[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"ras-mutation\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:ras-mutation":28},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,11,0,[8,46,83,113,148,186,214,244,268,290,314],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":13,"conditions":25,"keywords":29,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":34,"lastUpdatePostDateStruct":35,"startDateStruct":38,"completionDateStruct":40,"leadSponsor":42,"locationsCount":45},"100645104","phase-1-a-study-of-gfh276-combined-with-cetuximab-or-chemotherapy-in-participants-with-solid-tumors-and-pancreatic-ductal-adenocarcinoma-pdac-harboring-ras-mutation-100645104",false,"NCT07678593","A Study of GFH276 Combined With Cetuximab or Chemotherapy in Participants With Solid Tumors and Pancreatic Ductal Adenocarcinoma (PDAC) Harboring RAS Mutation","A Multi-center, Open-label Phase Ib\u002FII Study Exploring the Safety\u002FTolerability, Pharmacokinetics, and Efficacy of GFH276 in Combination With Cetuximab or Chemotherapy in the Treatment of Patients With Advanced Solid Tumors and Pancreatic Ductal Adenocarcinoma (PDAC) Harboring RAS Mutation","Inclusion Criteria:\n\n1. Age ≥ 18 years\n2. Histologically or cytologically confirmed locally advanced or metastatic solid tumor and PDAC with RAS mutation or KRAS amplification\n3. At least one measurable lesion according to RECIST v1.1\n4. ECOG performance status 0 or 1\n5. Life expectancy \\> 3 months\n6. Adequate organ function\n7. Willing to provide written informed consent\n8. Fertile participants must use effective contraception\n\nExclusion Criteria:\n\n1. Other active malignancy within 3 years\n2. Symptomatic brain metastases, leptomeningeal disease, spinal cord compression, or primary brain tumor\n3. History of active clinically significant cardiovascular dysfunction\n4. For participants with known concomitant second oncodriver for PDAC or for solid tumors.\n5. With active infection (HIV, HBV, HCV, syphilis)\n6. The presence of clinical or radiological evidence of intestinal obstruction.\n7. Prior anticancer therapy within 28 days or 5 half-lives\n8. Diagnosis of deep vein thrombosis or pulmonary embolism within 3 months\n9. Hypersensitivity to study drugs, or inability to swallow tablets or comply with study procedures.\n10. History of central nervous system (CNS)disease\n11. Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonia that requires treatment.\n12. With uncontrollable or symptomatic pleural effusion, ascites, or pericardial effusion.","ALL","18 Years",{"count":19,"type":20},222,"ESTIMATED","INTERVENTIONAL",[23,24],"PHASE1","PHASE2",[26,27,28],"Advanced Solid Tumors Cancer","Pancreatic Ductal Adenocarcinoma","RAS Mutation",[30,31,28,32],"GFH276","PDAC","solid tumors","NOT_YET_RECRUITING","2026-06-24",{"date":36,"type":37},"2026-07-01","ACTUAL",{"date":39,"type":20},"2026-09",{"date":41,"type":20},"2028-09",{"name":43,"class":44},"Genfleet Therapeutics (Shanghai) Inc.","INDUSTRY",3,{"id":47,"slug":48,"hasResults":11,"nctId":49,"briefTitle":50,"officialTitle":51,"acronym":4,"eligibilityCriteria":52,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":53,"targetDuration":4,"studyType":21,"phases":55,"briefSummary":56,"conditions":57,"keywords":63,"overallStatus":73,"whyStopped":4,"lastUpdateSubmitDate":74,"lastUpdatePostDateStruct":75,"startDateStruct":77,"completionDateStruct":79,"leadSponsor":81,"locationsCount":45},"100414594","phase-1-a-trial-of-rsc-1255-for-treatment-of-patients-with-advanced-malignancies-100414594","NCT04678648","A Trial of RSC-1255 for Treatment of Patients With Advanced Malignancies","A Phase Ia\u002FIb, Open Label, Multi-center, Non-randomized Dose Escalation and Dose Expansion Study of RSC-1255 Alone or in Combination With Hydroxychloroquine in Patients With Advanced Solid Tumor Malignancies","Inclusion Criteria (Key Factors):\n\n1. Has pathologically confirmed advanced or metastatic malignancy characterized by one or more of the following:\n\n   * Participant is intolerant of existing therapy(ies) known to provide clinical benefit for their condition\n   * Malignancy is refractory to existing therapy(ies) known to potentially provide clinical benefit\n   * Malignancy has progressed on standard therapy\n2. Has evaluable or measurable tumor(s) in dose-escalation by standard radiological and\u002For laboratory assessments as applicable to their malignancy.\n3. Has adequate performance status (PS): Eastern Co-operative Oncology Group (ECOG).\n4. Is age ≥ 18 years.\n5. Has either tissue agnostic tumors and documented RAS mutations or with glioblastoma with or without mutation in RAS\n\nExclusion Criteria (Key Factors):\n\n1. Participants receiving cancer therapy at the time of enrollment.\n2. Any clinically significant disease or condition affecting a major organ system.\n3. Significant cardiovascular disease or electrocardiogram (ECG) abnormalities.\n4. Known Gilbert's disease.\n5. Has had a previous (within 2 years) or has a current malignancy other than the target cancer.\n6. Intermittent hypokalemia\n7. Grade 1 or higher nausea, vomiting, diarrhea at baseline due to underlying disease",{"count":54,"type":20},134,[23],"RSC-101 is a Phase 1a\u002F1b clinical trial of RSC-1255 in adult study participants with advanced solid tumor malignancies who are intolerant of existing therapies known to provide clinical benefit, have disease that has progressed after standard therapy, or have previously failed other therapies. The study has two phases. The purpose of Phase 1a (Dose Escalation) is to confirm the appropriate treatment dose and Phase 1b (Dose Expansion) is to characterize the safety and efficacy of RSC-1255.",[58,28,59,60,61,62],"Advanced Malignant Solid Neoplasm","Lung Cancer","Colon Cancer","Glioblastoma","Pancreatic Cancer",[64,65,66,67,68,69,61,70,71,72],"Malignancy","Cancer","Refractory","RAS mutation","Lung","Colon","RSC-1255","Progression","Pancreatic","RECRUITING","2026-06-22",{"date":76,"type":37},"2026-06-23",{"date":78,"type":37},"2021-03-03",{"date":80,"type":20},"2027-01-30",{"name":82,"class":44},"RasCal