[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"pmmr\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:pmmr":29},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,3,0,[8,45,74],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":34,"startDateStruct":37,"completionDateStruct":39,"leadSponsor":41,"locationsCount":44},"100581422","phase-2-scrt-capeox-serplulimab-for-msspmmr-rectal-cancer-with-oligometastases-100581422",false,"NCT06850103","SCRT-CAPEOX-Serplulimab for MSS\u002FpMMR Rectal Cancer With Oligometastases","A Phase II Exploratory Multicenter Randomized Controlled Clinical Trial to Evaluate the Effectiveness of Neoadjuvant Short-Course Radiotherapy (SCRT) Followed by CAPEOX Chemotherapy and Serplulimab in Microsatellite Stable (MSS) or Proficient Mismatch Repair (pMMR) Rectal Cancer With Synchronous Oligometastases","Inclusion Criteria:\n\n\\- Has signed the written Informed Consent Form (ICF) and is able to comply with protocol-specified visits and procedures.\n\nAge between 18-75 years.\n\nHistologically confirmed primary rectal adenocarcinoma, with MRI showing tumor location within 10cm from the anal verge.\n\nSynchronous oligometastatic rectal cancer confirmed by comprehensive imaging evaluation (contrast-enhanced CT, contrast-enhanced MRI, PET-CT, etc.), with ≤2 metastatic sites and ≤5 total metastatic lesions.\n\nMicrosatellite stability status confirmed as MSS (using the NCI-recommended 5 microsatellite markers: BAT25, BAT26, D5S346, D2S123, D17S250) or proficient mismatch repair (pMMR) status confirmed by immunohistochemistry showing positive nuclear expression of all 4 MMR proteins (MLH1, MSH2, MSH6, PMS2).\n\nAt least one measurable lesion according to RECIST v1.1 criteria.\n\nEastern Cooperative Oncology Group performance status (ECOG PS) of 0-1.\n\nAdequate organ function and bone marrow reserve, defined as follows:\n\nComplete blood count:\n\nAbsolute Neutrophil Count (ANC) ≥1.5×109\u002FL Platelet count (PLT) ≥100×109\u002FL Hemoglobin (HGB) ≥10.0g\u002FdL\n\nLiver function:\n\nTotal Bilirubin (TBIL) ≤1.5×Upper Limit of Normal (ULN) Alanine transaminase (ALT) and Aspartate aminotransferase (AST) ≤3×ULN Serum albumin (ALB) ≥35 g\u002FL\n\nRenal function:\n\nSerum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL\u002Fmin (calculated using Cockcroft-Gault formula \\[see Appendix 3\\] or standard 24-hour urine collection method) Urine protein by dipstick \\\u003C2+ For subjects with baseline urine protein ≥2+ by dipstick, 24-hour urine protein must be \\\u003C1g\n\nCoagulation:\n\nInternational Normalized Ratio (INR) ≤1.5 Activated partial thromboplastin time (APTT) ≤1.5×ULN Certain anticoagulant medications (such as antiplatelet agents, vitamin K antagonists) must be discontinued 7-14 days before surgery and replaced with alternative medications (such as low molecular weight heparin) No concurrent serious diseases that would threaten subject survival (leading to expected survival \\\u003C5 years).\n\nWomen of childbearing potential and men whose partners are of childbearing potential must use effective contraception during the entire treatment period and for 6 months after treatment completion. Female subjects must either have evidence of post-menopausal status, or if pre-menopausal, have a negative urine or serum pregnancy test.\n\nExclusion Criteria:\n\n\\- More than 2 metastatic sites or more than 5 total metastatic lesions confirmed by imaging evaluation.\n\nPrior anti-tumor therapy for the study disease, including surgery, radiotherapy, chemotherapy, targeted therapy, or immunotherapy.\n\nPrevious treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies, or any other drugs targeting T-cell co-stimulation or immune checkpoint pathways (e.g., OX40, CD137), or adoptive cell immunotherapy.\n\nConcurrent participation in another clinical trial, except for observational (non-interventional) studies or survival follow-up phase of interventional studies.\n\nReceipt of any investigational drug within 4 weeks prior to first dose of study drug.\n\nHistory of blood transfusion or use of G-CSF, GM-CSF, EPO, TPO, or IL-11 within 14 days prior to screening laboratory tests.