[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"locally-advanced-gastric-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:locally-advanced-gastric-carcinoma":33},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,6,0,[8,70,99,129,164,188],{"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":57,"whyStopped":4,"lastUpdateSubmitDate":58,"lastUpdatePostDateStruct":59,"startDateStruct":62,"completionDateStruct":64,"leadSponsor":66,"locationsCount":69},"100404756","phase-2-measuring-the-effects-of-talazoparib-in-patients-with-advanced-cancer-and-dna-repair-variations-100404756",false,"NCT04550494","Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations","A Pharmacodynamics-Driven Trial of Talazoparib, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Aberrations in Genes Involved in DNA Damage Response","Inclusion Criteria:\n\n* Adult patients with solid tumors and documented germline or somatic aberrations in genes involved in DNA damage response (DDR) and whose disease has progressed following at least one standard therapy or who have no acceptable standard treatment options. Molecular testing performed at an National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) (NCT02465060) study-designated Clinical Laboratory Improvement Act (CLIA) laboratory or at Myriad Genetics, GeneDx, Invitae, or the Frederick National Laboratory for Cancer Research (FNLCR) Molecular Characterization Laboratory (MoCha) will be acceptable for determination of eligibility\n* Patients with the following germline or somatic genetic aberrations will be eligible based on compelling preclinical and\u002For clinical data suggesting that these deleterious mutations confer sensitivity to PARP inhibitors; no more than 6 patients (across both cohorts) with an eligibility mutation in any one gene will be enrolled\n\n  * Deleterious BRCA1 or BRCA2 mutations\n  * Loss of function mutations (including novel loss of function frameshift or nonsense mutations) in the following Fanconi anemia genes: FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN\n  * A known functional mutation (including novel loss of function frameshift or nonsense mutations) in any of the following DDR genes: ARID1A, ATM, ATR, BACH1 (BRIP1), BAP1, BARD1, CDK12, CHK1, CHK2, IDH1, IDH2, MRE11A, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD54L\n* Age \\>= 18 years of age\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2\n* Life expectancy of greater than 3 months\n* Leukocytes \\>= 3,000\u002FmcL\n* Absolute neutrophil count \\>= 1,500\u002FmcL\n* Platelets \\>= 100,000\u002FmcL\n* Hemoglobin \\>= 10 g\u002FdL\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (=\\\u003C 3 x upper limit of normal in the presence of documented Gilbert's syndrome or liver metastases at baseline)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) \u002F alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 3 x institutional upper limit of normal\n* Creatinine =\\\u003C 1.5 x institutional upper limit of normal OR Creatinine clearance (CrCl) \\>= 60 mL\u002Fmin\u002F1.73m\\^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL\u002Fmin\u002F1.73m\\^2\n* Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \\>= 20 mm (\\>= 2 cm) by chest x-ray or as \\>= 10 mm (\\>= 1 cm) with CT scan, MRI, or calipers by clinical exam\n* Patients must have a tumor site amenable to biopsy. If avoidable, the lesion for biopsy should not be selected as a target lesion for RECIST measurements\n* The effects of talazoparib on the developing human fetus are unknown. For this reason and because PARP inhibitors are known to be teratogenic, women of child-bearing potential must agree to use a highly effective method of contraception for the duration of study participation and for at least 7 months after completing study treatment. 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. Male patients with female partners of reproductive potential and pregnant partners who are treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation and for at least 4 months after completion of talazoparib administration\n* Patients must be able to swallow whole tablets or capsules. Nasogastric or gastric-tube (G-tube) administration is not allowed. Any gastrointestinal disease which would impair ability to swallow, retain, or absorb drug is not allowed\n* Ability to understand and the willingness to sign a written informed consent document\n* Patients must have recurrent, locally advanced or metastatic disease\n* Patients must have progressed on or after at least one line of standard-of-care (SOC) intervention, except for those patients without SOC or for whom talazoparib is SOC\n* PATIENTS WITH OVARIAN CANCER:\n* All patients with ovarian cancer should have one prior platinum-based therapy\n* Patients with ovarian cancer with platinum-sensitive disease are eligible. Patients with platinum-refractory disease are not eligible\n* Patients with gBRCAm ovarian cancer must also have progressed on a PARP inhibitor. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented\n* PATIENTS WITH PANCREATIC CANCER:\n* All patients with pancreatic cancer should have received prior platinum-containing therapy in the metastatic setting\n* PATIENTS WITH BREAST CANCER:\n* Patients with HER2+ breast cancer should have had 2 prior systemic lines of therapy in the metastatic setting, including anti-HER2 therapy\n* Patients with breast cancer who are eligible for a PARP inhibitor by Food and Drug Association (FDA) approvals must have had prior PARP inhibitor as per FDA indication. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented\n* PATIENTS WITH GASTRIC CANCER:\n* Patients with HER2+ gastric cancer should have had received anti-HER2 therapy in the metastatic setting\n* PATIENTS WITH PROSTATE CANCER:\n* Patients with prostate cancer who are eligible for a PARP inhibitor by FDA approvals must have had prior PARP inhibitor for eligibility. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented\n* All patients with prostate cancer can continue to receive treatment with gonadotropin-releasing hormone (GnRH) agonists while on study, as long as there is evidence of disease progression on prior therapy\n* Patients with castration resistant prostate cancer must have castrate levels of testosterone (\\\u003C 50 ng\u002FdL \\[1.74 nmol\u002FL\\])\n* Patients with metastatic hormone receptor (HR) prostate cancer and mutations in either BRCA1, BRCA2, or ATM should continue to receive anti-androgen receptor (anti-AR) therapy\n\nExclusion Criteria:\n\n* Patients who have had chemotherapy or radiotherapy within 4 weeks or 5 half-lives, whichever is shorter (6 weeks for nitrosoureas or mitomycin C). Patients must be \\>= 2 weeks since any prior administration of a study drug in a phase 0 or equivalent study and be \\>= 1 week from palliative radiation therapy. Patients must have recovered to eligibility levels from prior toxicity or adverse events\n* Patients who have had prior treatment with talazoparib are ineligible\n* Patients who have had prior monoclonal antibody therapy must have completed that therapy \\>= 6 weeks (or 3 half-lives of the antibody, whichever is shorter) prior to enrollment on protocol (minimum of 1 week between prior therapy and study enrollment) except for monoclonal antibody therapies that have been proven to be safe when combined with PARP inhibitor (PARPi) treatment (such as anti-PD-1\u002FPD-L1 and anti-HER2), which must be completed \\>= 4 weeks prior to enrollment\n* Patients who are receiving any other investigational agents\n* Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases, whose brain metastatic disease has remained stable for \\>= 1 month without requiring steroid and anti-seizure medication are eligible to participate\n* Eligibility of subjects receiving any medications or substances with the potential to affect the activity or pharmacokinetics of talazoparib will be determined following review by the principal investigator\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Pregnant women are excluded from this study because the effects of the study drugs on the developing fetus are unknown\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* Patients who require use of coumarin-derivative anticoagulants such as warfarin are excluded. Low-dose warfarin (=\\\u003C 1 mg\u002Fday) is permitted\n* Women who are currently lactating\n* History of prior malignancies within the past 3 years other than non-melanomatous skin cancers that have been controlled","ALL","18 Years",{"count":19,"type":20},36,"ESTIMATED","INTERVENTIONAL",[23],"PHASE2","This phase II trial studies if talazoparib works in patients with cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and has mutation(s) in deoxyribonucleic acid (DNA) damage response genes who have or have not already been treated with another PARP inhibitor. Talazoparib is an inhibitor of PARP, a protein that helps repair damaged DNA. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. All patients who take part on this study must have a gene aberration that changes how their tumors are able to repair DNA. This trial may help scientists learn whether some patients might benefit from taking different PARP inhibitors \"one after the other\" and learn how talazoparib works in treating patients with advanced cancer who have aberration in DNA repair genes.",[26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56],"Anatomic Stage III Breast Cancer AJCC v8","Anatomic Stage IV Breast Cancer AJCC v8","Castration-Resistant Prostate Carcinoma","Clinical Stage III Gastric Cancer AJCC v8","Clinical Stage IV Gastric Cancer AJCC v8","HER2-Positive Breast Carcinoma","Locally Advanced Breast Carcinoma","Locally Advanced Gastric Carcinoma","Locally Advanced Malignant Solid Neoplasm","Locally Advanced Ovarian Carcinoma","Locally Advanced Pancreatic Carcinoma","Locally Advanced Prostate Carcinoma","Metastatic Breast Carcinoma","Metastatic Gastric Carcinoma","Metastatic Malignant Solid Neoplasm","Metastatic Ovarian Carcinoma","Metastatic Pancreatic Carcinoma","Metastatic Prostate Carcinoma","Platinum-Sensitive Ovarian Carcinoma","Recurrent Breast Carcinoma","Recurrent Gastric Carcinoma","Recurrent Ovarian Carcinoma","Recurrent Pancreatic Carcinoma","Recurrent Prostate Carcinoma","Stage II Pancreatic Cancer AJCC v8","Stage III Ovarian Cancer AJCC v8","Stage III Pancreatic Cancer AJCC v8","Stage III Prostate Cancer AJCC v8","Stage IV Ovarian Cancer AJCC v8","Stage IV Pancreatic Cancer AJCC v8","Stage IV Prostate Cancer AJCC v8","RECRUITING","2026-06-18",{"date":60,"type":61},"2026-06-22","ACTUAL",{"date":63,"type":61},"2021-04-26",{"date":65,"type":20},"2026-12-01",{"name":67,"class":68},"National Cancer Institute (NCI)","NIH",4,{"id":71,"slug":72,"hasResults":11,"nctId":73,"briefTitle":74,"officialTitle":75,"acronym":4,"eligibilityCriteria":76,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":77,"targetDuration":4,"studyType":21,"phases":79,"briefSummary":81,"conditions":82,"keywords":4,"overallStatus":57,"whyStopped":4,"lastUpdateSubmitDate":90,"lastUpdatePostDateStruct":91,"startDateStruct":93,"completionDateStruct":95,"leadSponsor":97,"locationsCount":98},"100544094","phase-1-testing-the-combination-of-the-anticancer-drugs-trastuzumab-deruxtecan-ds-8201a-and-azenosertib-zn-c3-in-patients-with-stomach-or-other-solid-tumors-100544094","NCT06364410","Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors","Phase 1 Study of Trastuzumab Deruxtecan (DS-8201a) in Combination With Azenosertib (ZN-c3) in HER2-Expressing\u002FAmplified Gastric\u002FGastroesophageal Junction Cancer and Other Solid Tumors","Inclusion Criteria:\n\n* In the dose escalation, patients must have a histologically documented locally advanced, unresectable, or metastatic solid tumor that has progressed following at least one prior line of treatment in the metastatic setting or has no satisfactory alternative treatment option and all of the following:\n\n  * HER2 expression by immunohistochemistry (IHC) (1+, 2+, or 3+) or HER2 amplification by in situ hybridization (ISH) or next generation sequencing (NGS) (on any Clinical Laboratory Improvements Amendments \\[CLIA\\] platform on tissue), AND\n  * T-DXd (DS-8201a)-naive disease\n* In the dose expansion, patients must have histologically documented locally advanced, unresectable or metastatic gastric or gastroesophageal junction (GEJ) cancer that has progressed following at least one prior line of treatment in the metastatic setting and have all of the following:\n\n  * HER2 expression by IHC (1+, 2+, or 3+) or HER2 amplification by ISH or NGS (on any CLIA platform on tissue), AND\n  * T-DXd (DS-8201a)-naive disease\n  * Received prior trastuzumab-based treatment, if eligible for such treatment\n* For the dose escalation and dose expansion, patients can have evaluable or measurable disease\n* Potential trial participants should have recovered from clinically significant adverse events (AEs) of their most recent therapy\u002Fintervention prior to enrollment\n* Age ≥ 18 years. Because no dosing or AE data are currently available on the use of T-DXd (DS-8201a) in combination with azenosertib (ZN-c3) in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 (Karnofsky ≥ 70%). Both T-DXd (DS-8201a) and azenosertib (ZN-c3) have fatigue as an adverse effect. Due to the overlapping adverse effect, the performance status cannot be less restrictive\n* Absolute neutrophil count ≥ 1.5 × 10\\^9\u002FL (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Hemoglobin \\> 9.0 g\u002FdL (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Platelets ≥ 100 × 10\\^9\u002FL (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). Documented Gilbert syndrome is allowed if total bilirubin is ≤ 3 × institutional ULN (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Aspartate aminotransferase (AST \\[serum glutamic-oxaloacetic transaminase (SGOT)\\])\u002Falanine aminotransferase (ALT \\[serum glutamate pyruvate transaminase (SGPT)\\]) ≤ 3 × institutional ULN. In the presence of liver metastases, AST or ALT up to 5 × institutional ULN is permitted (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Measured of calculated creatinine clearance (CrCl) ≥ 60 mL\u002Fmin (CrCl should be calculated per institutional standard; glomerular filtration rate can also be used in place of CrCl) ≥ 60 mL\u002Fmin for patients with creatinine levels \\> 1.5 x institutional ULN (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* International normalized ratio\u002Fprothrombin time and activated partial thromboplastin time ≤ 1.5 × institutional ULN (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Patients must have left ventricular ejection fraction (LVEF) ≥ 50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before enrollment\n* Human immunodeficiency virus-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\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* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression\n* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS-specific treatment is not required and is unlikely to be required during the first cycle of study treatment\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* Life expectancy ≥ 3 months\n* Women of childbearing potential (WOCBP) must have a negative serum pregnancy test result within 3 days of study treatment initiation\n* Agents composed of HER2 antibody conjugated to a topoisomerase 1 inhibitor and azenosertib (ZN-c3) are known to be teratogenic; thus, WOCBP must agree to use highly effective contraception from time of screening and throughout the study treatment period and for at least 7 months after final study treatment administration. 