Therapeutics, Inc.",{"id":84,"slug":85,"hasResults":11,"nctId":86,"briefTitle":87,"officialTitle":88,"acronym":4,"eligibilityCriteria":89,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":90,"targetDuration":4,"studyType":21,"phases":92,"briefSummary":93,"conditions":94,"keywords":96,"overallStatus":73,"whyStopped":4,"lastUpdateSubmitDate":104,"lastUpdatePostDateStruct":105,"startDateStruct":107,"completionDateStruct":109,"leadSponsor":111,"locationsCount":45},"100612353","phase-1-evaluation-of-ras-inhibitor-treatment-in-participants-with-advanced-or-metastatic-solid-tumors-harboring-ras-mutations-100612353","NCT07252479","Evaluation of RAS Inhibitor Treatment in Participants With Advanced or Metastatic Solid Tumors Harboring RAS Mutations","A Multi-center, Open-label, Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of AN9025 in Participants With Advanced or Metastatic Solid Tumors Harboring RAS Mutations","Inclusion Criteria:\n\n1. Aged ≥18 years old at the time of informed consent.\n2. Able to provide informed consent voluntarily before any study-related activities and according to local guidelines.\n3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.\n4. Have an estimated life expectancy ≥ 12 weeks, in the judgment of the Investigator.\n5. Have histological or cytological evidence of a diagnosis of cancer that is advanced and\u002For metastatic with progression after treatment with available standard therapies.\n6. Documentation of KRAS\u002FNRAS\u002FHRAS mutation determined by validated local testing of tumor tissue or circulating free DNA (cfDNA) in a certified laboratory.\n\n   Note: Participants with melanoma who have documented loss-of-function NF1 mutation and wild type KRAS\u002FNRAS\u002FHRAS\u002FBRAF are also eligible for the backfill of Part 1 cohorts QD, QW.\n7. Have consented to provide archival tumor tissue collected within 5 years or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.\n8. Part 1 Dose-Escalation and Part 2 Food Effect Assessment: cancers including, but not limited to:\n\n   1. Pancreatic ductal adenocarcinoma (PDAC)\n   2. Colorectal cancer (CRC)\n   3. Non-small cell lung cancer (NSCLC)\n   4. Cutaneous melanoma\n   5. Biliary tract cancer (BTC)\n9. Part 3 Dose-Expansion:\n\n   Cohort 3A: RAS-mutated solid tumors (2L\u002F3L)\n   1. Histologically or cytologically confirmed advanced or metastatic disease\n   2. Participants must not have tumors previously tested positive for targetable oncogenic driver mutations including Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK), B-Rapidly Accelerated Fibrosarcoma (BRAF), RET, and ROS1\n   3. Participants must have received 1 or 2 prior lines of systemic therapy which include prior immune checkpoint inhibitor and platinum chemotherapy administered either concurrently or sequentially, and have not received docetaxel previously\n   4. Participants must be refractory to anti-PD-1\u002FPD-L1 therapy.\n   5. Adjuvant therapy or multimodal therapy with curative intent is considered prior therapy if disease progression occurred or treatment completion was within 6 months of first dose of AN9025.\n   6. Participants must not have tumors previously tested positive for Class I BRAF mutations i.e. V600X.\n10. Have adequate organ functions prior to enrollment:\n\n    1. ANC: \\>= 1.5 x 10\\^9\u002FL\n    2. Platelets: \\>= 100x 10\\^9\u002FL\n    3. Hemoglobin: \\>= 9.0 g\u002FdL\n    4. AST and ALT: \\\u003C= 2.5 x Upper Limit of Normal (ULN) or ,+ x ULN if liver metastases are present\n    5. Total bilirubin: \\\u003C= 1.5 x ULN\n    6. Creatinine clearance (CrCl): CrCl \\>= 50 ml\u002Fmin as determined by Cockcroft-Gaulat formula\n    7. International Normalized Ratio (INR) or prothrombin (PT) time or activated partial thromboplastin time (aPTT): PT or aPTT \\\u003C= 1.5 x ULN or INR \\\u003C 1.5\n11. Have discontinued all previous treatments for cancer with resolution of any adverse events (AEs) to ≤ Grade 1 (except for alopecia, and endocrinopathies that are managed with replacement therapy), and all clinically significant toxicities from prior locoregional therapy, surgery, radiotherapy, or systemic anticancer therapy to ≤ Grade 1 prior to enrollment.\n12. Corrected QT interval (QTc) ≤ 470 msec for females and ≤ 450 msec for males per the Fridericia's Formula (QTcF).\n13. Able to swallow oral medication and comply with study requirements.\n14. Left ventricular ejection fraction (LVEF) greater than 50% on echocardiography or multiple gated acquisition (MUGA) scan.\n15. Fertile men and women of childbearing potential must agree to use an effective method of birth control from providing signed consent and for 180 days after the last study treatment administration. Women of childbearing potential include pre-menopausal women and women within the first 2 years of the onset of menopause. Women of childbearing potential must have a negative pregnancy test ≤ 14 days prior to the first dose of the study treatment.\n\nExclusion Criteria:\n\nParticipants meeting any of the following criteria will not be eligible for participation in the study.\n\n1. Are currently enrolled in a clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.\n2. Have tumors previously tested positive for Class I BRAF mutations i.e. V600X.\n3. Prior treatment with a pan-RAS(ON) inhibitor, ) except for participants enrolled in the backfill cohorts who have experienced radiological or clinical disease progression on prior pan-RAS(ON) inhibitor therapy.\n4. Gastrointestinal conditions that may interfere with drug absorption (e.g., malabsorption syndrome, chronic nausea\u002Fvomiting, active inflammatory bowel disease).\n5. Have a serious concomitant systemic disorder that, in the judgment of the Investigator, would compromise the participant's ability to adhere to the protocol, such as the following:\n\n   1. Known human immunodeficiency virus (HIV) infection per HIV 1 and\u002For 2 antibodies.