formula (QTcF) of \\\u003C 480 ms on a 12 lead electrocardiogram (EKG), except for participants with atrioventricular pacemakers or other conditions (e.g., right bundle branch block) that render the QT measurement invalid\n* Willingness to modify concomitant drug regimens, at the recommendation and discretion of pharmacy services, including the use of known substrates or inhibitors of CYP2C8 and CYP3A4\n* Physiologic maintenance doses of corticosteroids (≤ 10 mg\u002Fday of prednisone or equivalent) are permitted. Examples include: Asthma treatment; topical ocular, intra-articular, or intranasal steroids with minimal systemic absorption; and brief courses of corticosteroids for prophylaxis\n* Patients with CD4+ T-cell (CD4+) counts ≥ 350 cells\u002FuL are eligible regardless of HIV serology\n\n  * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of enrollment are eligible\n  * In the case of ongoing treatment with antiretroviral therapy (ART), medication adjustment may be necessary for the duration of treatment. A wash-out period may be necessary, at the recommendation of the institutional research pharmacy service (RPS)\n* Evidence of chronic hepatitis B virus (HBV) infection (i.e., hepatitis B surface antigen \\[HBsAg\\]-positive, undetectable or low HBV deoxyribonucleic acid \\[DNA\\], and normal ALT) in the absence of HBV therapy, or serologic evidence of a resolved prior HBV infection (i.e., HBsAg-negative and hepatitis B virus core antibody \\[anti-HBc\\]-positive) is permitted\n* History of hepatitis C virus (HCV) infection is permitted given prior curative treatment or undetectable HCV viral load by serology or polymerase chain reaction (PCR) testing\n\n  * Patient who are HCV antibody (Ab) seropositive but HCV ribonucleic acid (RNA) negative due to prior treatment or natural resolution are eligible\n\nExclusion Criteria:\n\n* Secondary malignancy with documented diagnosis by a treating physician \\\u003C 3 years prior to study day -8. The following criteria also apply:\n\n  * New or progressive brain metastases. Patients with brain metastases not requiring immediate central nervous system (CNS) specific treatment or stable for at least 4 weeks prior to study day -8 are eligible at the discretion of the investigator given that neurologic symptoms are resolved.\n  * Patients with active leptomeningeal disease are not eligible\n* Palliative radiation therapy administered within 1 week prior to study day -8, Note: Participants must have recovered from all radiation-related toxicities (to grade \\\u003C 1 or baseline), must not require corticosteroids for this purpose, and must not have had radiation pneumonitis\n* Immunization with a live vaccine within 28 days prior to study day -8\n* History of organ transplantation, including hematopoietic stem cell transplantation (HSCT)\n* Clinical evidence of interstitial lung disease or active non-infectious pneumonia\n* Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (≤ 10 mg\u002Fday of prednisone or equivalent is permitted)\n* Prior National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 immune-related adverse event (irAE) that required systemic immunosuppression (endocrinopathies managed by stable doses of supplements and\u002For corticosteroids ≤ 10 mg\u002Fday are permitted)\n* Unresolved toxicities (resolution required to grade 1 or baseline) from prior anticancer therapies. The following exceptions apply:\n\n  * Alopecia, lymphopenia, grade 2 neuropathy (if not resulting in functional deficit), and grade 1 (no supplementation required) or grade 2 endocrinopathies (stable on supplements)\n* Prior allergy or severe hypersensitivity reaction to axatilimab, retifanlimab, paclitaxel, cremaphor-containing agents, and\u002For components of the drug formulations\n* Active infection requiring systemic antibiotic therapy\n* Persons of childbearing potential (PCBP) who are pregnant (i.e., positive pregnancy test within 7 days prior to study day -8) or breastfeeding are not eligible.\n\n  * The effects of the investigational regimen on the developing human fetus are unknown. For this reason, persons of reproductive potential must agree to use a highly effective form of contraception, starting with the time of consent to 4 months after the last dose of retifanlimab or 90 days after the last dose of axatilimab, whichever is longer\n  * Sperm-producing participants must not donate sperm throughout the study period and for 90 days post completion of study treatment\n* Uncontrolled, intercurrent illness and psychiatric illness\u002Fsocial situations that would limit compliance with study requirements, at the discretion of the investigator",{"count":312,"type":20},38,[23,58],"This phase I\u002FII trial tests the safety, side effects, and effectiveness of axatilimab in