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. Female patients must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period and for at least 7 months after the final study treatment administration\n* Women of non-childbearing potential defined as premenopausal females with documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \\> 40 mIU\u002FmL and estradiol \\\u003C 40 pg\u002FmL \\[\\\u003C 147 pmol\u002FL\\] is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for WOCBP if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their postmenopausal status, they can resume use of HRT during the study without use of a contraception method\n* Male patients involved with WOCBP must agree to use a highly effective form of contraception or avoid intercourse from time of screening and throughout the study treatment period and for at least 4 months after the last dose of study treatment. Male patients must not freeze or donate sperm starting at screening and throughout the study period and at least 4 months after the final study treatment administration. Preservation of sperm should be considered prior to enrollment in this study\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants\n* Willing to undergo biopsy as required by the study (dose expansion only)\n\n  * Note: Patients in the dose escalation who have insufficient\u002Finadequate archival tissue may have optional pre-treatment biopsy\n* Patients must have adequate washout from prior therapy at the time of study treatment initiation: 4 weeks from major surgery (any surgical incision should be fully healed prior to study drug administration); 4 weeks from antibody-based therapy; 2 weeks or or 5 half-lives (whichever is shorter) from any targeted therapy or small molecule therapy; 3 weeks or 5 half-lives (whichever is shorter) from chemotherapy or 6 weeks in the case of certain therapies (e.g., extensive radiotherapy, mitomycin C, and nitrosoureas); and 4 weeks from radiation therapy. These washout periods are included to ensure patients have maximal bone marrow recovery and as this is a multicenter trial, to ensure uniformity in interpretation of recovery\n\nExclusion Criteria:\n\n* As azenosertib (ZN-c3) is a substrate of CYP3A4, use of prescription or non-prescription drugs known to be moderate or strong inhibitors or inducers of CYP3A4 are prohibited with the exception of moderate or strong inhibitors or inducers of CYP3A4 that are part of the prophylactic antiemetic regimen. Chloroquine\u002Fhydroxychloroquine are metabolized by CYP3A4 and therefore, should be prohibited. For patients who have received prior moderate or strong inhibitors or inducers of CYP3A4, the required washout period is approximately 5 half-lives prior to study treatment initiation\n* Patients who are receiving any other investigational agents\n* Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs\n* Patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies (mAbs)\n* Patients with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e., rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy\n* Patients who require supplemental oxygen for activities of daily living\n* Pregnant women are excluded from this study because T-DXd (DS-8201a) and azenosertib (ZN-c3) have the potential risk for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with T-DXd (DS-8201a) and azenosertib (ZN-c3), breastfeeding should be discontinued if the mother is treated with T-DXd (DS-8201a) or azenosertib (ZN-c3)\n* Patients with history of non-infectious pneumonitis\u002Finterstitial lung disease (ILD), current ILD, or where suspected ILD cannot be ruled out by imaging at screening\n* Patients with active infections requiring treatment (antibiotic, antifungal, or antiviral) at the time of study treatment initiation are not eligible. Patients who have completed such treatment and whose infection is controlled\u002Fresolved (and afebrile) for at least 7 days before cycle 1 day 1 are eligible\n* Patients with history of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills\n* Patients with current signs or symptoms of bowel obstruction including sub-occlusive disease related to underlying disease\n* Patients with a medical history of myocardial infarction within 6 months before enrollment, symptomatic congestive heart failure (New York Heart Association class IIb to IV), and\u002For troponin levels consistent with myocardial infarction as defined according to the manufacturer 28 days prior to enrollment\n* Patients with clinically significant corneal disease\n* Patients with a pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART). (Drainage and CART are not allowed within 2 weeks prior to screening assessment)\n* Patients with history of Torsades de Pointes unless all risk factors that contributed to Torsades de Pointes have been corrected\n* Based on an average of triplicate 12-lead electrocardiogram (ECG), patients with a mean resting corrected QT (QTc) interval using Fridericia formula of \\> 470 msec for both males and females at screening or a history of congenital long QT syndrome will be excluded\n* Patients with prior treatment with a WEE1 inhibitor (dose escalation and dose expansion)\n* Patients with prior treatment with T-DXd (DS-8201a) or other topoisomerase inhibitors (dose escalation and dose expansion)\n* Patients with uncontrolled intercurrent illness\n* Patients with prior allogeneic organ transplantation including allogeneic stem cell transplantation\n* Patients with clinically significant chronic gastrointestinal disorder with diarrhea as a major symptom; ≥ grade 2 diarrhea at baseline. Please contact the protocol principal investigator (PI) for any patient with more than two episodes of diarrhea per day averaged over at least a 7-day period at time of screening to determine whether the diarrhea would be considered clinically significant\n* Patients with spinal cord compression",{"count":78,"type":20},48,[80],"PHASE1","This phase I trial tests the safety, side effects, and best dose of azenosertib in combination with trastuzumab deruxtecan in treating patients with HER2-positive gastric or gastroesophageal junction cancer and other HER2-positive solid tumors that have spread to nearby tissue or lymph nodes (locally advanced), that have spread from where it first started (primary site) to other places in the body (metastatic), or that cannot be removed by surgery (unresectable). Azenosertib is in a class of medications called kinase inhibitors. It inhibits a protein called Wee1. Inhibition of the Wee1 protein can make tumor cells more vulnerable to chemotherapy drugs, leading to tumor cell death. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers deruxtecan to kill them. Giving azenosertib in combination with trastuzumab deruxtecan may be safe, tolerable, and\u002For more effective in treating patients with locally advanced, metastatic, or unresectable HER2-positive gastric, gastroesophageal junction, or other solid tumors, compared to just trastuzumab deruxtecan alone.",[29,83,30,84,33,85,34,39,86,40,87,88,89],"Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Locally Advanced Gastroesophageal Junction Adenocarcinoma","Metastatic Gastroesophageal Junction Adenocarcinoma","Unresectable Gastric Carcinoma","Unresectable Gastroesophageal Junction Adenocarcinoma","Unresectable Malignant Solid Neoplasm","2026-06-16",{"date":92,"type":61},"2026-06-17",{"date":94,"type":61},"2025-02-03",{"date":96,"type":20},"2027-07-08",{"name":67,"class":68},1,{"id":100,"slug":101,"hasResults":11,"nctId":102,"briefTitle":103,"officialTitle":104,"acronym":105,"eligibilityCriteria":106,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":107,"enrollmentInfo":108,"targetDuration":4,"studyType":21,"phases":110,"briefSummary":112,"conditions":113,"keywords":114,"overallStatus":57,"whyStopped":4,"lastUpdateSubmitDate":119,"lastUpdatePostDateStruct":120,"startDateStruct":122,"completionDateStruct":124,"leadSponsor":126,"locationsCount":98},"100484853","phase-3-transarterial-neoadjuvant-chemotherapy-vstraditional-intravenous-chemotherapy-for-locally-advanced-gastric-cancer-with-soxpd-1-100484853","NCT05593458","Transarterial Neoadjuvant Chemotherapy vs.Traditional Intravenous Chemotherapy For Locally Advanced Gastric Cancer With SOX+PD-1","A Multicenter, Randomized, Controlled Study of S-1 Combined With Oxaliplatin by Arterial Infusion Plus PD-1 Antibody Versus Conventional SOX Chemotherapy Plus PD-1 Antibody for Locally Advanced Gastric Cancer","TACTIC","Inclusion Criteria:\n\n* Eastern Cooperative Oncology Group(ECOG) score 0-1\n* Ambulatory males or females, aged 18-75 years\n* Histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (Siewert type II or III)\n* Locally advanced gastric carcinoma (cT3N2-3M0, cT4aN1-3M0, cT4bNanyM0, American Joint Committee on Cancer (AJCC) TNM staging system 8th edition)\n* Life expectancy more than 3 months\n* Give written informed consent, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.\n* Normal hepatic, renal, and bone marrow function (ALT\u002FAST\\\u003C2.5 fold of upper limit value;Tbil\\\u003C1.5mg\u002Fdl, Cr\\\u003C1.5 fold of upper limit value; White Blood Cell count≥3 × 10\\^9\u002FL, ANC ≥ 1.5 × 10\\^9\u002FL,PLT≥ 80 × 10\\^9\u002FL,Hb ≥ 90 g\u002FL).\n\nExclusion Criteria:\n\n* Patients can not bear surgical procedure.\n* Pregnant or lactating women.\n* HER2 overexpression(+++) confirmed by immunohistochemistry.\n* Previous cytotoxic chemotherapy, radiotherapy or immunotherapy.\n* History of another malignancy within the last five years.\n* History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the Investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake.\n* Clinically significant (i.e. active) cardiac disease e.g. symptomatic coronary artery disease, New York Heart Association (NYHA) grade II or greater congestive heart failure or serious cardiac arrhythmia requiring medication or myocardial infarction within the last 12 months.\n* History of dysphagia, complete or partial gastrointestinal obstruction, active gastrointestinal bleeding and gastrointestinal perforation;\n* Organ allografts requiring immunosuppressive therapy.\n* Serious uncontrolled intercurrent infections or other serious uncontrolled concomitant disease.\n* Moderate or severe renal impairment: serum creatinine \\> 1.5 x upper limit of normal (ULN).\n* Hypersensitivity to any drug of the study regimen.\n* With abdominal cavity implantation metastasis or distant metastasis.\n* Unwilling or unable to comply with the protocol for the duration of the study.","75 Years",{"count":109,"type":20},190,[111],"PHASE3","SOX regimen, consisting of oral S-1 and intravenous oxaliplatin, is the preferred regimen for perioperative chemotherapy for gastric cancer. The goal of this clinical trial is to compare the efficacy and safety between S-1 combined with oxaliplatin by arterial infusion, as neoadjuvant chemotherapy, and conventional SOX regimen, in locally advanced gastric cancer. The main question it aims to answer is: whether arterially infused oxaliplatin plus S-1 has the potential to be a better neoadjuvant option for patients with locally advanced gastric cancer.\n\nParticipants will be randomised, and receive:\n\n* 3 cycles of conventional SOX chemotherapy plus PD-1 antibody or arterial infused oxaliplatin plus S-1 and PD-1 antibody, as neoadjuvant chemotherapy;\n* Adequate gastric resection along with D2 lymph node dissection;\n* 3 cycles adjuvant chemotherapy using SOX regimen plus PD-1 antibody.\n* Administration of S-1 regularly till 1 year after surgery.