\n   2. Participants with evidence of active Hepatitis B or Hepatitis C infections (positive for Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody)\n   3. Active tuberculosis, fungal infection\n   4. Active infection requiring intravenous antibiotic therapy. Use of oral antibiotics for minor infections (e.g., uncomplicated UTI or URI) is permitted if clinically stable, at the Investigator's discretion\n6. The participant has a serious pre-existing medical condition(s) that, in the judgment of the Investigator, would preclude participation in this study, including interstitial lung disease (ILD), severe dyspnea at rest, or requiring oxygen therapy.\n7. Prior or second concurrent primary malignancies that, in the judgment of the Investigator, may affect the interpretation of results. Participants with carcinoma in situ of any origin and participants with prior malignancies who are in remission and whose likelihood of recurrence is very low (such as basal cell carcinoma), as judged by the Investigator, or malignancies that don't need treatment (i.e., small renal cell carcinoma \\[RCC\\] and localized prostate cancer) are eligible for this study.\n8. Moderate or severe cardiovascular disease, such as the following:\n\n   1. congestive heart failure\n   2. New York Heart Association Class III\u002FIV heart disease\n   3. unstable angina pectoris\n   4. myocardial infarction or cardiovascular event within the last 6 months before enrollment\n   5. valvulopathy that is severe, moderate, or deemed clinically significant\n   6. arrhythmias that are symptomatic or require treatment (not including Participants with rate-controlled supraventricular tachycardia)\n   7. a history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT syndrome)\n   8. require the use of concomitant medications that prolong the QT\u002FQTc interval\n9. Have symptomatic central nervous system (CNS) malignancy or metastasis.\n10. Are pregnant or planning to become pregnant during the study or within 6 months following the last dose of AN9025. Plan to be breastfeeding from the initial dose of study treatment or within 6 months following the last dose of AN9025.\n11. Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator.\n12. Use of other herbal supplements, traditional medicines, or prescription medications that are known or suspected to interact with the investigational product or effect disease treatment\u002Fside effect management, as determined by the study Investigator.\n13. Known allergic reaction against any of the components of the study treatments.\n14. Current use of drugs known to be strong or moderate inhibitors or inducers of isoenzyme cytochrome P450 3A4 (CYP3A4) including herbal medications.\n15. Current use of drugs known to be of P-glycoprotein (P-gp) inhibitors.\n16. Participants who are unable to discontinue proton pump inhibitors (PPIs) for at least 5 days prior to the first dose of AN9025, or unable to abstain from PPI use throughout the study treatment period.\n17. Participant likely to not be available to complete all protocol-required study visits or procedures, and\u002For to comply with all required study procedures to the best of the participant and Investigator's knowledge.",{"count":91,"type":20},118,[23],"The goal of this clinical trial is to learn determine if AN9025 is safe and tolerable to treat solid cancer tumors with specific genetic mutations. It will help identify doses for use in future testing and establish the safety profile of the drug. The main questions it aims to answer are:\n\nWhich dose(s) of AN9025 are safe and tolerable for use in evaluating anti-tumor activity in participants with Rat Sarcoma oncogene (RAS) mutated solid tumors?\n\nWhat medical problems do participants have when taking AN9025?\n\nParticipants will:\n\nTake AN9025 by mouth every day or once a week until their disease progresses, they experience severe ill side effects from taking the drug, or withdraw from the study due to their own choice or as recommended by their physician.\n\nVisit the clinic 3-4 times during the first 21 days of treatment for study testing, blood draws and tumor tissue sample collection (if needed). The blood draws will be used to check drug levels in the participants blood for research purposes.\n\nVisit the clinic every 21 days for checkups and tests and monitoring of participant progress.\n\nReturn to the clinic at 14 and 30 days after AN9025 treatment is stopped. Participants will be contacted every 3 months to check on the participants disease status and general well being.\n\nParticipants may also partake in a food effect study, where the effect of eating is studied to see if there is any effect on AN9025 in the body.",[95,28],"Solid Tumors (Phase 1)",[97,98,99,100,101,102,103],"RAS","RAS (ON)","RAS Solid Tumor","KRAS G12X(C\u002FD\u002FV)","KRAS G13D","NRAS Q61X(L\u002FK)","Oral Pan RAS medication","2026-06-05",{"date":106,"type":37},"2026-06-08",{"date":108,"type":37},"2026-01-28",{"date":110,"type":20},"2028-06-01",{"name":112,"class":44},"Adlai Nortye Biopharma Co., Ltd.",{"id":114,"slug":115,"hasResults":11,"nctId":116,"briefTitle":117,"officialTitle":118,"acronym":4,"eligibilityCriteria":119,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":120,"targetDuration":4,"studyType":21,"phases":122,"briefSummary":123,"conditions":124,"keywords":130,"overallStatus":73,"whyStopped":4,"lastUpdateSubmitDate":138,"lastUpdatePostDateStruct":139,"startDateStruct":141,"completionDateStruct":143,"leadSponsor":145,"locationsCount":147},"100586992","phase-1-study-to-evaluate-the-safety-tolerability--efficacy-of-tng462-in-combination-in-pdac--nsclc-patients-100586992","NCT06922591","Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC Patients","A Phase 1\u002F2, Multicenter, Open-Label Study to Evaluate Safety, Tolerability & Antitumor Activity of TNG462 in Combination With Other Agents in Patients With Pancreatic Cancer With MTAP Loss and Pancreatic or Non-Small Cell Lung Cancer With MTAP Loss & RAS Mutation","Inclusion Criteria:\n\n1. Is ≥18 years of age at the time of signature of the main study ICF.\n2. Has an ECOG PS of 0 or 1.