[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"immune-checkpoint-therapy\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:immune-checkpoint-therapy":25},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,8,0,[8,39,65,84,105,122,143,162],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":4,"eligibilityCriteria":14,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":17,"targetDuration":4,"studyType":20,"phases":21,"briefSummary":23,"conditions":24,"keywords":4,"overallStatus":26,"whyStopped":4,"lastUpdateSubmitDate":27,"lastUpdatePostDateStruct":28,"startDateStruct":31,"completionDateStruct":33,"leadSponsor":35,"locationsCount":38},"100541994","strict---surveillance-with-troponin-during-immune-checkpoint-therapy-100541994",false,"NCT06337097","STRICT - Surveillance With TRoponin During Immune Checkpoint Therapy","Inclusion Criteria:\n\n* Male or female patient ≥18 years old\n* Plan for treatment with an immune checkpoint inhibitor as standard of care even if patient is also on an additional investigational cancer therapeutic\n* Willingness to provide informed consent\n\nExclusion Criteria:\n\n* Troponin T not available at screening or prior to randomization\n* Inability to comply with planned study procedures\n* Major adverse cardiovascular event included in the primary outcome within the 30 days prior to enrollment\n* Any medical condition that could interfere with, or for which the treatment might interfere with the conduct of the study or interpretation of the study results, or that would, in the opinion of the investigator, increase the risk of the participant by participating in the study\n* Any factors that, in the Investigator's opinion, are likely to interfere with study procedures, such as history of noncompliance with scheduled appointments.","ALL","18 Years",{"count":18,"type":19},980,"ESTIMATED","INTERVENTIONAL",[22],"NA","To learn if monitoring blood levels of heart injury (troponin levels) in cancer participants treated with immune checkpoint inhibitors will lead to decreased heart-related side effects.",[25],"Immune Checkpoint Therapy","RECRUITING","2026-01-16",{"date":29,"type":30},"2026-01-20","ACTUAL",{"date":32,"type":30},"2024-02-02",{"date":34,"type":19},"2028-12-31",{"name":36,"class":37},"M.D. Anderson Cancer Center","OTHER",1,{"id":40,"slug":41,"hasResults":11,"nctId":42,"briefTitle":43,"officialTitle":43,"acronym":44,"eligibilityCriteria":45,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":46,"enrollmentInfo":47,"targetDuration":4,"studyType":20,"phases":49,"briefSummary":51,"conditions":52,"keywords":4,"overallStatus":26,"whyStopped":4,"lastUpdateSubmitDate":56,"lastUpdatePostDateStruct":57,"startDateStruct":59,"completionDateStruct":61,"leadSponsor":63,"locationsCount":38},"100614398","phase-2-node-sparing-low-dose-radiotherapy-concurrent-with-chemotherapy-and-pd-1-inhibitor-in-pmmrmss-high-risk-locally-advanced-colon-cancer-a-prospective-single-arm-phase-ii-trial-100614398","NCT07279077","Node-Sparing Low-Dose Radiotherapy Concurrent With Chemotherapy and PD-1 Inhibitor in pMMR\u002FMSS High-Risk Locally Advanced Colon Cancer: A Prospective, Single-Arm, Phase II Trial","MODIFI-L","Inclusion Criteria:\n\n1. Voluntarily signed written informed consent.\n2. Age ≥ 18 years and ≤ 75 years at the time of enrollment.\n3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.\n4. Life expectancy \\> 2 years.\n5. Histologically confirmed adenocarcinoma of the colon (without squamous or sarcomatoid components).\n6. Tumor biopsy immunohistochemistry (IHC) indicates pMMR (proficient Mismatch Repair), defined as positive expression of all four proteins: MSH1, MSH2, MSH6, and PMS2; or genetic testing indicates MSS (Microsatellite Stable).\n7. Staged as T4 and\u002For N+ (Stage IIB-III) according to the AJCC 8th edition, as evaluated by imaging (contrast-enhanced CT or MRI).\n8. Prior to enrollment, the subject must be evaluated by a surgeon responsible for the operation based on medical history to confirm eligibility for R0 resection with curative intent.\n9. No prior systemic or local anti-tumor therapy for colon cancer before study treatment, including radiotherapy, chemotherapy, immunotherapy, biologics, small molecule targeted therapy, etc.\n10. Subjects agree to the collection of tumor tissue and peripheral blood samples required during the screening period and the study process for use in related research.\n11. Adequate organ function:\n\n    a) Hematology (no use of blood components or cell growth factors within 7 days prior to the start of study treatment): i. Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹\u002FL (1,500\u002Fmm³). ii. Platelet count ≥ 100 × 10⁹\u002FL (100,000\u002Fmm³). iii. Hemoglobin ≥ 90 g\u002FL. b) Renal: i. Calculated Creatinine Clearance (CrCl) ≥ 50 mL\u002Fmin (calculated using the Cockcroft-Gault formula: CrCl (mL\u002Fmin) = {(140 - Age) × Weight (kg) × 0.85 \\[if female\\]} \u002F (Serum Creatinine (mg\u002FdL) × 72)).\n\n    ii. Urine protein \\\u003C 2+ or 24-hour urine protein quantification \\\u003C 1.0 g. c) Hepatic: i. Serum Total Bilirubin (TBil) ≤ 1.5 × ULN (Upper Limit of Normal). ii. AST and ALT ≤ 2.5 × ULN. iii. Serum Albumin (ALB) ≥ 28 g\u002FL. d) Coagulation: i. International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN.\n\n    e) Cardiac Function: i. Left Ventricular Ejection Fraction (LVEF) ≥ 50%.\n12. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to study treatment (if the urine test result cannot confirm negativity, a serum pregnancy test is required, and the serum result prevails). If a female subject of childbearing potential engages in sexual activity with a non-sterilized male partner, she must use an acceptable method of contraception starting from screening and agree to continue using it for 120 days after the last dose of the study drug; cessation of contraception after this point should be discussed with the investigator. Periodic abstinence and rhythm methods are not acceptable forms of contraception.\n\n    1. Women of childbearing potential are defined as women who have not undergone surgical sterilization (i.e., bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or are not postmenopausal (menopause is defined as at least 12 consecutive months of amenorrhea without an alternative medical cause, with serum Follicle-Stimulating Hormone \\[FSH\\] levels within the laboratory reference range for postmenopausal women).\n    2. Highly effective contraception refers to methods with a low failure rate (e.g., less than 1% per year) when used consistently and correctly. Not all contraceptive methods are highly effective. In addition to barrier methods, female subjects of childbearing potential must independently use a hormonal contraceptive method (e.g., birth control pills) to ensure pregnancy does not occur.\n13. Subjects are willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study requirements.\n\nExclusion Criteria:\n\n1. Presence of suspicious metastatic lesions or locally advanced unresectable disease, regardless of disease stage.\n2. Subjects who have had other malignancies within 5 years prior to enrollment, excluding colorectal cancer. This excludes subjects with other malignancies cured by local therapy, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the breast.\n3. Receipt of any investigational drug or investigational device therapy within 4 weeks prior to the first dose of the study drug.\n4. Presence of intestinal obstruction, bowel perforation, or intestinal bleeding requiring emergency surgical intervention.\n5. Multiple primary colorectal cancers.\n6. History of pelvic or abdominal radiotherapy.\n7. Inability to swallow pills, malabsorption syndrome, or any condition affecting gastrointestinal absorption.\n8. Prior receipt of any systemic or local anti-tumor therapy for locally advanced colon cancer, including radical surgery, chemotherapy, radiotherapy, immunotherapy (including immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy, or any therapy targeting tumor immune mechanisms), biologics, small molecule targeted therapy, etc.\n9. Receipt of non-specific immunomodulatory therapy (e.g., interleukins, interferons, thymosin, tumor necrosis factor, etc., excluding IL-11 used for thrombocytopenia) within 2 weeks prior to study treatment; receipt of traditional Chinese medicine or herbal preparations with anti-tumor indications within 1 week prior to study treatment.\n10. Active autoimmune disease requiring systemic treatment (e.g., disease-modifying antirheumatic drugs, corticosteroids, immunosuppressants) within the past two years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency) is not considered systemic treatment.