\n\nResearchers will compare Major pathological response rate (MPR) ，pathologic complete response rate（pCR）,the 2-year overall survival (OS) rates, 2-year disease free survival (DFS), R0 resection rates, and adverse events, to see if the modified perioperative chemotherapy improve the prognosis of patients with locally advanced gastric cancer.",[33],[115,116,117,118],"gastric cancer","arterial infusion","neoadjuvant therapy","immunotherapy","2026-06-08",{"date":121,"type":61},"2026-06-11",{"date":123,"type":61},"2023-03-01",{"date":125,"type":20},"2026-12",{"name":127,"class":128},"Zhejiang University","OTHER",{"id":130,"slug":131,"hasResults":11,"nctId":132,"briefTitle":133,"officialTitle":134,"acronym":4,"eligibilityCriteria":135,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":136,"targetDuration":4,"studyType":21,"phases":138,"briefSummary":139,"conditions":140,"keywords":150,"overallStatus":57,"whyStopped":4,"lastUpdateSubmitDate":155,"lastUpdatePostDateStruct":156,"startDateStruct":158,"completionDateStruct":160,"leadSponsor":162,"locationsCount":98},"100493464","phase-2-olanzapine-for-the-management-of-cancer-associated-appetite-loss-in-patients-with-advanced-esophagogastric-hepatopancreaticobiliary-colorectal-or-lung-cancer-100493464","NCT05705492","Olanzapine for the Management of Cancer Associated Appetite Loss in Patients With Advanced Esophagogastric, Hepatopancreaticobiliary, Colorectal or Lung Cancer","ACTO: A Phase II, Randomized, Placebo-Controlled Study Evaluating Olanzapine in the Management of Cancer Cachexia","Inclusion Criteria:\n\n* Willingness to provide written informed consent\n* Individuals \\>= 18 years of age\n* Histologically confirmed advanced local or metastatic esophogastric, hepatopancreaticobiliary, colorectal, or lung cancer diagnosis within 12 weeks of screening\n* Patients with weight loss as defined by international consensus criteria (documented or patient-reported):\n\n  * ≥ 5% weight loss over the past 6 months\n  * ≥ 2% weight loss with body mass index (BMI) \\\u003C20 kg\u002Fm\\^2 or sarcopenia\n* Planned or ongoing first-line palliative antineoplastic therapy (cytotoxic chemotherapy, targeted therapy, immunotherapy, combinations) with or without radiation therapy and have not started the second cycle of first-line palliative antineoplastic therapy. Patients may have received adjuvant antineoplastic therapy at least 6 months prior to screening\n* Able to ambulate independently with or without assistive devices (e.g., cane, walker)\n* In the case of brain metastases, the individual must be asymptomatic or previously treated with a full cycle of therapy with recovery from any acute effects of radiation therapy or surgery before screening. Such individuals must have discontinued corticosteroid treatment and be neurologically stable for at least 4 weeks before screening\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2\n* Able and willing to discontinue the use of any drug or over-the-counter (OTC) product that may interact with the study drug (within a period sufficient for wash-out per the principal investigators \\[PI's\\] discretion) and thereafter while on the study\n* Willingness to comply with restrictions on chest\u002Fbreastfeeding\n* Individuals capable of childbearing and contributing viable sperm must be willing to comply with contraception requirements and not donate ova or sperm while on the study and for 1 month after that\n* A negative pregnancy test at baseline (BL) must be obtained for individuals capable of childbearing\n\nExclusion Criteria:\n\n* Plan for, or history of (within 30 days of enrollment), the use of an antipsychotic drug, including, but not limited to, risperidone, quetiapine, clozapine, phenothiazine, or butyrophenone. This limitation does not include prochlorperazine and other phenothiazines as antiemetic therapy. The use of antipsychotics concurrent with protocol therapy will not be allowed\n* Current use of medications or supplements with the goal of enhancing appetite within ≥14 days, including:\n\n  * megestrol acetate\n  * cannabinoids (including, but not limited to dronabinol, medical cannabis, over the counter \\[OTC\\] cannabinoid products), and\u002For\n  * Corticosteroids (defined as ≥ 5mg of prednisone \\[or equivalent per day\\]), except for standard-of-care chemotherapy-induced nausea and vomiting prophylaxis\n* Known history of poorly controlled diabetes, defined as fasting morning blood sugars ≥300 mg\u002FdL or recent hemoglobin A1≥ 8. Individuals with diabetes will undergo hemoglobin A1c (HbA1c) blood testing if they do not have HbA1c results 12 weeks prior to enrollment\n* Inadequate organ function, which may include, but is not limited to, the following laboratory results within 28 days before signing consent:\n\n  * Total bilirubin ≥5x upper limit of normal (ULN), aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SPGT\\]) ≥5X ULN (unless the participant has documented Gilbert's syndrome, hepatocellular carcinoma, or hepatic metastases)\n  * Primary investigator (PI) discretion will determine continued eligibility after randomization occurs in the event the liver function test results are above the proposed ULN\n  * Renal disease requiring dialysis or calculated glomerular filtration rate (GFR) ≤ 30 mL\u002Fminute\u002F1.73 m\\^2 as calculated by the modification of diet in renal disease (MDRD) equation\n* Tube feeding or parenteral nutrition at the time of screening\n* Any condition that may negatively