\n3. Has a tumor with loss of MTAP protein or bi-allelic deletion of the MTAP gene\n4. Arms A and B only: Has a tumor with a RAS mutation\n5. Pathologically documented metastatic PDAC or locally advanced, recurrent or metastatic NSCLC\n6. Has received prior standard therapy\n7. Arms A and B only: Must not have received prior RAS-targeted therapy\n8. Has evidence of measurable disease based on RECIST v1.1.\n9. Adequate organ function\n10. Must be able to swallow tablets.\n11. Negative pregnancy test at screening\n12. Written informed consent must be obtained according to local guidelines\n\nExclusion Criteria:\n\n1. Has received prior treatment with a PRMT5 inhibitor, or MAT2A inhibitor\n2. Arms A and B only: Prior enrollment in any phase 3 clinical trial of RMC-6236 or RMC-9805\n3. Known allergy, hypersensitivity or intolerance to TNG462 (all arms), RMC-6236 Arm A), RMC-9805 (Arm B), mFOLFIRINOX (Arm C), gemcitabine\u002Fnab-paclitaxel (Arm D) or their excipients\n4. Has uncontrolled intercurrent illness that will limit compliance with the study requirements.\n5. Has an active infection requiring systemic therapy.\n6. Is currently participating in or has planned concurrent participation in a study of another investigational agent or device.\n7. Has impairment of GI function or disease that may significantly alter the absorption of the oral medications\n8. Has known or suspected active or untreated CNS metastases associated with progressive neurological symptoms\n9. Has current active liver disease from any cause\n10. Is known to be HIV positive, unless all the following criteria are met:\n\n    1. CD4+ count ≥300\u002FµL.\n    2. Undetectable viral load.\n    3. Receiving highly active antiretroviral therapy\n11. Has clinically relevant cardiovascular disease\n12. History of or presence of active interstitial lung disease\n13. Is a female patient who is pregnant or lactating\n14. Is unwilling or unable to comply with the scheduled visits, study treatment administration plan, laboratory tests or other study procedures and study restrictions.\n15. Has a prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion may affect the safety of the patient or impair the ability to assess study results",{"count":121,"type":20},183,[23,24],"TNG462-C102 is a Phase 1\u002F2, open-label, multicenter study designed to determine the safety, tolerability, PK, PD, and preliminary antineoplastic activity of oral TNG462 in combination with RMC-6236, RMC-9805, mFOLFIRINOX or gemcitabine\u002Fnab-paclitaxel. The study comprises a dose escalation phase and a dose expansion phase.",[31,125,126,28,127,59,128,129],"PDAC - Pancreatic Ductal Adenocarcinoma","NSCLC","MTAP Deletion","Pancreatic Cancer Metastatic","Thoracic Cancer",[131,132,133,134,135,136,137],"PRMT5 inhibitor","RAS G12D","Multi RAS","RMC-9805","RMC-6236","Thoracic","Targeted therapy","2026-05-12",{"date":140,"type":37},"2026-05-14",{"date":142,"type":37},"2025-05-31",{"date":144,"type":20},"2027-12",{"name":146,"class":44},"Tango Therapeutics, Inc.",18,{"id":149,"slug":150,"hasResults":11,"nctId":151,"briefTitle":152,"officialTitle":153,"acronym":4,"eligibilityCriteria":154,"healthyVolunteers":155,"sex":16,"minAge":4,"maxAge":4,"enrollmentInfo":156,"targetDuration":158,"studyType":159,"phases":4,"briefSummary":160,"conditions":161,"keywords":4,"overallStatus":73,"whyStopped":4,"lastUpdateSubmitDate":175,"lastUpdatePostDateStruct":176,"startDateStruct":178,"completionDateStruct":180,"leadSponsor":182,"locationsCount":185},"100392859","rasopathy-biorepository-100392859","NCT04395495","RASopathy Biorepository","Investigation Into the Natural History and Metabolic and Molecular Basis of RASopathies.","Inclusion Criteria:\n\n* Patients with a suspected or known diagnosis of any of the group of disorders known as RASopathies (e.g., Neurofibromatosis, Costello Syndrome, Noonan Syndrome). Diagnosis may be made clinically and\u002For confirmed through genetic testing.\n* Unaffected relatives of patients with a suspected or known diagnosis of any of the group of disorders known as RASopathies.\n\nExclusion Criteria:\n\n* Individuals who do not have a suspected or definite diagnosis of a RASopathy.\n* Individuals who do not have a relative with a suspected or definite diagnosis of a RASopathy.\n* Patients who do not have the ability\u002Fcapacity to undergo the informed consent process OR whose parent\u002Flegal guardian is unable to undergo the informed consent process.",true,{"count":157,"type":20},1000,"50 Years","OBSERVATIONAL","The RASopathies are a group of developmental disorders caused by genetic changes in the genes that compose the Ras\u002Fmitogen activated protein kinase (MAPK) pathway. New RASopathies are being diagnosed frequently. This pathway is essential in the regulation of the cell cycle and the determination of cell function. Thus, appropriate function of this pathway is critical to normal development. Each syndrome in this group of disorders has unique phenotypic features, but there are many overlapping features including facial features, heart defects, cutaneous abnormalities, cognitive delays, and a predisposition to malignancies. This research study proposes to collect and store human bio-specimens from patients with suspected or diagnosed RASopathies. Once obtained, blood and\u002For tissue samples will be processed for: metabolic function studies, biomarkers, genetic studies, and\u002For the establishment of immortalized cell lines. In addition, data from the medical record (including neuropsychological evaluations) and surveys will be stored to create a longitudinal database for research conducted at CCHMC or at other research institutions.",[28,162,163,164,165,166,167,168,169,170,171,172,173,174],"Neurofibromatosis 1","Noonan Syndrome","Noonan Syndrome With Multiple Lentigines","Noonan Neurofibromatosis Syndrome","Cardiofaciocutaneous Syndrome","Costello Syndrome","Legius Syndrome","Smith-Kingsmore Syndrome","MTOR Gene Mutation","GATOR-1 Gene Mutation","SYNGAP1-Related Intellectual Disability","DLG4","MAPK1 Gene Mutation","2025-12-10",{"date":177,"type":37},"2025-12-18",{"date":179,"type":37},"2017-06-27",{"date":181,"type":20},"2065-12",{"name":183,"class":184},"Children's