\n11. History of non-infectious pneumonitis or pneumonia requiring systemic glucocorticoid treatment, or current history of interstitial lung disease.\n12. History of severe bleeding tendency or coagulation disorders; patients requiring prior or current long-term anticoagulation therapy (e.g., atrial fibrillation patients meeting CHADS2 score ≥ 2).\n13. Current uncontrolled comorbidities, including but not limited to decompensated liver cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer disease or gastritis, or psychiatric\u002Fsocial conditions that would limit the subject's compliance with study requirements or affect their ability to provide written informed consent.\n14. History of myocarditis, cardiomyopathy, or malignant arrhythmia.\n\n    1. Within 12 months prior to study treatment: unstable angina requiring hospitalization, congestive heart failure, or vascular disease (e.g., aortic aneurysm requiring surgical repair or peripheral venous thrombosis), or other cardiac damage that may affect the safety evaluation of the study drug (e.g., poorly controlled arrhythmia, myocardial infarction, or ischemia).\n    2. Within 6 months prior to study treatment: history of esophageal\u002Fgastric varices, severe ulcer, unhealed wound, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding.\n    3. Within 6 months prior to study treatment: any arterial thromboembolic event, NCI CTCAE v5.0 Grade 3 or higher venous thromboembolism, transient ischemic attack (TIA), cerebrovascular accident (stroke), hypertensive crisis, or hypertensive encephalopathy.\n    4. Within 1 month prior to study treatment: acute exacerbation of chronic obstructive pulmonary disease (COPD).\n    5. Current hypertension with systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite oral antihypertensive medication.\n15. Active or documented history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea).\n16. Severe infection within 4 weeks prior to study treatment, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; active infection requiring systemic anti-infective treatment within 10 days prior to study treatment (excluding antiviral treatment for Hepatitis B or C).\n17. Major surgery or severe trauma within 30 days prior to study treatment; minor local surgery within 3 days prior to study treatment (excluding Peripherally Inserted Central Catheter \\[PICC\\] or Central Venous Catheter \\[CVC\\] placement).\n18. History of immunodeficiency; positive HIV antibody test; currently receiving long-term systemic corticosteroids or other immunosuppressants.\n19. Known active tuberculosis (TB); subjects suspected of having active TB must undergo clinical examination to exclude it (e.g., sputum smear, chest X-ray); known active syphilis infection.\n20. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.\n21. Untreated active Hepatitis B subjects (HBsAg positive and HBV-DNA \\> 1000 copies\u002FmL \\[200 IU\u002FmL\\] or above the lower limit of detection); subjects with Hepatitis B are required to receive anti-HBV treatment during the study treatment period. Active Hepatitis C subjects (HCV antibody positive and HCV-RNA levels above the lower limit of detection).\n22. Receipt of live vaccines within 30 days prior to study treatment, or planned receipt of live vaccines during the study period.\n23. Known allergy to any component of the study drugs; known history of severe hypersensitivity reactions to other monoclonal antibodies.\n24. Known history of psychiatric illness, drug abuse, alcohol abuse, or substance abuse.\n25. Pregnant or lactating women.\n26. Prior or current presence of any disease, treatment, or laboratory abnormality that may confound study results, affect the subject's full participation in the study, or where participation is not in the subject's best interest.\n27. Local or systemic diseases not caused by malignancy; or diseases\u002Fsymptoms secondary to the tumor that lead to high medical risk and\u002For uncertainty in survival evaluation, such as tumor-related leukemoid reaction (WBC \\> 20 × 10⁹\u002FL), manifestations of cachexia (e.g., known weight loss of \\> 10% in the 3 months prior to screening), BMI ≤ 18 (BMI = Weight \\[kg\\] \u002F Height \\[m²\\]), etc.","75 Years",{"count":48,"type":19},38,[50],"PHASE2","Most colorectal cancers belong to the microsatellite stable (MSS) or proficient mismatch repair (pMMR) subtypes, with limited response to PD-1 inhibitors. Radiotherapy can increase the release of tumor-associated antigens, thereby improve responsiveness to PD-1 blockade in MSS\u002FpMMR rectal cancer. Tumor-draining lymph nodes are important sites for PD-1 inhibitors to exert antitumor effects, and studies have reported that direct radiation-induced damage and fibrosis can inhibit lymph node drainage and anti-tumor function. Accumulating evidence indicates that low-dose radiotherapy reprograms the tumor microenvironment (TME), transforming immunosuppressive 'cold' tumors into immunostimulatory 'hot' tumors. This transition is mediated by modulating the gut microbiota, eliciting innate and adaptive immune responses, inhibiting immunosuppressive cells, and promoting the infiltration of T and B lymphocytes.Therefore, this study aims to evaluate whether node-sparing low-dose radiotherapy (1Gy\u002F8f) concurrent with chemotherapy and PD-1 inhibitor can improve the pathological complete response (pCR) rate, enhance tolerability, and improve prognosis in patients with pMMR\u002FMSS high-risk locally advanced colon cancer.",[53,54,25,55],"Colon Cancer","Neoadjuvant Therapies","Radiation Therapy","2025-12-24",{"date":58,"type":30},"2025-12-26",{"date":60,"type":30},"2025-11-26",{"date":62,"type":19},"2031-12-30",{"name":64,"class":37},"Sixth Affiliated Hospital, Sun Yat-sen University",{"id":66,"slug":67,"hasResults":11,"nctId":68,"briefTitle":69,"officialTitle":69,"acronym":70,"eligibilityCriteria":71,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":46,"enrollmentInfo":72,"targetDuration":4,"studyType":20,"phases":74,"briefSummary":75,"conditions":76,"keywords":4,"overallStatus":26,"whyStopped":4,"lastUpdateSubmitDate":56,"lastUpdatePostDateStruct":78,"startDateStruct":79,"completionDateStruct":81,"leadSponsor":83,"locationsCount":38},"100610673","phase-2-node-sparing-hypofractionated-radiotherapy-plus-chemotherapy-and-pd-1-inhibitor-in-pmmrmss-high-risk-locally-advanced-colon-cancer-a-prospective-randomized-phase-ii-trial-100610673","NCT07230639","Node-Sparing Hypofractionated Radiotherapy Plus Chemotherapy and PD-1 Inhibitor in pMMR\u002FMSS High-Risk Locally Advanced Colon Cancer: A Prospective, Randomized, Phase II Trial","MODIFI-CC","Inclusion Criteria:\n\n1. Voluntarily signs a written informed consent form.\n2. Age ≥ 18 and ≤ 75 years at enrollment.\n3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n4. Life expectancy \\> 2 years.\n5. Histologically confirmed colon adenocarcinoma (without squamous or sarcomatoid components).\n6. Tumor biopsy by immunohistochemistry indicating pMMR, i.e., MLH1, MSH2, MSH6, and PMS2 all positive, or genomic testing indicating MSS.\n7. Per AJCC 8th edition, imaging (contrast-enhanced CT or contrast-enhanced MRI) shows T4 and\u002For N+ disease (stage IIB-III).\n8. Prior to enrollment, the subject must be evaluated by a surgery attending physician responsible for the operation, based on medical history, to confirm eligibility for R0 resection with curative intent.\n9. No prior systemic or local antitumor therapy for rectal cancer before study treatment, including radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy.\n10. Subject agrees to collection and study use of required tumor tissue and peripheral blood specimens during screening and throughout the study.\n11. Adequate organ function:\n\n    a) Hematologic (no blood components or hematopoietic growth factors within 7 days before starting study treatment): i. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹\u002FL (1,500\u002Fmm³); ii. Platelets ≥ 100 × 10⁹\u002FL (100,000\u002Fmm³); iii. Hemoglobin ≥ 90 g\u002FL. b) Renal: i. Calculated creatinine clearance (CrCl) ≥ 50 mL\u002Fmin using the Cockcroft-Gault formula: CrCl (mL\u002Fmin) = {(140 - age) × weight (kg) × 0.85} \u002F \\[72 × serum creatinine (mg\u002FdL)\\] ii. Urine protein \\\u003C 2+ or 24-hour urine protein \\\u003C 1.0 g. c) Hepatic: i. Total bilirubin (TBil) ≤ 1.5 × ULN; ii. AST and ALT ≤ 2.5 × ULN; iii. Serum albumin (ALB) ≥ 28 g\u002FL. d) Coagulation: i. INR and aPTT ≤ 1.5 × ULN. e) Cardiac: i. Left ventricular ejection fraction (LVEF) ≥ 50%.