combination with retifanlimab and paclitaxel for the treatment of patients with a solid tumor that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Axatilimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as retifanlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Giving axatilimab in combination with retifanlimab and paclitaxel may be safe, tolerable and\u002For effective in treating patients with advanced or metastatic solid tumors.",[28,115,65,30],"2025-12-25",{"date":318,"type":37},"2025-12-29",{"date":320,"type":37},"2024-05-21",{"date":322,"type":20},"2029-04-01",{"name":324,"class":44},"OHSU Knight Cancer Institute",{"id":326,"slug":327,"hasResults":11,"nctId":328,"briefTitle":329,"officialTitle":330,"acronym":4,"eligibilityCriteria":331,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":332,"targetDuration":4,"studyType":21,"phases":334,"briefSummary":335,"conditions":336,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":343,"lastUpdatePostDateStruct":344,"startDateStruct":346,"completionDateStruct":348,"leadSponsor":350,"locationsCount":45},"100456725","phase-1-aoh1996-for-the-treatment-of-refractory-solid-tumors-100456725","NCT05227326","AOH1996 for the Treatment of Refractory Solid Tumors","First in Human Phase 1 Study of AOH1996 in Patients With Refractory Solid Tumors","Inclusion Criteria:\n\nInformed Consent and Willingness to Participate\n\n* 1\\. Documented informed consent by the participant\n* 2\\. Willingness to permit study team to obtain and use archival tissue, if already existing\n\nAge Criteria, Performance Status and Life Expectancy\n\n* 3\\. Age: ≥ 18 years\n* 4\\. ECOG performance status ≤ 2\n* 5\\. Life expectancy of \\> 3 months\n\nNature of Illness and Treatment History \\_\\_6. Patients with solid tumors failing standard therapies or patients refusing standard treatments (exception: Part B NSCLC combination (EGFR TKI + AOH1996) cohort: patients with stable disease or better on EGFR TKI for at least 2 months)\n\nContraception\n\n\\_\\_7. Agreement by females and males of childbearing potential\\* to use an adequate method of birth control (hormonal contraception is inadequate) or abstain from heterosexual activity for the course of the study through 30 days after the last dose of study medication. See Appendix B for guidelines.\n\n\\- Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \\> 1 year (women only).\n\nLaboratory Criteria (to be performed within 14 days prior to Day 1)\n\n* 8\\. ANC ≥ 1,500\u002Fmm3\n* 9\\. Platelets ≥ 100,000\u002Fmm3 :\n* 10\\. Total serum bilirubin ≤ 1.5 x ULN\n* 11\\. AST =\\\u003C 1.5 x ULN or =\\\u003C 3 x ULN with liver metastases\n* 12\\. ALT =\\\u003C 1.5 x ULN or =\\\u003C 3 x ULN with liver metastases\n* 13\\. Creatinine clearance of ≥ 60 mL\u002Fmin per 24 hour urine or the Cockcroft-Gault\n* 14\\. Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n\nExclusion Criteria\n\nConcomitant Medications\u002FTherapies \\_\\_1. Dietary\u002Fherbal supplements\n\n* 2\\. Other investigational products or chemotherapy. Exception: EGFR TKI in the NSCLC expansion cohort is allowed.\n* 3\\. Warfarin\n* 4\\. Current or planned use of agents contraindicated for use with strong CYP3A4 inducers\n* 5\\. Strong inhibitors or inducers of CYP2C9\n* 6\\. Strong inhibitors or inducers of CYP3A\n\nOther Illnesses and Conditions\n\n* 7\\. Issues with tolerating oral medication (e.g., inability to swallow pills, malabsorption issues, ongoing nausea or vomiting).\n* 8\\. Women who are or are planning to become pregnant or breastfeed\n* 9\\. Known allergy to any of the components within the study agents and\u002For their excipients.\n* 10\\. No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years.\n* 11\\. Intercurrent or historic medical condition that increases subject risk in the opinion of the Investigator. Eligibility may be revisited for intercurrent medical conditions once resolution\u002Frecovery is deemed adequate by the investigator (e.g. recovery from major surgery, completion of treatment for severe infection).\n\nNoncompliance\n\n\\_\\_12. Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility\u002Flogistics).\n\n\\*\\*Eligibility should be confirmed per institutional policies.",{"count":333,"type":20},92,[23],"This phase I trial studies the side effects and best dose of AOH1996 in treating patients with solid tumors that do not respond to treatment (refractory). AOH1996 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.",[30,337,338,339,340,341,342],"Osteosarcoma","Leiomyosarcomas","Synovial Sarcomas","Ovarian Cancer","Non-Small Cell Lung Cancer","Pancreatic Cancer","2025-09-12",{"date":345,"type":37},"2025-09-18",{"date":347,"type":37},"2022-08-12",{"date":349,"type":20},"2029-09-13",{"name":351,"class":44},"City of Hope Medical Center"]