Hospital Medical Center, Cincinnati","OTHER",1,{"id":187,"slug":188,"hasResults":11,"nctId":189,"briefTitle":190,"officialTitle":191,"acronym":4,"eligibilityCriteria":192,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":193,"targetDuration":4,"studyType":21,"phases":195,"briefSummary":196,"conditions":197,"keywords":201,"overallStatus":73,"whyStopped":4,"lastUpdateSubmitDate":204,"lastUpdatePostDateStruct":205,"startDateStruct":207,"completionDateStruct":209,"leadSponsor":211,"locationsCount":213},"100539130","phase-1-pas-004-in-patients-with-advanced-solid-tumors-100539130","NCT06299839","PAS-004 in Patients With Advanced Solid Tumors","A Phase 1 Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PAS-004, a MEK (1\u002F2) Inhibitor, in Patients With MAPK Pathway-driven Advanced Solid Tumors With a Documented RAS, NF1, or RAF Mutation or Patients Who Have Failed BRAF\u002FMEK Inhibition","Inclusion Criteria:\n\n1. Capable of giving signed informed consent which includes compliance with the requirements, prohibitions and restrictions listed in the informed consent form (ICF).\n2. Patient has been informed both verbally and in writing about the objectives of the clinical study, the methods, the anticipated benefits, the potential risks, and the discomfort to which they may be exposed and has given written consent to participation in the study prior to study start and any study-related procedure.\n3. Patient must be at least 18 years of age at the time of signing the ICF.\n4. Patient must be able to swallow oral medication.\n5. Patient with histologically or cytologically diagnosed mitogen-activated protein kinase (MAPK) pathway driven advanced solid tumors with all of the following characteristics:\n\n   1. Tumor cannot be surgically resected\n   2. Patient has failed or is ineligible for standard of care therapy\n   3. Patient has no available treatment options with known clinical benefit\n   4. Documented evidence of rat sarcoma virus (RAS), neurofibromatosis type I (NF1), and\u002For rapidly accelerated fibrosarcoma (RAF) mutations. Patients with RAF mutations must have previously failed v-Raf murine sarcoma viral oncogene homolog B (BRAF) \u002F MEK inhibition.\n6. Prior to enrollment, patients without an existing prior genetic test result or adequate tumor tissue sample must agree to provide tumor tissue via biopsy (paraffin section or fresh tissue specimens) that will be sent for analysis to confirm eligibility.\n7. Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (Appendix B).\n8. Patient must have an estimated life expectancy of at least 12 weeks in the opinion of the Investigator at the time of informed consent.\n9. Patient must have adequate organ function at screening as indicated by the following laboratory value ranges:\n\n   1. Serum total bilirubin ≤ 1.5 × upper limit normal (ULN) (Serum total bilirubin can be ≤ 3.0 × ULN if patients have hemolysis or congenital hemolytic diseases)\n   2. Aspartate aminotransferase (AST) ≤ 2.5 × ULN or 5 × ULN for patient with liver metastases\n   3. Alanine aminotransferase (ALT) ≤ 2.5 × ULN or 5 × ULN for patient with liver metastases\n   4. Albumin ≥2 mg\u002FdL\n   5. Creatinine clearance ≥ 45 mL\u002Fmin (as calculated per Cockcroft-Gault)\n   6. Absolute neutrophil count (ANC) ≥ 1.5×109\u002FL\n   7. Platelets ≥ 100×109\u002FL\n   8. Hemoglobin ≥ 90 g\u002FL (Note: Criteria must be met without a transfusion within 2 weeks of obtaining the sample)\n10. Patient must agree to maintain abstinence (no heterosexual intercourse) or use a highly effective form of contraception during study treatment and for at least 90 days after the last dose of IP. Male patients must agree not to donate sperm while receiving IP and for at least 90 days after the last dose of IP.\n\nExclusion Criteria:\n\n1. Participation in another therapeutic clinical trial within 3 weeks of enrollment.\n2. Having received chemotherapy, radiotherapy, major surgery, targeted therapy, immunotherapy, or other antitumor treatment within 21 days of enrollment or five half-lives of the administered therapy, whichever occurs first.\n3. Known or active central nervous system metastases.\n\n   1. Patients with untreated brain metastases ≤ 30 mm that are asymptomatic, do not have significant edema, and do not require steroids or anti-seizure medications are eligible after discussion with the Medical Monitor.\n   2. Patients with previously treated brain metastases may participate provided they are stable after treatment and without evidence of progression by imaging for at least 4 weeks prior to the first dose of IP administration and are not using corticosteroids for at least 7 days prior to IP administration.\n   3. Patients with confirmed leptomeningeal disease are to be excluded.\n4. Unresolved toxicity from prior antitumor therapy defined as AEs \\> Grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, except for alopecia; neurotoxicity AEs of patients who have received prior chemotherapy needs to be restored to Grade 2 or below. Patients with ≥ Grade 3 bleeding within 4 weeks of first study treatment dose should be excluded.\n5. Taken a medication that is a strong cytochrome P450 (CYP3A) inhibitor or inducer within 14 days of initiation of study therapy dosing.\n6. Taken a known corrected QT (QTc) interval prolongating medication within 7 days of initiation or longer if the half-life of the QTc prolonging medication is such that the drug is not cleared from the body within 7 days (5 half-lives) of initiation of study therapy dosing.\n7. Active dysphagia, digestive system disease, malabsorption syndrome, or other conditions affecting PAS-004 absorption.\n8. Previous or current retinal vein stenosis, retinal detachment, central retinal vein occlusion, or currently active glaucoma.\n9. Active interstitial pneumonia, including clinically significant radiation pneumonitis.\n10. Impaired cardiac function or cardiac disease as indicated by:\n\n    1. Average QTc interval \\> 470 ms as calculated according to the QTc formula of the instrument at the research center where electrocardiogram (ECG) measurements are performed.