\n12. Women of childbearing potential (WOCBP) must have a urine or serum pregnancy test within 3 days prior to starting study treatment (if the urine test cannot be definitively interpreted as negative, a serum test is required; the serum result prevails) and the result must be negative. If a WOCBP has sexual intercourse with a non-sterilized male partner, she must begin using an acceptable contraceptive method from screening and agree to continue contraception for 120 days after the last dose of study drug; whether contraception can be discontinued thereafter should be discussed with the investigator. Periodic abstinence and calendar\u002Frhythm methods are unacceptable.\n\n    1. WOCBP are defined as females who have not undergone surgical sterilization (i.e., bilateral tubal ligation, bilateral oophorectomy, or total hysterectomy) and have not been postmenopausal (amenorrhea for ≥12 consecutive months without an alternative medical cause, with serum FSH in the postmenopausal range).\n    2. A highly effective method of contraception is one with a low failure rate when used consistently and correctly (e.g., \\\u003C1% per year). Not all methods are highly effective. Barrier methods alone are not acceptable; WOCBP must at minimum use a hormonal contraceptive (e.g., oral contraceptives) to ensure no pregnancy occurs.\n13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study requirements.\n\n    \\------\n\nExclusion Criteria:\n\n1. Suspicious metastatic lesions or the presence of unresectable locally advanced disease, regardless of stage.\n2. Malignancy other than colorectal cancer within 5 years prior to enrollment. Subjects cured by local therapy for other malignancies (e.g., basal or squamous cell skin cancer, superficial bladder cancer, ductal carcinoma in situ) are not excluded.\n3. Receipt of any investigational drug or device within 4 weeks prior to the first dose of study drug.\n4. Intestinal obstruction, perforation, gastrointestinal bleeding, or other conditions requiring emergency surgery.\n5. Multiple primary colorectal cancers.\n6. Prior radiotherapy to the pelvis or abdomen.\n7. Inability to swallow tablets, malabsorption syndrome, or any condition that affects gastrointestinal absorption.\n8. Any prior systemic or local antitumor therapy for locally advanced colon cancer, including curative surgery, chemotherapy, radiotherapy, immunotherapy (including immune checkpoint inhibitors\u002Fagonists or cellular immunotherapy), biologics, or small-molecule targeted therapy.\n9. Nonspecific immunomodulatory therapy within 2 weeks before study treatment (e.g., interleukins, interferons, thymosin, tumor necrosis factor; excluding IL-11 used for thrombocytopenia); antitumor-indicated traditional Chinese herbal medicines or patent medicines within 1 week before study treatment.\n10. Active autoimmune disease requiring systemic therapy within the past 2 years (e.g., with disease-modifying agents, corticosteroids, or immunosuppressants). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroids for adrenal or pituitary insufficiency) is not considered systemic therapy.\n11. History of or current non-infectious pneumonitis requiring systemic corticosteroids, or a history of interstitial lung disease.\n12. History of significant bleeding tendency or coagulopathy; prior or current long-term anticoagulation (e.g., atrial fibrillation with CHADS₂ score ≥ 2).\n13. Uncontrolled comorbid conditions, including but not limited to decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer disease or gastritis, or psychiatric\u002Fsocial conditions that would limit compliance with study requirements or ability to provide written informed consent.\n14. History of myocarditis, cardiomyopathy, or malignant arrhythmias. Within 12 months prior to study treatment: unstable angina requiring hospitalization, congestive heart failure, or vascular disease (e.g., aortic aneurysm requiring surgical repair or peripheral venous thrombosis), or other cardiac damage that may affect evaluation of study-drug safety (e.g., poorly controlled arrhythmias, myocardial infarction or ischemia); within 6 months prior: esophagogastric varices, severe ulcers, unhealed wounds, gastrointestinal perforation, enteric fistula, intestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding; within 6 months prior: any arterial thromboembolic event, NCI CTCAE v5.0 grade ≥3 venous thromboembolism, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy; within 1 month prior: acute exacerbation of COPD; current hypertension with SBP ≥160 mmHg or DBP ≥100 mmHg despite oral antihypertensive therapy.\n15. Active or past history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) or chronic diarrhea.\n16. Serious infection within 4 weeks before study treatment, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; active infection requiring systemic anti-infective therapy within 10 days before study treatment (excluding antiviral therapy for hepatitis B or C).\n17. Major surgery or severe trauma within 30 days before study treatment; minor local surgery within 3 days before study treatment (excluding peripherally inserted central catheter placement).\n18. History of immunodeficiency; positive HIV antibody; or current long-term systemic corticosteroid or other immunosuppressive therapy.\n19. Known active tuberculosis (TB). Subjects with suspected active TB must be clinically ruled out (e.g., sputum for mycobacteria, chest imaging). Known active syphilis infection.\n20. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.\n21. Untreated active hepatitis B (HBsAg-positive with HBV-DNA \\> 1,000 copies\u002FmL \\\\\\[200 IU\u002FmL\\] or above the assay lower limit). Subjects with hepatitis B must receive antiviral therapy during the study; active hepatitis C (HCV-antibody positive with HCV-RNA above the assay lower limit).\n22. Live vaccine within 30 days before study treatment or planned receipt of a live vaccine during the study.\n23. Known allergy to any component of the study drugs; history of severe hypersensitivity to other monoclonal antibodies.\n24. Known psychiatric illness, substance abuse, alcoholism, or drug dependence.\n25. Pregnant or breastfeeding women.\n26. Any prior or current disease, therapy, or laboratory abnormality that may confound study results, interfere with full participation, or not be in the subject's best interest to participate.\n27. Local or systemic disease not due to malignancy, or tumor-related conditions\u002Fsymptoms that may confer high medical risk and\u002For uncertainty in survival assessment, such as leukemoid reaction due to tumor (WBC \\> 20 × 10⁹\u002FL), cachexia (e.g., \\>10% body-weight loss within 3 months before screening), or BMI ≤ 18 (BMI = weight\\[kg\\] \u002F height \\[m²\\]).",{"count":73,"type":19},52,[50],"Most colorectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes, which show limited efficacy to PD-1 inhibitors. Radiotherapy can enhance the release of tumor-associated antigens, thereby improving the responsiveness of pMMR\u002FMSS colorectal cancers to PD-1 blockade. Tumor-draining lymph nodes (TDLNs) are critical sites where PD-1 inhibitors exert their antitumor effects; however, previous studies have reported that direct radiation-induced damage and fibrosis may impair lymphatic drainage and antitumor immunity. Early reports have demonstrated a remarkable pathological complete response (pCR) rate of 77.8% with lymph node-sparing short-course radiotherapy (25 Gy in 5 fractions) in locally advanced rectal cancer. In metastatic colorectal cancer, single-fraction high-dose irradiation (6-8 Gy) has been shown to induce robust abscopal effects. Based on these findings, our study aims to evaluate whether lymph node-sparing hypofractionated radiotherapy (25 Gy\u002F5F or 24 Gy\u002F4F) followed sequentially by chemotherapy and PD-1 blockade can increase the pCR rate, improve tolerability, and ultimately enhance outcomes in patients with pMMR\u002FMSS high-risk locally advanced colon cancer.",[54,25,77],"Radiotherapy",{"date":58,"type":30},{"date":80,"type":30},"2025-08-30",{"date":82,"type":19},"2031-12-31",{"name":64,"class":37},{"id":85,"slug":86,"hasResults":11,"nctId":87,"briefTitle":88,"officialTitle":89,"acronym":4,"eligibilityCriteria":90,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":46,"enrollmentInfo":91,"targetDuration":4,"studyType":20,"phases":93,"briefSummary":95,"conditions":96,"keywords":4,"overallStatus":26,"whyStopped":4,"lastUpdateSubmitDate":98,"lastUpdatePostDateStruct":99,"startDateStruct":101,"completionDateStruct":103,"leadSponsor":104,"locationsCount":38},"100589746","phase-2-node-sparing-short-course-radiotherapy-plus-chemotherapy-bevacizumab-and-pd-1-inhibitor-in-metastatic-pmmrmss-colorectal-cancer-modifi-crc-100589746","NCT06958419","Node-Sparing Short-Course Radiotherapy Plus Chemotherapy, Bevacizumab and PD-1 Inhibitor in Metastatic pMMR\u002FMSS Colorectal Cancer (MODIFI-CRC)","Node-Sparing Short-Course Radiotherapy Followed by First-Line Chemotherapy Plus Bevacizumab and PD-1 Inhibitor Versus Chemotherapy Plus Bevacizumab Alone in Metastatic pMMR\u002FMSS Colorectal Cancer: A Randomized, Phase II\u002FIII Trial (MODIFI-CRC)","Inclusion Criteria:\n\n* Voluntarily signs a written informed consent form.