\n\nUse of immunosuppressive medications within 4 weeks prior to first dose of study drug, excluding:\n\nIntranasal inhaled corticosteroids or local steroid injections Systemic corticosteroids at ≤10 mg\u002Fday prednisone equivalent Corticosteroids as premedication for allergic reactions (e.g., CT contrast) Traditional Chinese medicines with anti-tumor indications or immunomodulatory effects within 1 week prior to first dose Receipt of live or attenuated vaccines within 4 weeks prior to first dose or anticipated during the study period.\n\nMajor surgery within 4 weeks prior to first dose (e.g., craniotomy, thoracotomy, or laparotomy), anticipated major surgery during treatment (excluding protocol-specified rectal cancer surgery), or presence of unhealed wounds, ulcers, or fractures.\n\nKnown active or suspected autoimmune disease or history within past 2 years (exceptions: eczema, vitiligo, psoriasis, alopecia, or Graves' disease not requiring systemic treatment in past 2 years; hypothyroidism requiring only hormone replacement; Type I diabetes requiring only insulin).\n\nKnown history of primary immunodeficiency.\n\nActive tuberculosis, current anti-TB treatment, or anti-TB treatment within 1 year prior to first dose.\n\nKnown history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.\n\nKnown allergy to capecitabine, oxaliplatin, serplulimab, or other monoclonal antibody components.\n\nClinically significant ascites, pleural effusion requiring intervention, or symptomatic pericardial effusion requiring drainage.\n\nHIV infection (HIV antibody positive).\n\nAcute or chronic active hepatitis B (defined as HBsAg positive or HBcAb positive only with HBV DNA ≥2000 IU\u002FmL or ≥1×104 copies\u002FmL) or hepatitis C (defined as HCV antibody positive with detectable HCV RNA).\n\nActive syphilis infection requiring treatment.\n\nSevere infection within 4 weeks prior to first dose, including but not limited to hospitalization for infection, bacteremia, or severe pneumonia; therapeutic oral or IV antibiotics within two weeks prior to first dose.\n\nSymptomatic congestive heart failure (NYHA class II-IV) or LVEF \\\u003C50%; symptomatic or uncontrolled arrhythmias; congenital long QT syndrome or QTc \\>500 ms at screening (Fridericia's formula).\n\nUncontrolled hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg) despite standard therapy, history of hypertensive crisis or encephalopathy.\n\nSevere bleeding diathesis or coagulation disorders, or current thrombolytic therapy.\n\nAny arterial thromboembolic events within 6 months prior to first dose, including myocardial infarction, unstable angina, stroke, or TIA.\n\nEsophageal or gastric varices requiring immediate intervention; high bleeding risk subjects require endoscopic evaluation within 3 months before enrollment.\n\nHistory of GI perforation and\u002For fistula within 6 months prior to first dose.\n\nLife-threatening bleeding event within 3 months prior to first dose, or Grade 3\u002F4 GI\u002Fvariceal bleeding requiring transfusion, endoscopy, or surgery.\n\nHistory of DVT, PE, or other serious thromboembolism within 3 months prior to first dose (excluding catheter-related thrombosis or superficial thrombosis).\n\nUncontrolled metabolic disorders or other non-malignant conditions causing high medical risk or uncertain survival evaluation.\n\nHepatic encephalopathy, hepatorenal syndrome, or Child-Pugh B \\>7 or worse cirrhosis.\n\nBowel obstruction (including incomplete requiring parenteral nutrition); conditions with perforation risk; history of extensive bowel resection, Crohn's disease, ulcerative colitis, or chronic diarrhea.\n\nInterstitial lung disease requiring treatment; history of pulmonary fibrosis, pneumoconiosis, drug-induced pneumonitis, organizing pneumonia, or severe pulmonary dysfunction.\n\nSignificant malnutrition (5% weight loss within 1 month or 15% within 3 months of consent, or \\>50% reduced intake for 1 week), unless corrected for ≥4 weeks before first dose.