\n    2. Grade ≥ 3 congestive heart failure per New York Heart Association (NYHA) guidelines.\n    3. Clinically significant arrhythmias, including but not limited to, complete left bundle branch conduction abnormalities and 2nd degree atrioventricular block.\n11. Pregnant or lactating female patients.\n12. Known allergy or hypersensitivity to the investigational product (IP), including excipients, or history of severe adverse reaction to any drug, or sensitivity to components of the IP.\n13. Clinically active bacterial, fungal, or viral infections, hepatitis B (hepatitis B virus surface antigen positive and hepatitis B virus DNA over 1000 IU\u002Fml) or hepatitis C (hepatitis C virus RNA positive), human immunodeficiency virus infection (HIV positive).",{"count":194,"type":20},48,[23],"The main purpose of this clinical trial is to test PAS-004 in people with advanced solid tumors with rat sarcoma virus (RAS), neurofibromatosis type I (NF1), or rapidly accelerated fibrosarcoma (RAF) mutations. The main questions it aims to answer are:\n\n* How well participants are able tolerate different doses of PAS-004, and\n* What side effects PAS-004 might have.\n\nStudy participants will have regular visits to the study doctor and be asked to have tests and exams done to check on their health and safety. Everyone participating in the study will take PAS-004 by mouth as a single dose, followed by one week observation, then once a day during the study, in 28-day cycles. Participants will continue on daily PAS-004 for up to 2 years, or until:\n\n* They decide to withdraw from the study, or\n* They experience unacceptable side effects, or\n* Their disease progresses, or another illness interferes with taking the study drug, or\n* The sponsors stops the study.",[28,198,199,200],"NF1 Mutation","RAF Mutation","Advanced Solid Tumors",[65,202,200,203],"malignant neoplasms","MAP Kinase Signaling Pathway","2025-11-25",{"date":206,"type":37},"2025-12-03",{"date":208,"type":37},"2024-02-29",{"date":210,"type":20},"2027-02",{"name":212,"class":44},"Pasithea Therapeutics Corp.",7,{"id":215,"slug":216,"hasResults":11,"nctId":217,"briefTitle":218,"officialTitle":219,"acronym":220,"eligibilityCriteria":221,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":222,"targetDuration":4,"studyType":21,"phases":224,"briefSummary":226,"conditions":227,"keywords":230,"overallStatus":73,"whyStopped":4,"lastUpdateSubmitDate":233,"lastUpdatePostDateStruct":234,"startDateStruct":236,"completionDateStruct":238,"leadSponsor":240,"locationsCount":243},"100422117","phase-3-study-in-mcrc-patients-rasbraf-wt-tissue-and-ras-mutated-liquid-biopsy-to-compare-folfiri-plus-cetuximab-or-bevacizumab-100422117","NCT04776655","Study in mCRC Patients RAS\u002FBRAF wt Tissue and RAS Mutated LIquid BIopsy to Compare FOLFIRI Plus CetuxiMAb or BevacizumaB","Phase III Study in mCRC Patients With RAS\u002FBRAF Wild Type Tissue and RAS Mutated in LIquid BIopsy to Compare in First-line Therapy FOLFIRI Plus CetuxiMAb or BevacizumaB (LIBImAb Study)","LIBImAb","Inclusion Criteria:\n\n1. Provision of written informed consent;\n2. Male or female \\> 18 years of age;\n3. Histologically confirmed diagnosis of colorectal adenocarcinoma RAS\u002FBRAF wild type (analysed either on primary and\u002For related metastasis);\n4. Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease;\n5. Patient with left colorectal cancer;\n6. Patients suitable for first line chemotherapy;\n7. Life expectancy \\> 3 months;\n8. At least one site of measurable disease per RECIST criteria ver. 1.1;\n9. ECOG Performance status = 2;\n10. Adequate bone marrow, liver and renal function assessed before starting study treatment;\n11. If DPD status is known it must be wild type. No restrictions are applied if DPD status in unknown;\n12. Women of childbearing potential must have a negative blood pregnancy test within 24 hr prior to the start of study treatment. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive.\n13. Subjects and their partners must be willing to avoid pregnancy during the trial and until 5 months for WOCBP (Women of Childbearing Potential) and 7 months for male subjects with female partners of WOCBP after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator (barriers contraceptive measure or oral contraception).\n\nExclusion Criteria:\n\n1. Previous chemotherapy treatment, with the exception of patient treated in adjuvant setting completed at least 6 months before the randomization;\n2. Any contraindication to the use of Cetuximab, Bevacizumab, Irinotecan, 5FU or folinic acid;\n3. Radiotherapy to any site within 4 weeks before the randomization;\n4. Serious, non-healing wound, ulcer, or bone fracture;\n5. Evidence of bleeding diathesis or coagulopathy;\n6. Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy;\n7. Additional malignancy in the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy;\n8. Active and untreated brain (CNS) metastases and\u002For carcinomatous meningitis;\n9. Active infection requiring systemic therapy or active disseminated intravascular coagulation;\n10. History of Human Immunodeficiency Virus (HIV) (HIV 1\u002F2 antobodies);\n11. Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection;\n12. Chronic, daily treatment with high-dose aspirin (\\>325 mg\u002Fday);\n13. Any previous venous thromboembolism \\> NCI CTCAE Grade 3;\n14. History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment. History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhoea;\n15. Current, recent (within 10 days prior to study treatment start) or ongoing treatment with anticoagulants for therapeutic purposes;\n16. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study;\n17. History of any severe hypersensitivity reactions to any monoclonal antibody;\n18. A significant concomitant disease which, in the investigating physician's opinion, rules out the patient's participation in the study",{"count":223,"type":20},280,[225],"PHASE3","This study is a prospective, randomized phase III, to evaluate if in patients with mCRC RAS\u002FBRAF wild type on tumor tissue and RAS mutations on liquid biopsy, treating in first line with antibody anti-VEGF (bevacizumab) plus chemotherapy (FOLFIRI) is superior in terms of PFS compared to standard treatment with antibody anti-EGFR (cetuximab) plus FOLFIRI, and then in patients RAS\u002FBRAF wild type on tumor tissue who develop RAS mutations on liquid biopsy after the beginning of the first line treatment with cetuximab plus FOLFIRI, in the absence of a clinical or radiological progression disease, to anticipate a change of treatment with bevacizumab plus FOLFIRI further impacts on the PFS.",[228,229,28],"Colorectal Cancer","Metastatic Colorectal Cancer",[231,232,97],"mCRC","liquid biopsy","2025-09-30",{"date":235,"type":37},"2025-10-02",{"date":237,"type":37},"2021-04-30",{"date":239,"type":20},"2026-05-04",{"name":241,"class":242},"Azienda USL Reggio Emilia - IRCCS","OTHER_GOV",4,{"id":245,"slug":246,"hasResults":11,"nctId":247,"briefTitle":248,"officialTitle":248,"acronym":249,"eligibilityCriteria":250,"healthyVolunteers":11,"sex":16,"minAge":4,"maxAge":251,"enrollmentInfo":252,"targetDuration":4,"studyType":159,"phases":4,"briefSummary":254,"conditions":255,"keywords":256,"overallStatus":73,"whyStopped":4,"lastUpdateSubmitDate":258,"lastUpdatePostDateStruct":259,"startDateStruct":261,"completionDateStruct":263,"leadSponsor":265,"locationsCount":267},"100384489","hematological-anomalies-in-children-with-rasopathy-100384489","NCT04286360","Hematological Anomalies in Children With Rasopathy","RAS-HEMATO","Inclusion Criteria:\n\n* Age \\\u003C 16 years\n* Patient newly diagnosed with genetically confirmed rasopathy : Noonan syndrome, type 1 neurofibromatosis, Noonan syndrome with multiple lentigines, CBL syndrome, Costello syndrome, cardiofaciocutaneous syndrome or Legius syndrome i.e. with a germline mutation of one of these genes: PTPN11, SOS1, NRAS, RAF1, BRAF, SHOC2, MEK1, MEK2, CBL, NF1, SPRED1, KRAS, HRAS, NF1, SHOC2, LZTR1, SOS2, RIT1, RASA2, RRAS, PPP1CB, or a new gene of interest published during the recruitment period\n* No history of hematological malignancy\n* Written informed consent obtained from the parents\n* Health insurance\n\nExclusion Criteria:\n\n* History of malignant hematological pathology","15 Years",{"count":253,"type":20},300,"During childhood, patients with RASopathies (Noonan syndrome and related diseases) can harbor various hematological anomalies ranging from isolated monocytosis, myelemia, thrombocytopenia or splenomegaly to myeloproliferative disorders. These anomalies may spontaneously disappear or persist, sometimes leading to juvenile myelomonocytic leukemia. Guidelines for initial screening and subsequent hematological follow-up have recently been published in France: peripheral blood analysis should be performed in all newly diagnosed patients and followed by biannual peripheral blood analysis in infants until the age of 2 years.\n\nIn order to describe the characteristics of these abnormalities in terms of their incidence, age of occurrence, evolution and relation to genotype, we are conducting a longitudinal prospective study whose aim is to analyze peripheral blood cell counts and smears at diagnosis and one year later. In patients \\\u003C3 years of age recruited at certain centers, biobanking of mononuclear cells will be performed. These data could yield a new insight into hematological anomalies in patients with RASopathies and thereby help physicians to determine the appropriate rhythm for hematological follow-up according to genotype.",[28],[257],"RASopathie","2024-06-03",{"date":260,"type":37},"2024-06-04",{"date":262,"type":37},"2020-11-11",{"date":264,"type":20},"2029-11",{"name":266,"class":184},"Assistance Publique - Hôpitaux de Paris",14,{"id":269,"slug":270,"hasResults":11,"nctId":271,"briefTitle":272,"officialTitle":273,"acronym":4,"eligibilityCriteria":274,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":275,"targetDuration":4,"studyType":21,"phases":277,"briefSummary":278,"conditions":279,"keywords":4,"overallStatus":73,"whyStopped":4,"lastUpdateSubmitDate":281,"lastUpdatePostDateStruct":282,"startDateStruct":284,"completionDateStruct":286,"leadSponsor":288,"locationsCount":185},"100540764","phase-2-ice-study-combination-of-irinotecan-plus-cetuximab-and-envafolimab-as-a-rechallenge-regimen-in-mcrc-100540764","NCT06321081","ICE Study: Combination of Irinotecan Plus Cetuximab and Envafolimab as a Rechallenge Regimen in mCRC","ICE Study: a Clinical Study of the Combination of Irinotecan Plus Cetuximab and Envafolimab as a Rechallenge Regimen in mCRC","Inclusion Criteria:\n\n* Signed written informed consent before any trial-related procedure is undertaken that is not part of the standard patient management.\n\nMale or female subjects aged ≥ 18 years. Histologically proven diagnosis of colorectal adenocarcinoma. Diagnosis of metastatic disease. RAS (NRAS and KRAS exon 2,3 and 4) and BRAF wild-type in liquid biopsy at screening (according to NGS) Efficacy of any front-line therapies containing cetuximab or irinotecan with a major response achieved (i.e. complete or partial response according to RECIST criteria v1.1)..\n\nMore than 2 months since the last dose of cetuximab administered in first line treatment before randomization.\n\nMeasurable disease according to RECIST criteria v1.1. ECOG PS of 0 to 1 at trial entry. Estimated life expectancy of more than 12 weeks. Adequate hematological function defined by white blood cell (WBC) count ≥ 2.5 × 109\u002FL with absolute neutrophil count (ANC) ≥ 1.5 × 109\u002FL, lymphocyte count ≥ 0.5 × 109\u002FL, platelet count ≥ 100 × 109\u002FL, and hemoglobin ≥ 9 g\u002FdL (may have been transfused).\n\nAdequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN for all subjects or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).\n\nAdequate renal function defined by an estimated creatinine clearance \\> 30 mL\u002Fmin according to the Cockcroft-Gault formula (or local institutional standard method).