\n\n  * Aged between 18 and 75 years at the time of enrollment.\n  * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n  * Expected survival of more than 3 months.\n  * Histologically or cytologically confirmed colorectal adenocarcinoma.\n  * Patients must be considered unsuitable for curative surgical resection or local treatment and must not have received prior systemic anti-tumor therapy for recurrent or metastatic disease. Patients with prior neoadjuvant or adjuvant therapy may be enrolled if recurrence or metastasis occurs ≥12 months after the last dose of such treatment.\n  * At least one measurable lesion per RECIST v1.1 that can be accurately measured repeatedly. Note: Brain metastases cannot be used as target lesions.\n  * Able to provide 10-20 unstained tumor tissue FFPE slides from recent biopsy or archival material stored within 3 years. Ten slides will be used for immunohistochemistry and ten for genomic testing (recent biopsy preferred). If samples are of insufficient quality (as determined by the central lab), additional slides may be required. If adequate slides cannot be provided, partial or full waiver may be granted upon approval by the medical monitor.\n  * Agrees to provide tumor tissue and peripheral blood samples during screening and throughout the study for research purposes.\n  * Adequate organ function as defined below:\n  * Hematologic (no use of blood products or growth factors within 7 days prior to treatment):\n  * Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹\u002FL\n  * Platelet count ≥ 100 × 10⁹\u002FL\n  * Hemoglobin ≥ 90 g\u002FL\n  * Renal:\n  * Calculated creatinine clearance (CrCl) ≥ 50 mL\u002Fmin (Cockcroft-Gault formula: CrCl = \\[(140 - age) × weight (kg) × 0.85 (if female)\\] \u002F \\[72 × serum creatinine (mg\u002FdL)\\])\n  * Urine protein \\\u003C 2+ on dipstick or \\\u003C 1.0 g per 24-hour urine collection\n  * Hepatic:\n  * Total bilirubin (TBil) ≤ 1.5 × upper limit of normal (ULN)\n  * AST and ALT ≤ 2.5 × ULN\n  * Serum albumin ≥ 28 g\u002FL\n  * Coagulation:\n  * International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN\n  * Cardiac:\n  * Left ventricular ejection fraction (LVEF) ≥ 50%\n  * Women of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to initiating study treatment. If the urine test is inconclusive, a serum test must confirm the result. Women of childbearing potential engaging in sexual activity with non-sterilized male partners must agree to use acceptable contraception from screening through 120 days after the last dose of study drug. The decision to discontinue contraception beyond this period should be discussed with the investigator. Periodic abstinence and the rhythm method are not acceptable.\n  * Women of childbearing potential are defined as those who have not undergone surgical sterilization (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) and have not been postmenopausal (defined as at least 12 consecutive months of amenorrhea without an alternative medical cause and FSH levels in the postmenopausal range).\n  * Highly effective contraception methods are those with a failure rate of \\\u003C1% per year when used consistently and correctly. In addition to barrier methods, hormonal contraception (e.g., oral contraceptives) must also be used.\n  * Willing and able to comply with scheduled visits, treatment procedures, laboratory tests, and other protocol requirements.\n\nExclusion Criteria:\n\n* • Known MSI-H or dMMR status.\n\n  * History of other malignancies within the past 3 years, except for those cured by local treatment, such as basal cell carcinoma, squamous cell carcinoma of the skin, superficial bladder cancer, or ductal carcinoma in situ of the breast.\n  * Prior immunotherapy, including immune checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies), immune agonists (e.g., ICOS, CD40, CD137, GITR, OX40), or immune cell-based therapies targeting tumor immunity.\n  * Prior adjuvant or neoadjuvant therapy targeting EGFR or VEGF\u002FVEGFR pathways (e.g., bevacizumab, cetuximab, panitumumab, aflibercept, regorafenib, or biosimilars).\n  * Active CNS metastases. Patients with previously treated brain metastases may be eligible if clinically stable for at least 2 weeks (from the first dose of study drug) and off corticosteroids for at least 3 days prior to treatment. Patients with untreated, asymptomatic brain metastases (no neurologic symptoms, no corticosteroids, and all lesions ≤ 1.5 cm in longest diameter) may enroll but require regular CNS monitoring.\n  * Known brainstem, meningeal, or spinal cord metastases or compression.\n  * Symptomatic or recurrently drained pleural effusion, pericardial effusion, or ascites.\n  * Prior systemic or local anti-tumor therapy for locally advanced rectal cancer, including curative surgery, chemotherapy, radiotherapy, immunotherapy, biologics, or small-molecule targeted therapy.\n  * Receipt of nonspecific immunomodulators (e.g., interleukins, interferons, thymic peptides, TNF) within 2 weeks prior to study treatment (except IL-11 for thrombocytopenia), or anti-tumor traditional Chinese medicine within 1 week prior to study treatment.\n  * Active autoimmune disease requiring systemic treatment within the past 2 years (e.g., with corticosteroids, immunosuppressants, or DMARDs). Replacement therapy (e.g., thyroid hormone, insulin, or physiologic corticosteroids for adrenal\u002Fpituitary insufficiency) is allowed.\n  * History of non-infectious pneumonitis requiring systemic corticosteroids, or current interstitial lung disease.\n  * History of bleeding disorders or coagulopathy; long-term anticoagulation (e.g., atrial fibrillation with CHADS2 score ≥ 2).\n  * Uncontrolled comorbidities including, but not limited to, decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer disease or gastritis, or psychiatric\u002Fsocial conditions impairing protocol compliance or informed consent.\n  * History of myocarditis, cardiomyopathy, or malignant arrhythmias; unstable angina, congestive heart failure, or vascular disease (e.g., aortic aneurysm requiring repair or DVT) requiring hospitalization within 12 months. Other cardiovascular conditions affecting drug safety (e.g., poorly controlled arrhythmias, myocardial infarction, or ischemia) are excluded.\n  * Within 6 months prior to study treatment: gastroesophageal varices, severe ulcers, unhealed wounds, GI perforation, fistulas, obstruction, intra-abdominal abscess, or acute GI bleeding.\n  * Within 6 months prior to treatment: arterial thromboembolism, venous thromboembolism (grade ≥3, NCI-CTCAE v5.0), TIA, stroke, hypertensive crisis, or hypertensive encephalopathy.\n  * COPD exacerbation within 1 month before study treatment; uncontrolled hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg despite oral medications).\n  * Active or prior history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea).\n  * Serious infections within 4 weeks before treatment, including those requiring hospitalization, sepsis, or severe pneumonia; active infection requiring systemic antibiotics within 10 days before treatment (excluding antiviral therapy for hepatitis B or C).\n  * Major surgery or significant trauma within 30 days prior to treatment; minor local surgery within 3 days (excluding PICC line placement).\n  * History of immunodeficiency; HIV antibody positivity; long-term use of systemic corticosteroids or immunosuppressants.\n  * Known active tuberculosis (TB) or suspected active TB not ruled out by clinical evaluation (e.g., sputum testing, chest imaging); known active syphilis.\n  * History of allogeneic organ or hematopoietic stem cell transplantation.\n  * Untreated active hepatitis B infection (HBsAg-positive with HBV DNA \\> 1,000 copies\u002FmL or \\>200 IU\u002FmL); patients with chronic hepatitis B must receive antiviral therapy during the study. Active hepatitis C (HCV antibody-positive with detectable HCV RNA) is also excluded.\n  * Receipt of a live vaccine within 30 days before treatment or planned live vaccination during the study.\n  * Known allergy to any component of the study drugs or history of serious hypersensitivity to monoclonal antibodies.\n  * Known psychiatric disorders, substance abuse, alcoholism, or drug dependence.\n  * Pregnant or breastfeeding women.\n  * Any condition, treatment, or laboratory abnormality that may interfere with study results, prevent full participation, or not be in the participant's best interest.