\n\nHistory of other primary malignancies, except:\n\nCured malignancies with ≥2 years disease-free and low recurrence risk Well-treated non-melanoma skin cancer or lentigo maligna Well-treated carcinoma in situ\n\nOther acute or chronic conditions that could:\n\nIncrease study participation risks Interfere with result interpretation Make subject unsuitable per investigator judgment Neurological, psychiatric, or social conditions affecting compliance or safety assessment.\n\nAlcohol, drug, or substance abuse affecting drug administration or toxicity analysis.\n\nPregnant or breastfeeding women.\n\nConditions interfering with medication management or toxicity analysis due to alcohol, drug, or substance use.\n\nPregnancy or breastfeeding.","ALL","18 Years","75 Years",{"count":20,"type":21},51,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","Background and Significance:\n\nColorectal cancer (CRC) ranks as the third most common cancer and the second leading cause of cancer-related deaths globally. Despite improved early screening rates, a significant proportion of newly diagnosed CRC patients present with synchronous metastases, predominantly liver metastases. The concept of oligometastases, introduced by Hellman and Weichselbaum in 1995, describes a transitional state between localized disease and widespread metastases, characterized by limited metastatic lesions (typically 1-5) confined to 1-2 organs.\n\nCurrent Treatment Landscape:\n\nThe management of oligometastatic disease combines local therapeutic approaches (surgery, radiotherapy, radiofrequency ablation) with systemic treatments, aiming to achieve No Evidence of Disease (NED) status. The ESMO guidelines officially categorized metastatic CRC into oligometastatic and widespread metastatic states in 2016, emphasizing the importance of integrated local and systemic treatments for oligometastatic colorectal liver metastases (CRLM).\n\nTreatment Evolution and Challenges:\n\nWhile the EPOC study established CAPEOX neoadjuvant chemotherapy followed by R0 resection as the standard treatment for initially resectable CRLM, patients with synchronous rectal cancer oligometastases present unique challenges due to complex local anatomy and high local recurrence risks. Although various neoadjuvant approaches, including Total Neoadjuvant Therapy (TNT), have been studied, they have not demonstrated significant long-term survival benefits, primarily because distant metastases impact survival more significantly than local recurrence.\n\nInnovative Approach:\n\nRecent success with Immunotherapy-Based Total Neoadjuvant Therapy (iTNT) in microsatellite stable\u002Fproficient mismatch repair (MSS\u002FpMMR) locally advanced rectal cancer has shown promising results. Short-course radiotherapy (SCRT) combined with chemotherapy and immunotherapy has demonstrated superior efficacy trends, attributed to radiation's immune-activating effects on both local and distant tumor microenvironments.\n\nResearch Objective:\n\nThis project aims to evaluate the effectiveness of iTNT combined with SCRT in MSS\u002FpMMR rectal cancer patients with synchronous oligometastases. The novel approach integrates SCRT with CAPEOX chemotherapy and Serplulimab, potentially improving complete response rates, organ preservation opportunities, and overall treatment efficacy while reducing recurrence risks. This pioneering study represents the first investigation of iTNT in synchronous rectal cancer oligometastases, offering a potentially transformative treatment strategy for this challenging patient population.\n\nResearch Innovation:\n\nThe study uniquely combines SCRT, CAPEOX chemotherapy, and Serplulimab in a neoadjuvant setting for MSS\u002FpMMR synchronous rectal cancer oligometastases, addressing an unmet clinical need and potentially establishing a new treatment paradigm in this field.",[27,28,29,30,31],"Colorectal Carcinoma","Oligometastases","pMMR","MSS","iTNT","RECRUITING","2026-03-22",{"date":35,"type":36},"2026-03-25","ACTUAL",{"date":38,"type":36},"2025-04-22",{"date":40,"type":21},"2032-12",{"name":42,"class":43},"First Affiliated Hospital of Zhejiang