impact oral absorption of the study drug (including, but not limited to dysphagia, mucositis, gastrectomy, colitis, bowel obstruction, high output ileostomy) or any plan to undergo an intervention that will render such a condition\n* Recurrent ascites unresponsive to medical interventions and requires therapeutic paracentesis\n* Uncontrolled symptoms at randomization make the individual unsuitable for the study in the judgment of the PI. If uncontrolled symptoms can be effectively palliated for ≥1 week prior, enrollment may be considered at the discretion of the PI\n* Uncontrolled infection, including coronavirus disease 2019 (COVID-19), at time of randomization. Individuals with the uncontrolled infection will not be eligible as the symptomology of infection may obscure the outcomes of this study\n* Other medical or psychiatric condition, including recent (within 1 year) or active suicidal ideation\u002Fbehavior or laboratory abnormality, may increase the risk of study participation or, in the PI's judgment, makes the participant inappropriate for the study",{"count":137,"type":20},66,[23],"This phase II trial tests how well olanzapine works in managing cancer cachexia in patients experiencing esophagogastric, hepatopancreaticobiliary, colorectal, or lung cancer 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) -associated appetite loss while receiving non-curative cancer therapy. Loss of appetite (\"anorexia\") in the setting of cancer is a key feature of \"cachexia,\" a syndrome associated with loss of weight and muscle as well as weakness and fatigue. Olanzapine is a drug that targets key neurotransmitters (a type of molecule in the central nervous system that transmits messages to the rest of the body) that may stimulate appetite, restore caloric intake, minimize weight loss, and improve quality of life (QOL).",[141,142,143,144,145,146,33,147,148,149],"Advanced Malignant Solid Neoplasm","Advanced Biliary Tract Carcinoma","Advanced Esophageal Carcinoma","Metastatic Esophageal Carcinoma","Locally Advanced Colorectal Carcinoma","Locally Advanced Esophageal Carcinoma","Metastatic Colorectal Carcinoma (mCRC)","Advanced Lung Carcinoma","Locally Advanced Hepatocellular Carcinoma",[151,152,153,154],"cancer","cachexia","weight loss","loss of appetite","2026-01-19",{"date":157,"type":61},"2026-01-21",{"date":159,"type":61},"2024-07-17",{"date":161,"type":20},"2026-12-31",{"name":163,"class":128},"OHSU Knight Cancer Institute",{"id":165,"slug":166,"hasResults":11,"nctId":167,"briefTitle":168,"officialTitle":169,"acronym":4,"eligibilityCriteria":170,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":171,"enrollmentInfo":172,"targetDuration":174,"studyType":175,"phases":4,"briefSummary":176,"conditions":177,"keywords":4,"overallStatus":57,"whyStopped":4,"lastUpdateSubmitDate":179,"lastUpdatePostDateStruct":180,"startDateStruct":182,"completionDateStruct":184,"leadSponsor":186,"locationsCount":98},"100572032","first-line-and-neoadjuvant-immunotherapy-for-gastric-cancer-100572032","NCT06727981","First-Line and Neoadjuvant Immunotherapy for Gastric Cancer","Prospective Cohort Study on the Efficacy, Adverse Effects, and Biomarkers of First-Line\u002FNeoadjuvant Therapy With Immune Checkpoint Inhibitors Combined With Chemotherapy in Advanced Gastric Cancer","Inclusion Criteria:\n\n1. Age 18 years old or above\n2. Patients with advanced gastric cancer or locally advanced gastric cancer\n3. Have not received any previous anti-tumor therapy\n4. Patients expected to receive immunotherapy for first-line or neoadjuvant therapy\n5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1\n6. Adequate organ function\n\nExclusion Criteria:\n\n1. Patients with contraindications to immunotherapy\n2. Have received anti-tumor treatments such as immunotherapy and chemotherapy\n3. Have a history of active immune deficiency or autoimmune diseases, including HIV positive test, or have other acquired or congenital immune deficiency diseases, or have a history of organ transplantation or autoimmune diseases\n4. Severe chronic or active infection requires systemic antibacterial, antifungal, or antiviral treatment, including tuberculosis infection. Have a history of active tuberculosis infection ≥ 1 year before recruitment should also be excluded, unless proved has been completed appropriate treatment\n5. History of allogeneic stem cell transplantation or organ transplantation","100 Years",{"count":173,"type":20},500,"1 Year","OBSERVATIONAL","This prospective observational study aims to evaluate the efficacy and safety of immune checkpoint inhibitors as first-line and neoadjuvant therapy for advanced gastric cancer, while also investigating relevant biomarkers to better understand their role in immunotherapy outcomes",[178,33],"Advanced Gastric Cancer","2024-12-10",{"date":181,"type":61},"2024-12-11",{"date":183,"type":61},"2022-01-15",{"date":185,"type":20},"2028-01-15",{"name":187,"class":128},"Qilu Hospital of Shandong University",{"id":189,"slug":190,"hasResults":11,"nctId":191,"briefTitle":192,"officialTitle":193,"acronym":4,"eligibilityCriteria":194,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":195,"enrollmentInfo":196,"targetDuration":4,"studyType":21,"phases":198,"briefSummary":199,"conditions":200,"keywords":4,"overallStatus":57,"whyStopped":4,"lastUpdateSubmitDate":203,"lastUpdatePostDateStruct":204,"startDateStruct":206,"completionDateStruct":208,"leadSponsor":210,"locationsCount":98},"100430894","phase-2-toripalimab-plus-flot-in-locally-advanced-gastric-cancer-100430894","NCT04891016","Toripalimab