\n  * Local or systemic disease caused by a benign tumor, or tumor-associated conditions causing high medical risk or survival uncertainty (e.g., leukemoid reaction with WBC \\> 20 × 10⁹\u002FL, cachexia with \\>10% weight loss within 3 months prior to screening, or BMI ≤ 18).\n  * Current evidence of significant gastrointestinal obstruction based on clinical or radiographic findings.\n  * History of bleeding disorders or coagulopathy; radiographic evidence of tumor encasing major vessels or showing necrosis\u002Fcavitation that, in the investigator's judgment, may pose bleeding risk; continuous anticoagulation within 10 days prior to first dose.\n  * Tumor invasion of critical organs or vessels (e.g., heart\u002Fpericardium, trachea, esophagus, aorta, or superior vena cava) with risk of complications such as fistulas (e.g., esophagotracheal, esophageal-pleural, or intestinal fistulas).\n  * Presence of free intraperitoneal gas not attributable to recent puncture or local surgical procedure.",{"count":92,"type":19},286,[50,94],"PHASE3","The current standard first-line treatment for metastatic colorectal cancer is chemotherapy combined with targeted therapy, yet the prognosis remains poor. Although combining immunotherapy, anti-angiogenic agents, and chemotherapy has shown some efficacy in MSS\u002FpMMR metastatic patients, progression-free survival (PFS) remains suboptimal. Radiotherapy-particularly high-dose radiotherapy-can enhance tumor antigen release and potentially improve the response of MSS\u002FpMMR colorectal cancer to PD-1 inhibitors. Tumor-draining lymph nodes (TDLNs) are key sites for PD-1-mediated anti-tumor activity, but radiation-induced damage and fibrosis may impair their immune function. Prior studies have reported a remarkable pathologic complete response (pCR) rate of 77.8% using node-sparing radiotherapy in locally advanced rectal cancer. This phase II\u002FIII study aims to evaluate whether node-sparing modified short-course radiotherapy combined with chemotherapy, bevacizumab, and PD-1 blockade can improve objective response rate (ORR) in phase II and progression-free survival (PFS) in phase III, together with treatment tolerance, and overall prognosis in patients with pMMR\u002FMSS metastatic colorectal cancer.",[25,77,97],"Metastatic Colorectal Cancer (CRC)","2025-08-04",{"date":100,"type":30},"2025-08-07",{"date":102,"type":30},"2025-05-01",{"date":82,"type":19},{"name":64,"class":37},{"id":106,"slug":107,"hasResults":11,"nctId":108,"briefTitle":109,"officialTitle":110,"acronym":4,"eligibilityCriteria":111,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":46,"enrollmentInfo":112,"targetDuration":4,"studyType":20,"phases":114,"briefSummary":115,"conditions":116,"keywords":4,"overallStatus":26,"whyStopped":4,"lastUpdateSubmitDate":98,"lastUpdatePostDateStruct":118,"startDateStruct":119,"completionDateStruct":120,"leadSponsor":121,"locationsCount":38},"100589747","phase-2-node-sparing-short-course-radiotherapy-sequential-chemotherapy-and-pd-1-inhibitor-for-midlow-pmmrmss-rectal-cancer-modifi-rc-ii-100589747","NCT06958432","Node-Sparing Short-Course Radiotherapy Sequential Chemotherapy and PD-1 Inhibitor for Mid\u002FLow pMMR\u002FMSS Rectal Cancer (MODIFI-RC-II)","Node-Sparing Short-Course Radiotherapy Plus Sequential Chemotherapy and PD-1 Inhibitor for Mid\u002FLow pMMR\u002FMSS Rectal Cancer: An Open-Label, Randomized, Prospective Phase II\u002FIII Trial (MODIFI-RC-II)","Inclusion Criteria:\n\n* • Voluntarily signs a written informed consent form.\n\n  * Aged between 18 and 75 years at the time of enrollment.\n  * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n  * Expected survival of more than 2 years.\n  * Histologically confirmed rectal adenocarcinoma.\n  * Tumor biopsy indicates proficient mismatch repair (pMMR), defined by positive immunohistochemical staining for MSH1, MSH2, MSH6, and PMS2, or molecular testing confirms microsatellite stability (MSS).\n  * Clinical stage T3-4N0M0 or TanyN+M0 based on the 8th edition of the AJCC TNM classification, as evaluated by high-resolution MRI ± endoscopic ultrasound\u002Ftransrectal ultrasonography, with the tumor located in the mid-to-lower rectum below the peritoneal reflection.\n  * Prior to enrollment, a qualified surgical attending physician must assess the patient's medical history and confirm eligibility for curative R0 resection.\n  * No prior systemic or local anti-tumor treatment for rectal cancer, including radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy.\n  * Agrees to provide tumor tissue and peripheral blood samples during screening and throughout the study for research purposes.\n  * Adequate organ function, defined as follows:\n  * Hematologic (without use of blood components or growth factors within 7 days prior to treatment initiation):\n  * Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹\u002FL\n  * Platelet count ≥ 100 × 10⁹\u002FL\n  * Hemoglobin ≥ 90 g\u002FL\n  * Renal:\n  * Calculated creatinine clearance (CrCl) ≥ 50 mL\u002Fmin using the Cockcroft-Gault formula:\n\nCrCl (mL\u002Fmin) = \\[(140 - age) × weight (kg) × 0.85 (if female)\\] \u002F (72 × serum creatinine \\[mg\u002FdL\\])\n\n* Urine protein \\\u003C 2+ on dipstick or \\\u003C 1.0 g per 24-hour collection\n* Hepatic:\n* Total bilirubin ≤ 1.5 × ULN\n* AST and ALT ≤ 2.5 × ULN\n* Serum albumin ≥ 28 g\u002FL\n* Coagulation:\n* INR and APTT ≤ 1.5 × ULN\n* Cardiac:\n* Left ventricular ejection fraction (LVEF) ≥ 50%\n* Women of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to initiating study treatment. If the urine test is inconclusive, a serum test must confirm the negative result. Women of childbearing potential who are sexually active with non-sterilized male partners must agree to use highly effective contraception from screening through 120 days after the last dose of study drug. The need for continued contraception beyond this period should be discussed with the investigator.\n* Women of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) and have not undergone menopause (defined as ≥12 months of amenorrhea without alternative medical cause, with FSH levels in the postmenopausal range).\n* Highly effective contraception methods are those with \\\u003C1% failure rate per year when used consistently and correctly (e.g., hormonal contraceptives). In addition to barrier methods, hormonal contraception is required. Periodic abstinence and the calendar method are not considered acceptable.\n* Willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study requirements.\n\nExclusion Criteria:\n\n* • Presence of suspected metastatic lesions or unresectable locally advanced disease, regardless of clinical stage.\n\n  * History of any other malignancy within 5 years prior to enrollment, excluding those considered cured by local therapy (e.g., basal cell carcinoma, squamous cell carcinoma of the skin, superficial bladder cancer, or ductal carcinoma in situ of the breast).\n  * Lesions initially staged as T1N0 eligible for local excision, or T2N0 suitable for sphincter-preserving surgery after multidisciplinary discussion.\n  * Evidence of acute conditions requiring emergency surgery, such as bowel obstruction, perforation, or gastrointestinal bleeding.\n  * Synchronous multiple primary rectal cancers.\n  * History of pelvic or abdominal radiotherapy.\n  * Inability to swallow tablets, malabsorption syndrome, or any condition affecting gastrointestinal absorption.\n  * Prior systemic or local anti-tumor therapy for locally advanced rectal cancer, including curative surgery, chemotherapy, radiotherapy, immunotherapy (e.g., immune checkpoint inhibitors, agonists, or cell-based therapies), biologics, or small-molecule targeted therapy.\n  * Use of nonspecific immunomodulatory treatments (e.g., interleukins, interferons, thymic peptides, tumor necrosis factor) within 2 weeks prior to study treatment (excluding IL-11 for thrombocytopenia), or use of herbal or traditional Chinese medicines with anti-tumor indications within 1 week prior to treatment.\n  * Active autoimmune disease requiring systemic treatment (e.g., with disease-modifying drugs, corticosteroids, or immunosuppressants) within the past 2 years. Replacement therapies (e.g., thyroid hormone, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic treatments.\n  * History of or current interstitial lung disease or non-infectious pneumonitis requiring systemic corticosteroid treatment.\n  * History of bleeding disorders or coagulopathy; patients requiring long-term anticoagulation (e.g., atrial fibrillation with CHADS2 score ≥ 2).\n  * Uncontrolled comorbidities, including but not limited to: decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe peptic ulcer or gastritis, or psychiatric\u002Fsocial conditions affecting compliance or consent.