University","OTHER",1,{"id":46,"slug":47,"hasResults":11,"nctId":48,"briefTitle":49,"officialTitle":50,"acronym":4,"eligibilityCriteria":51,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":52,"targetDuration":4,"studyType":22,"phases":54,"briefSummary":55,"conditions":56,"keywords":59,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":65,"lastUpdatePostDateStruct":66,"startDateStruct":68,"completionDateStruct":70,"leadSponsor":72,"locationsCount":44},"100495479","phase-2-serplulimab-combined-with-capeox--celecoxib-as-neoadjuvant-treatment-for-locally-advanced-rectal-cancer-100495479","NCT05731726","Serplulimab Combined With CAPEOX + Celecoxib as Neoadjuvant Treatment for Locally Advanced Rectal Cancer","A Phase II Study to Explore the Neoadjuvant Treatment of Serplulimab Combined With CAPEOX + Celecoxib in the Treatment of Locally Advanced Rectal Cancer","Inclusion Criteria:\n\n1. Willing and able to provide written informed consent.\n2. Male or female subjects ≧ 18 years ≦ 75 of age.\n3. Histological or cytological documentation of adenocarcinoma of the rectum.\n4. No previous any systemic anticancer therapy for rectal cancer disease.\n5. The lower margin of the tumor is less than 10cm from the anus verge.\n6. cT2N1-2M0, cT3N0-2M0, cT4N0-2M0 MSS with MRF(-) assessed by MRI.\n7. Primary tumor can be detected by CT or MRI.\n8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n9. Eligible tumor tissues were identified for MSI\u002FMMR assays.\n10. Hepatitis B Surface Antigen (HBsAg) (-).\n11. If HBsAg (+) , HBV-DNA must be less than 2500 copies\u002FmL or 500 IU\u002FmL to be enrolled.\n12. Patients with HCV antibody (-) or HCV-RNA negative can be enrolled. Aspartate aminotransferase (AST) must be ≤ 3 x ULN for the lab. If HCV-RNA is positive, patients with both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) performed ≤3×ULN could be enrolled. Patients infected with both hepatitis B virus and hepatitis C virus should be excluded (positive for HBsAg or HBcAb and positive for HCV antibodies).\n\nExclusion Criteria:\n\n1. Patients with recurrent rectal cancer or a history of pelvic radiotherapy.\n2. Patients with a history of inflammatory bowel disease.\n3. Patients with acquired immunodeficiency syndrome (AIDS-related illnesses) or known human immunodeficiency virus (HIV) disease (HIV1 antibody, HIV2 antibody, HTLV1 antibody positive) should be excluded.\n4. Patients who are preparing for or have previously received an organ or bone marrow transplant.\n5. History of myocardial infarction, poorly controlled arrhythmias (including QTc interval ≥470 ms in women) in the 6 months prior to enrollment (QTc interval calculated by Fridericia formula).\n6. According to New York College of Cardiology (NYHA) standards for Grade III-IV cardiac insufficiency or cardiac color ultrasound: left ventricular ejection fraction (LVEF) \\\u003C50%.Poor hypertension control (systolic blood pressure ≥150 mmHg and\u002For diastolic blood pressure ≥100 mmHg), a past hypertensive crisis or hypertensive encephalopathy.\n7. Poor hypertension control (systolic blood pressure ≥150 mmHg and\u002For diastolic blood pressure ≥100 mmHg), a past hypertensive crisis or hypertensive encephalopathy.\n8. Patients had undergone major surgery within 28 days prior to enrollment. Patients with tumor biopsy or lymph node dissection biopsy were admitted. Patients undergoing enterostomy due to intestinal obstruction were admitted.\n9. The patients had previously been treated with other antibodies\u002Fdrugs that target immune checkpoints, such as PD-1, PD-L1, and cytotoxic T lymphocyte-associated Antigen 4 (CTLA-4).\n10. Patients are participating in other clinical studies, or plan to start this study treatment less than 14 days from the end of the previous clinical study.\n11. Uncontrolled tumor-related pain.\n12. A known history of severe allergy to any monoclonal antibody.\n13. Known to be allergic or intolerance to any oxaliplatin and capecitabine ingredients.\n14. Pregnant or lactating women.