Plus FLOT in Locally Advanced Gastric Cancer","Toripalimab Combined With FLOT Regimen in Locally Advanced Gastric cancer-a Prospective, Open, Multi-center, Phase Ⅱ Clinical Study","Inclusion Criteria:\n\n* 70 ≥ Age ≥ 18 years regardless of gender\n* Gastric adenocarcinoma confirmed by pathology\n* no distant metastasis and resectable or potentially resectable evaluated by general surgery experts\n* ECOG PS 0-1\n* clinical stage T3\u002F4 or N+ by AJCC 8.0\n* PD-L1 CPS ≥1 (IHC 22C3 pharm Dx assay (Dako))\n* expected lifespan over 3 months\n* Adequate organ function: 1) without growth factor and blood component support in the first 2 weeks of enrollment; 2) Cardiac function: no heart disease or coronary heart disease, grade 1-2; 3) liver function: TBIL ≤ 2ULN, AST ≤ 2.5 ULN, alt ≤ 2.5 ULNX 4 Renal function: cr ≤ 1.25ULN, liver function: TBIL ≤ 2ULN, TBIL ≤ 2.5ULN, alt ≤ 2.5ULN, 4)renal function: cr ≤ 1.25ULN.\n* blood pressure normal or controlled within the normal range by antihypertensive drugs\n* Diabetic patients were treated with hypoglycemic drugs to control fasting blood glucose ≤ 8mmol\u002FL\n* Patients with positive hepatitis B surface antigen need to be tested for quantitative detection of hepatitis B DNA virus. HBV DNA should be less than the upper limit of the normal test value for patients with HBV infection.\n* no other serious diseases conflicting with this study\n* No history of other malignant tumors\n* Women of childbearing age must be tested negative for blood pregnancy test within 7 days before enrollment, and subjects of childbearing age must use appropriate contraceptive measures during the trial and within 6 months after the trial\n* agreement to participate in this study and signed the informed consent form\n\nExclusion Criteria:\n\n* Pregnant or lactating women\n* Suffered from severe infectious diseases within 4 weeks before entering the group\n* Bronchial asthma requires intermittent use of bronchodilators or medical intervention\n* Due to the use of immunosuppressants before coexisting diseases and the dosage of immunosuppressants ≥ 10mg\u002F, the oral dose of prednisone lasted for more than 2 weeks\n* Clinically obvious cardio-cerebrovascular diseases, including, but not limited to, severe acute myocardial infarction, instability or severe angina pectoris, coronary artery bypass surgery, congestive heart failure, ventricular arrhythmias requiring medical intervention, left ventricular ejection fraction \\\u003C 50%, stroke within 6 months\n* Allergic to any experimental drug and its excipients, or have a history of severe allergy, or are contraindications to experimental drugs\n* Severe mental disorders\n* Abnormal coagulation function (PT \\> 16s, APTT \\> 53s, TT \\> 21s Fib \\\u003C 1.5g\u002FL), bleeding tendency or undergoing thrombolysis or anticoagulation therapy\n* Past or present pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, severe impairment of lung function, etc.\n* Unable to swallow research drugs, chronic diarrhea (including but not limited to irritable bowel syndrome, Crohn's disease, ulcerative colitis) and intestinal obstruction affect drug use and absorption\n* Have a history of immunodeficiency, including positive for HIV, or suffer from other acquired, congenital immunodeficiency diseases, or have a history of organ transplant\n* Other researchers evaluate those who do not meet the criteria for admission","70 Years",{"count":197,"type":20},60,[23],"Neoadjuvant chemoimmunotherapy for locally advanced gastric and gastroesophageal junction (G\u002FGEJ) cancer is currently under investigation. Most clinical studies have simply combined chemotherapy with anti-PD-1 therapy without considering the impact of chemotherapy drugs on activated immune cells. We designed this study to explore two different treatment regimens for neoadjuvant chemotherapy in patients with locally advanced G\u002FGEJ cancer. One group received FLOT plus toripalimab on Day 1 of each cycle, every 2 weeks for 4 cycles, followed by surgery; the other group received FLOT plus toripalimab on Day 3 of each cycle, every 3 weeks for 3 cycles, followed by surgery. A total of 69 subjects were enrolled. Preliminary statistical analysis conducted one year after the last subject was enrolled revealed no statistically significant differences in pCR and MPR between the two regimens. The median DFS for both groups has not been reached, and there is no statistically significant difference in DFS between the two groups at present. Further subgroup analysis indicated that among subjects with PD-L1 CPS ≥1, the triweekly group achieved a rate of 42.1%, compared to 29.4% in the biweekly group, with no statistically significant difference between the two groups. However, the incidence of bone marrow suppression was lower in the triweekly group than in the biweekly group. Based on the preliminary findings, we plan to conduct an expanded study and transition to a multicenter clinical trial. This study aims to further validate the efficacy of the triweekly chemoimmunotherapy in patients with PD-L1 CPS ≥1 locally advanced G\u002FGEJ cancer.",[201,202,33],"Chemotherapy","Immune Checkpoint Inhibitor","2024-06-05",{"date":205,"type":61},"2024-06-06",{"date":207,"type":61},"2021-06-25",{"date":209,"type":20},"2028-12-31",{"name":211,"class":212},"Henan Cancer Hospital","OTHER_GOV"]