\n  * History of myocarditis, cardiomyopathy, or malignant arrhythmias; unstable angina, heart failure requiring hospitalization, or vascular disease (e.g., aortic aneurysm requiring repair or deep vein thrombosis) within 12 months prior to study treatment; other cardiac conditions impacting safety (e.g., poorly controlled arrhythmia, myocardial infarction, or ischemia).\n  * Within 6 months prior to treatment: history of gastroesophageal varices, severe ulcers, non-healed wounds, gastrointestinal perforation, fistulas, bowel obstruction, intra-abdominal abscess, or acute GI bleeding.\n  * Arterial thromboembolism, grade ≥3 venous thromboembolism (per NCI-CTCAE v5.0), transient ischemic attack, stroke, hypertensive crisis, or hypertensive encephalopathy within 6 months prior to study treatment.\n  * Acute exacerbation of COPD within 1 month prior to treatment; current hypertension not controlled to \\\u003C160\u002F100 mmHg despite antihypertensive medication.\n  * Active or prior inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) or chronic diarrhea.\n  * Severe infections within 4 weeks prior to treatment, including complications requiring hospitalization, sepsis, or severe pneumonia; active infections requiring systemic anti-infective therapy within 10 days prior to treatment (excluding antiviral therapy for HBV or HCV).\n  * Major surgery or serious trauma within 30 days prior to treatment; minor local surgery within 3 days (excluding PICC placement).\n  * History of immunodeficiency or HIV antibody positivity; long-term systemic corticosteroid or immunosuppressive therapy.\n  * Active tuberculosis or suspected TB not ruled out via clinical assessment (e.g., sputum test, chest X-ray); known active syphilis.\n  * History of allogeneic organ or hematopoietic stem cell transplantation.\n  * Untreated active hepatitis B (HBsAg-positive with HBV DNA \\> 1,000 copies\u002FmL or 200 IU\u002FmL); active hepatitis C (HCV antibody-positive with detectable HCV RNA).\n  * Receipt of a live vaccine within 30 days prior to treatment or planned live vaccination during the study.\n  * Known hypersensitivity to any component of the investigational drugs, or history of serious hypersensitivity reactions to monoclonal antibodies.\n  * Known history of psychiatric disorders, substance abuse, alcoholism, or drug addiction.\n  * Pregnant or breastfeeding women.\n  * Any disease, treatment, or abnormal laboratory finding that may interfere with study results, affect full study participation, or is not in the patient's best interest.\n  * Systemic or local disease caused by a benign tumor, or tumor-related complications\u002Fsymptoms that pose high medical risk or survival uncertainty (e.g., leukemoid reaction with WBC \\> 20 × 10⁹\u002FL, cachexia with \\>10% weight loss in 3 months prior to screening, or BMI ≤18).",{"count":113,"type":19},430,[50,94],"Most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) and respond poorly to PD-1 inhibitors. Radiotherapy can enhance tumor antigen release and improve responsiveness to PD-1 blockade in MSS\u002FpMMR rectal cancer. Tumor-draining lymph nodes (TDLNs) are critical sites for anti-tumor immune activation, but radiation-induced damage and fibrosis may impair lymphatic drainage and immune responses. Previous studies have reported a remarkable pathologic complete response (pCR) rate of 77.8% using node-sparing radiotherapy in locally advanced rectal cancer. This study aims to evaluate whether node-sparing short-course radiotherapy followed by sequential chemotherapy and PD-1 blockade can improve complete response rate in the phase II part and event-free survival in phase III part, together with sphincter preservation, treatment tolerance, and prognosis in patients with mid-low pMMR\u002FMSS rectal cancer.",[117,54,25,77],"Rectal Cancer",{"date":100,"type":30},{"date":102,"type":30},{"date":82,"type":19},{"name":64,"class":37},{"id":123,"slug":124,"hasResults":11,"nctId":125,"briefTitle":126,"officialTitle":127,"acronym":4,"eligibilityCriteria":128,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":46,"enrollmentInfo":129,"targetDuration":4,"studyType":20,"phases":131,"briefSummary":132,"conditions":133,"keywords":4,"overallStatus":135,"whyStopped":4,"lastUpdateSubmitDate":136,"lastUpdatePostDateStruct":137,"startDateStruct":139,"completionDateStruct":141,"leadSponsor":142,"locationsCount":38},"100591435","phase-2-node-sparing-short-course-radiotherapy-plus-first-line-therapy-and-pd-1-inhibitor-in-unresectablemetastastic-pmmrmss-gastric-cancer-modifi-gc-100591435","NCT06980389","Node-Sparing Short-Course Radiotherapy Plus First-Line Therapy and PD-1 Inhibitor in Unresectable\u002FMetastastic pMMR\u002FMSS Gastric Cancer (MODIFI-GC)","Node-Sparing Short-Course Radiotherapy Followed by First-Line Therapy Plus PD-1 Inhibitor in Unresectable Locally Advanced or Metastatic pMMR\u002FMSS Gastric Cancer: A Prospective, Randomized, Controlled Phase II Trial (MODIFI-GC)","Inclusion Criteria:\n\n* Voluntarily signs a written informed consent form.\n\n  * Aged between 18 and 75 years at the time of enrollment.\n  * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n  * Expected survival of more than 3 months.\n  * At least one measurable lesion as defined by RECIST 1.1.\n  * Histologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction.\n  * Tumor biopsy indicates proficient mismatch repair (pMMR) based on positive immunohistochemical staining for MSH1, MSH2, MSH6, and PMS2, or microsatellite stability (MSS) by genetic testing.\n  * No prior systemic anti-tumor therapy before study treatment, including radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy.\n  * Agrees to provide tumor tissue and peripheral blood samples during screening and throughout the study for research purposes.\n  * Adequate organ function as defined below:\n  * Hematologic (without blood transfusion or hematopoietic growth factor support within 7 days prior to treatment):\n  * Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹\u002FL\n  * Platelet count ≥ 100 × 10⁹\u002FL\n  * Hemoglobin ≥ 90 g\u002FL\n  * Renal:\n  * Calculated creatinine clearance (CrCl) ≥ 50 mL\u002Fmin using the Cockcroft-Gault formula:\n\nCrCl = \\[(140 - age) × weight (kg) × 0.85 (if female)\\] \u002F \\[72 × serum creatinine (mg\u002FdL)\\]\n\n* Urine protein \\\u003C 2+ by dipstick or \\\u003C 1.0 g\u002F24 h\n* Hepatic:\n* Total bilirubin (TBil) ≤ 1.5 × upper limit of normal (ULN)\n* AST and ALT ≤ 2.5 × ULN\n* Serum albumin ≥ 28 g\u002FL\n* Coagulation:\n* INR and APTT ≤ 1.5 × ULN\n* Cardiac:\n* Left ventricular ejection fraction (LVEF) ≥ 50%\n* Women of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to study treatment. If urine test is inconclusive, a serum test result shall prevail. Women of childbearing potential who are sexually active with non-sterilized male partners must agree to use an acceptable method of contraception from screening through 120 days after the last dose of study drug. Whether to discontinue contraception after this period should be discussed with the investigator. Periodic abstinence and calendar methods are not acceptable.\n* Women of childbearing potential are defined as those who have not undergone surgical sterilization (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) and who are not postmenopausal (defined as ≥12 months of amenorrhea without alternative medical cause and with serum FSH levels in the postmenopausal range).\n* Highly effective contraception methods are those with a failure rate \\\u003C1% per year when used consistently and correctly. In addition to barrier methods, hormonal contraception (e.g., oral contraceptives) must also be used.\n* Willing and able to comply with all scheduled visits, treatment plans, laboratory tests, and other study requirements.\n\nExclusion Criteria:\n\n* • Radiotherapy within 4 weeks prior to enrollment or radionuclide therapy within 8 weeks, except for palliative radiotherapy to bone metastases.\n\n  * History of other malignancies within 5 years prior to enrollment, except for those considered cured by local therapy, such as basal cell carcinoma, squamous cell carcinoma of the skin, superficial bladder cancer, or ductal carcinoma in situ of the breast.\n  * Gastrointestinal perforation and\u002For fistula within 6 months prior to enrollment.\n  * Clinically significant bowel obstruction.\n  * Symptomatic central nervous system (CNS) metastases.\n  * Diagnosis of HER2-positive gastric or gastroesophageal junction adenocarcinoma.\n  * Inability to swallow oral medications, malabsorption syndrome, or any other condition affecting gastrointestinal absorption.