\n15. The investigators determined that the patient had other factors that might have led to the early termination of the study.",{"count":53,"type":21},50,[24],"Colorectal cancer of Mismatch Repair-proficient (pMMR)\u002F Microsatellite Stability (MSS) accounts for approximately 85% of all colorectal cancer patients, which might be insensitive to immunotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy, such as CAPEOX regimen, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Celecoxib, a COX-2 inhibitor, can improve the immune microenvironment and have a potential to synergy with immunotherapy. Chemotherapy can improve the immunogenicity of cancer cells that might enhance the efficacy of immunotherapy. The aim of this study is to explore whether chemotherapy and cyclooxygenase (COX) inhibitors combined with anti-PD-1 monoclonal antibody (mAb) could improve efficacy for resectable colorectal cancer patient with the pMMR\u002FMSS phenotype.",[29,30,57,58],"MSI-L","Locally Advanced Rectal Carcinoma",[60,61,62,63,64],"Rectal cancer","Serplulimab","Celecoxib","CAPEOX","neoadjuvant therapy","2026-03-03",{"date":67,"type":36},"2026-03-05",{"date":69,"type":36},"2023-02-22",{"date":71,"type":21},"2026-12-30",{"name":73,"class":43},"Zhejiang University",{"id":75,"slug":76,"hasResults":11,"nctId":77,"briefTitle":78,"officialTitle":79,"acronym":80,"eligibilityCriteria":81,"healthyVolunteers":11,"sex":82,"minAge":17,"maxAge":83,"enrollmentInfo":84,"targetDuration":4,"studyType":22,"phases":85,"briefSummary":87,"conditions":88,"keywords":4,"overallStatus":91,"whyStopped":4,"lastUpdateSubmitDate":92,"lastUpdatePostDateStruct":93,"startDateStruct":95,"completionDateStruct":96,"leadSponsor":98,"locationsCount":44},"100621760","immunotherapy-efficacy-targeting-endometrial-cancer-100621760","NCT07374809","IMMUNOTHERAPY EFFICACY TARGETING ENDOMETRIAL CANCER","DISSECTING THE EPIGENOME AND MICROENVIRONMENT TO UNDERSTAND IMMUNOTHERAPY EFFICACY TARGETING ENDOMETRIAL CANCER (DEMETER PROJECT)","DEMETER","Inclusion Criteria:\n\n* Female patients ≥ 18 years old.\n* Histologically confirmed epithelial endometrial carcinoma (endometrioid, serous, clear cell, mixed, or carcinosarcoma).\n* Advanced (stage III-IV) or recurrent disease, eligible for surgery or biopsy as part of the therapeutic plan.\n* Availability of fresh-frozen or OCT-embedded tumor tissue obtained at surgery\u002Fbiopsy and stored in the IEO Biobank.\n* Mismatch-repair-deficient (dMMR) or -proficient (pMMR) molecular subtype (when available).\n* Written informed consent for participation and use of biological material for translational research purposes.\n\nExclusion Criteria:\n\n* Mesenchymal tumors or epithelial tumors of non-endometrial origin (e.g., ovarian, cervical).\n* Prior systemic treatment with immune checkpoint inhibitors for other malignancies.\n* Insufficient or poor-quality tumor tissue available for molecular analyses.\n* Active or uncontrolled infection with HIV, HBV, or HCV.\n* Any condition that, in the investigator's judgment, would compromise patient safety or study integrity.","FEMALE","120 Years",{"count":53,"type":21},[86],"NA","Endometrial carcinoma (EC) represents the most common gynecological malignancy in developed countries. Despite therapeutic advances, patients with advanced or recurrent disease still have a poor prognosis, with high recurrence rates and a 5-year survival of less than 20%.\n\nRecently, four phase III studies (RUBY, NRG-GY018, AtTEnd, and DUO-E) have demonstrated that the addition of anti-PD-1\u002FPD-L1 immunotherapy to first-line chemotherapy significantly improves progression-free survival, particularly in tumors with altered DNA repair mechanisms known as mismatch repair (MMR) (so-called mismatch repair-deficient or dMMR tumors), but with benefits also observed in a subset of tumors with normal MMR function (so-called MMR-proficient or pMMR tumors). However, despite the clinical approval of these therapies, reliable biomarkers capable of predicting response to immunotherapy are still lacking.\n\nThis project aims to comprehensively characterize the genomic, epigenetic, and lipid properties of the tumor and the tumor microenvironment (TME) in order to identify predictive markers of response to immunotherapy, thereby laying the foundation for a personalized therapeutic approach in endometrial carcinoma.",[89,29,90],"Endometrial Carcinoma (EC)","DMMR Cancer","NOT_YET_RECRUITING","2026-01-21",{"date":94,"type":36},"2026-01-29",{"date":92,"type":21},{"date":97,"type":21},"2027-11-30",{"name":99,"class":43},"European Institute of Oncology"]