\n  * Prior systemic or local anti-tumor therapy for gastric cancer, including curative surgery, chemotherapy, radiotherapy, immunotherapy (e.g., immune checkpoint inhibitors, agonists, or cell therapy), biologics, or small-molecule targeted agents.\n  * Receipt of nonspecific immunomodulatory agents (e.g., interleukins, interferons, thymic peptides, tumor necrosis factor) within 2 weeks prior to study treatment (excluding IL-11 for thrombocytopenia); use of anti-tumor traditional Chinese medicine within 1 week prior to study treatment.\n  * Active autoimmune disease requiring systemic therapy within the past 2 years (e.g., corticosteroids, immunosuppressants, DMARDs). Replacement therapy (e.g., thyroid hormone, insulin, or physiologic corticosteroids for adrenal\u002Fpituitary insufficiency) is permitted.\n  * History of or current interstitial lung disease or non-infectious pneumonitis requiring systemic corticosteroids.\n  * History of significant bleeding disorders or coagulopathy; current or prior long-term anticoagulation (e.g., atrial fibrillation with CHADS2 score ≥ 2).\n  * Uncontrolled comorbidities including, but not limited to, decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer or gastritis, or psychiatric\u002Fsocial conditions interfering with protocol compliance or informed consent.\n  * History of myocarditis, cardiomyopathy, or malignant arrhythmia; unstable angina, heart failure requiring hospitalization, or vascular disease (e.g., aortic aneurysm requiring repair or DVT) within 12 months before treatment; other cardiac conditions that may interfere with safety evaluation, such as poorly controlled arrhythmias, myocardial infarction, or ischemia.\n  * Within 6 months prior to treatment: gastroesophageal varices, severe ulcers, unhealed wounds, GI perforation, fistula, intestinal obstruction, intra-abdominal abscess, or acute GI bleeding.\n  * Arterial thromboembolism, grade ≥3 venous thromboembolism (per NCI CTCAE v5.0), TIA, stroke, hypertensive crisis, or hypertensive encephalopathy within 6 months before treatment.\n  * Acute exacerbation of COPD within 1 month prior to treatment; uncontrolled hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg despite oral therapy).\n  * Active or prior history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) or chronic diarrhea.\n  * Serious infection within 4 weeks prior to treatment, including those requiring hospitalization, sepsis, or severe pneumonia; active systemic infection requiring anti-infective therapy within 10 days before treatment (excluding antiviral therapy for HBV or HCV).\n  * Major surgery or significant trauma within 30 days prior to treatment; minor local surgery within 3 days prior (excluding central venous catheter placement via peripheral vein).\n  * History of immunodeficiency; HIV antibody positive; long-term use of systemic corticosteroids or immunosuppressants.\n  * Known active tuberculosis (TB), or suspected active TB not ruled out by clinical assessment (e.g., sputum testing, chest imaging); known active syphilis.\n  * History of allogeneic organ or hematopoietic stem cell transplantation.\n  * Untreated active hepatitis B infection (HBsAg positive and HBV DNA \\> 1,000 copies\u002FmL or 200 IU\u002FmL); patients with HBV must receive antiviral therapy during the study. Active hepatitis C infection (HCV antibody positive with detectable HCV RNA) is also excluded.\n  * Receipt of a live vaccine within 30 days prior to treatment or planned during the study period.\n  * Known allergy to any component of study drugs or history of severe hypersensitivity to monoclonal antibodies.\n  * Known history of psychiatric disorders, substance abuse, alcoholism, or drug addiction.\n  * Pregnant or breastfeeding women.\n  * Any condition, treatment, or abnormal laboratory findings that may confound study results, interfere with study participation, or not be in the best interest of the participant.\n  * Local or systemic disease caused by benign tumors, or tumor-related complications with high medical risk or uncertain prognosis (e.g., leukemoid reaction with WBC \\> 20 × 10⁹\u002FL, cachexia with \\>10% weight loss in 3 months before screening, or BMI ≤ 18).",{"count":130,"type":19},176,[50],"For patients with unresectable locally advanced or metastatic gastric cancer, systemic anti-tumor therapy remains the mainstay of treatment. Combining chemotherapy with immune checkpoint inhibitors has gradually become the standard first-line treatment for advanced gastric cancer. Radiotherapy can enhance the release of tumor-associated antigens, thereby improving the responsiveness of MSS\u002FpMMR tumors to PD-1 inhibitors. Tumor-draining lymph nodes (TDLNs) are key sites for the anti-tumor activity of PD-1 blockade; however, radiation-induced damage and fibrosis may impair lymphatic drainage and local immune responses. Previous studies have suggested that irradiation of the primary tumor combined with immune checkpoint blockade can produce an abscopal effect, mediating regression of distant metastases. This study aims to evaluate whether node-sparing modified short-course radiotherapy followed by chemotherapy and PD-1 blockade can improve 2-year progression-free survival (PFS) in patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.",[25,77,134],"Metastatic Gastric Carcinoma","NOT_YET_RECRUITING","2025-05-12",{"date":138,"type":30},"2025-05-20",{"date":140,"type":19},"2025-05-31",{"date":34,"type":19},{"name":64,"class":37},{"id":144,"slug":145,"hasResults":11,"nctId":146,"briefTitle":147,"officialTitle":148,"acronym":4,"eligibilityCriteria":149,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":46,"enrollmentInfo":150,"targetDuration":4,"studyType":20,"phases":152,"briefSummary":153,"conditions":154,"keywords":4,"overallStatus":26,"whyStopped":4,"lastUpdateSubmitDate":155,"lastUpdatePostDateStruct":156,"startDateStruct":158,"completionDateStruct":160,"leadSponsor":161,"locationsCount":38},"100587050","phase-2-modified-long-course-radiotherapy-followed-by-chemotherapy-and-pd-1-inhibitor-for-msspmmr-high-risk-midlow-larc-modifi-rc-i-100587050","NCT06923345","Modified Long-Course Radiotherapy Followed by Chemotherapy and PD-1 Inhibitor for MSS\u002FpMMR High-risk Mid\u002FLow LARC (MODIFI-RC-I)","Modified Long-Course Radiotherapy (Reduced vs. Conventional CTV), Sequential Chemotherapy and PD-1 Inhibitor in Locally Advanced, MSS, Mid-Low Rectal Cancer: An Open-Label, Two-Arm, Randomized, Prospective Phase II Clinical Trial (MODIFI-RC-I)","Inclusion Criteria:\n\n* Voluntarily signs a written informed consent form.\n* Aged between 18 and 75 years at enrollment.\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n* Expected survival of more than 2 years.\n* Histologically confirmed rectal adenocarcinoma.\n* Tumor biopsy immunohistochemistry indicating pMMR (MSH1, MSH2, MSH6, and PMS2 all positive) or genetic testing confirming MSS.\n* According to the 8th edition of the AJCC TNM classification, high-resolution MRI ± endorectal ultrasound confirms clinical staging as cT3-4NanyM0 or cTxN+M0 (stage II-III rectal cancer). MRI confirms the tumor is located below the peritoneal reflection without lateral lymph node metastasis.\n* Before study enrollment, a responsible surgical attending physician must evaluate the patient's medical history to confirm eligibility for R0 resection with curative intent.\n* No prior systemic or local anti-tumor treatment for rectal cancer, including radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy.\n* Willing to provide tumor tissue and peripheral blood samples for research purposes during screening and throughout the study.\n* Adequate organ function:\n* Hematology (without recent blood transfusions or growth factor support within 7 days before treatment):\n\n  * Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹\u002FL (1,500\u002Fmm³)\n  * Platelet count ≥ 100 × 10⁹\u002FL (100,000\u002Fmm³)\n  * Hemoglobin ≥ 90 g\u002FL\n* Renal function:\n\n  * Estimated creatinine clearance (CrCl) ≥ 50 mL\u002Fmin (calculated using the Cockcroft-Gault formula)\n  * Urine protein \\\u003C 2+ or 24-hour urine protein quantification \\\u003C 1.0 g\n* Liver function:\n\n  * Total bilirubin (TBil) ≤ 1.5 × upper limit of normal (ULN)\n  * AST and ALT ≤ 2.5 × ULN\n  * Serum albumin (ALB) ≥ 28 g\u002FL\n* Coagulation function:\n\n  o INR and APTT ≤ 1.5 × ULN\n* Cardiac function:\n\n  o Left ventricular ejection fraction (LVEF) ≥ 50%\n* Female participants of childbearing potential must have a negative urine or serum pregnancy test within 3 days before starting study treatment. If a urine pregnancy test result is unclear, a confirmatory serum pregnancy test must be conducted. Participants with childbearing potential who engage in sexual activity with non-sterilized male partners must use highly effective contraception from screening until 120 days after the last dose of study treatment. The use of periodic abstinence and fertility awareness methods is not considered acceptable contraception.\n* Definition of females of childbearing potential (FCBP): Women who have not undergone surgical sterilization (bilateral tubal ligation, bilateral oophorectomy, or total hysterectomy) or who have not been naturally postmenopausal for at least 12 consecutive months (confirmed by FSH levels within the postmenopausal range).\n* Highly effective contraception methods: Must have a failure rate of \\\u003C1% per year when used consistently and correctly. In addition to barrier methods, FCBP must use an additional hormonal contraceptive method (e.g., oral contraceptives).\n* Participants must be willing and able to comply with study visit schedules, treatment plans, laboratory tests, and other study-related requirements.\n\nExclusion Criteria:\n\n* Presence of suspected metastatic lesions or locally advanced unresectable disease, regardless of disease stage.\n* Diagnosis of other malignancies within the past five years, except for patients with malignancies cured through local treatment (e.g., basal or squamous cell skin cancer, superficial bladder cancer, ductal carcinoma in situ of the breast).\n* Concurrent enrollment in another clinical study, unless it is an observational, non-interventional study or a follow-up phase of an interventional study.\n* Presence of intestinal obstruction, perforation, or bleeding requiring emergency surgery.\n* Multiple primary rectal cancers.\n* History of pelvic or abdominal radiotherapy.\n* Inability to swallow tablets, malabsorption syndrome, or any condition affecting gastrointestinal absorption.\n* Prior systemic or local anti-tumor treatment for locally advanced rectal cancer, including radical surgery, chemotherapy, radiotherapy, immunotherapy (e.g., immune checkpoint inhibitors, immune cell therapy), biological agents, or targeted therapy.\n* Use of nonspecific immunomodulatory treatment (e.g., interleukins, interferons, thymosin, TNF) within two weeks before study treatment (excluding IL-11 for thrombocytopenia); use of traditional Chinese medicine with anti-tumor indications within one week before study treatment.\n* Active autoimmune disease requiring systemic treatment in the past two years, except for replacement therapy (e.g., thyroid hormone, insulin, corticosteroids for adrenal\u002Fpituitary insufficiency).\n* History of non-infectious pneumonitis requiring systemic glucocorticoid therapy or interstitial lung disease.\n* History of severe bleeding tendency, coagulopathy, or long-term anticoagulation therapy (e.g., atrial fibrillation with CHADS2 score ≥2).\n* Uncontrolled comorbidities, including but not limited to decompensated liver cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer disease, or psychiatric\u002Fsocial conditions limiting compliance.\n* History of myocarditis, cardiomyopathy, malignant arrhythmias; hospitalization for unstable angina, congestive heart failure, or vascular diseases (e.g., aortic aneurysm requiring surgery) within 12 months before study treatment.\n* History of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, chronic diarrhea).\n* Severe infection within four weeks before study treatment, including sepsis or severe pneumonia requiring hospitalization; active infection requiring systemic therapy within ten days before study treatment (excluding antiviral therapy for HBV or HCV).\n* Major surgery or severe trauma within 30 days before study treatment; minor surgery (excluding peripheral venous catheterization) within three days before study treatment.\n* Immunodeficiency history, positive HIV test, or long-term use of systemic corticosteroids or immunosuppressants.\n* Active tuberculosis or suspected TB requiring clinical exclusion; known active syphilis infection.\n* History of allogeneic organ or hematopoietic stem cell transplantation.\n* Untreated active HBV infection (HBsAg-positive with HBV-DNA \\> 1000 copies\u002Fml or 200 IU\u002Fml); active HCV infection (HCV antibody-positive with detectable HCV-RNA).\n* Live vaccine administration within 30 days before study treatment or planned during the study period.\n* Known hypersensitivity to any study drug component or history of severe hypersensitivity reactions to monoclonal antibodies.\n* History of psychiatric disorders, substance abuse, alcohol dependence, or drug addiction.\n* Pregnant or breastfeeding women.\n* Any disease, treatment, or laboratory abnormality that may confound study results, interfere with full study participation, or is not in the participant's best interest.\n* Non-malignant or tumor-related systemic diseases or symptoms causing high medical risk or uncertainty in survival assessment.",{"count":151,"type":19},80,[50],"The goal of this clinical trial is to evaluate whether a total neoadjuvant therapy (TNT) regimen combining long-course chemoradiotherapy, sequential chemotherapy, and PD-1 inhibitor can improve response rates, enhance tolerability, and improve prognosis in patients with locally advanced, microsatellite-stable (MSS) rectal cancer.\n\nThe main questions it aims to answer are:\n\nDoes this TNT approach improve complete response (CR) rates?\n\nHow does selective reduction of clinical target volume (CTV) to S2\u002FS3 level compare with conventional CTV irradiation in terms of efficacy and safety?\n\nResearchers will compare a selective CTV reduction group and a conventional CTV irradiation group to assess differences in treatment outcomes, including complete response, tumor regression grading (TRG), organ preservation, R0 resection rates, and long-term survival.\n\nParticipants will:\n\nReceive long-course chemoradiotherapy with either conventional or reduced CTV irradiation.\n\nUndergo sequential chemotherapy.\n\nReceive PD-1 inhibitor treatment.\n\nBe monitored for safety, tumor regression, and long-term survival outcomes.",[117,54,25,77],"2025-04-15",{"date":157,"type":30},"2025-04-18",{"date":159,"type":30},"2025-03-31",{"date":34,"type":19},{"name":64,"class":37},{"id":163,"slug":164,"hasResults":11,"nctId":165,"briefTitle":166,"officialTitle":166,"acronym":167,"eligibilityCriteria":168,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":169,"targetDuration":4,"studyType":171,"phases":4,"briefSummary":172,"conditions":173,"keywords":178,"overallStatus":26,"whyStopped":4,"lastUpdateSubmitDate":189,"lastUpdatePostDateStruct":190,"startDateStruct":192,"completionDateStruct":194,"leadSponsor":196,"locationsCount":199},"100564959","a-prospective-real-world-evidence-study-prowes-for-concordance-rate-of-blood-based-3d-genome-conformation-mapping-episwitch-cirt-to-identify-likelihood-of-response-and-actual-response-rates-to-pd-l-1-checkpoint-inhibitors-across-multiple-oncological-indications-100564959","NCT06635954","A Prospective Real World Evidence Study (PROWES) for Concordance Rate of Blood-based 3D Genome Conformation Mapping (Episwitch CiRT®) to Identify Likelihood of Response and Actual Response Rates to PD-(L)-1 Checkpoint Inhibitors Across Multiple Oncological Indications.","PROWES","Inclusion Criteria:\n\n1. 18 years of age or older\n2. Stage III or IV cancer\n3. Selected by their healthcare provider to receive the Episwitch CiRT® test according to the current evidence-based schedule (per protocol) as part of their standard of practice.\n4. ECOG performance status ≤ 2\n5. Clinically eligible for ICI therapy\n6. Able to read, understand and provide written informed consent.\n7. Willing and able to comply with the study requirements\n\nExclusion Criteria:\n\n1. Pregnant or breastfeeding\n2. History of bone marrow or organ transplant\n3. Contra indication for receiving Immune Check Point inhibitor.",{"count":170,"type":19},2000,"OBSERVATIONAL","The purpose of this research is to test whether a blood-based 3D genome conformation mapping test called the Episwitch CiRT® can help to identify likelihood of response to PD-(L)-1 checkpoint inhibitors (a class of cancer drugs) across multiple oncological indications by comparing the results to actual treatment responses for cancer patients.",[174,175,176,177,25],"Cancer","Immunotherapy","PD-1","PD-L1",[179,180,181,182,183,184,185,186,187,188,176,177],"immunotherapy","immune checkpoint inhibitor","ICI therapy","ICI","Immune Checkpoint Inhibitor therapy","Episwitch","Episwitch CiRT","Immune Related Adverse Event","IRAE","cancer","2025-03-12",{"date":191,"type":30},"2025-03-17",{"date":193,"type":30},"2024-05-14",{"date":195,"type":19},"2027-05-14",{"name":197,"class":198},"Oxford Biodynamics Inc.","INDUSTRY",3]