\n\nEffective contraception for both male and female subjects throughout the study and for at least 2 months after last study treatment administration if the risk of conception exists (Note: The effects of the trial drug on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use effective contraception, defined as 2 barrier methods, or 1 barrier method with a spermicide, an intrauterine device, or use of oral female contraceptive. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, the treating physician should be informed immediately).\n\nExclusion Criteria:\n\n* Any contraindication to cetuximab and\u002For envafolimab. Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix.\n\nPregnancy. Breastfeeding. Participation in a clinical study or experimental drug treatment within 30 days before enrollment.\n\nSubjects receiving immunosuppressive agents (such as steroids) for any reason, should be tapered off these drugs before initiation of the trial treatment, with the exception of:\n\nSubjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to ≤ 10 mg prednisone daily Intranasal, inhaled, topical steroids, Local steroid injection (e.g., intra-articular injection) Systemic corticosteroids at physiologic doses ≤ 10 mg\u002Fday of prednisone or equivalent Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) No ongoing neurological symptoms related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) Prior organ transplantation, including allogeneic stemcell transplantation\n\nSignificant acute or chronic infections including, among others:\n\nKnown history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome\n\nActive autoimmune disease that might deteriorate when receiving an immunostimulatory agent:\n\nSubjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.\n\nSubjects requiring hormone replacement with corticosteroids are eligible if steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or equivalent prednisone per day.\n\nAdministration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable.\n\nActive infection requiring systemic therapy. Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be ≤ 10 mg per day of equivalent prednisone.\n\nKnown severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v 5 Grade ≥ 3), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma).\n\nHistory of hypersensitivity to Polysorbate 80 that led to unacceptable toxicity requiring treatment cessation.\n\nPersisting toxicity related to prior therapy of Grade \\> 1 NCI- CTCAE v 5.0. Known alcohol or drug abuse. Clinically significant (that is active) cardiovascular disease: cerebral vascular accident\u002Fstroke (\\\u003C6 months prior to enrollment), myocardial infarction (\\\u003C6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), or serious uncontrolled cardiac arrhythmia requiring medication.\n\nHistory of keratitis, ulcerative keratitis or severe dry eye. Since contact lent use is also a risk factor for keratitis and ulceration, it is not recommended.\n\nOther severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.\n\nLegal incapacity or limited legal capacity.",{"count":276,"type":20},60,[24],"This is a non-profit phase II, open, clinical study of the combination of irinotecan plus cetuximab and envafolimab as a rechallenge regimen, in pre-treated RAS\u002FBRAF wild type metastatic colorectal cancer patients (according to liquid biopsy at baseline). Patients have been treated in front lines with irinotecan and cetuximab and had a clinical benefit (complete or partial response) from both of them, no matter whether they had treated by any PD-1 inhibitor before.",[28,229,280],"MSS","2024-03-14",{"date":283,"type":37},"2024-03-20",{"date":285,"type":37},"2024-03-01",{"date":287,"type":20},"2026-08-14",{"name":289,"class":242},"Beijing Hospital",{"id":291,"slug":292,"hasResults":11,"nctId":293,"briefTitle":294,"officialTitle":295,"acronym":4,"eligibilityCriteria":296,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":297,"enrollmentInfo":298,"targetDuration":4,"studyType":21,"phases":300,"briefSummary":301,"conditions":302,"keywords":4,"overallStatus":73,"whyStopped":4,"lastUpdateSubmitDate":305,"lastUpdatePostDateStruct":306,"startDateStruct":308,"completionDateStruct":310,"leadSponsor":312,"locationsCount":185},"100532899","phase-2-cadonilimab-in-combination-with-bevacizumab-and-folfox-regimen-for-the-first-line-treatment-of-advanced-unresectable-mss-type-ras-mutated-metastatic-colorectal-cancer-100532899","NCT06218810","Cadonilimab in Combination With Bevacizumab and FOLFOX Regimen for the First-Line Treatment of Advanced Unresectable MSS-Type, RAS-Mutated Metastatic Colorectal Cancer","Cadonilimab in Combination With Bevacizumab and FOLFOX Regimen for the First-Line Treatment of Advanced Unresectable MSS-Type, RAS-Mutated Metastatic Colorectal Cancer: A Single-Arm, Open-Label, Multicenter Phase II Study","Inclusion Criteria:\n\n1. Voluntarily sign a written ICF.\n2. Age at enrollment: ≥ 18 years old, ≤ 75 years old, both male and female.\n3. The Eastern Cancer Collaborative Organization (ECOG) has a physical fitness score of 0 or 1.\n4. The expected survival period is ≥ 3 months.\n5. Subjects diagnosed with metastatic colorectal adenocarcinoma by histology or cytology.\n6. Colorectal cancer patients who have not received systematic anti-tumor therapy in the past and are not suitable for radical surgical resection or local treatment.\n7. Genetic testing results indicate pMMR or MSS; RAS mutation;\n8. According to RECIST v1.1, there is at least one measurable lesion that is suitable for repeated and accurate measurements. Note: Brain metastases cannot be used as target lesions; For lesions that have received radiation therapy before, it is not recommended to select them as target lesions. If there are no other lesions that meet the target lesion criteria, and the lesion can be measured according to RECIST v1.1 and there is objective evidence to prove significant progression after radiation therapy, the irradiated lesion can be considered as a target lesion.\n\nExclusion Criteria:\n\n1. Patients with known MSI-H or dMMR.\n2. Participants of RAS wild-type.\n3. Subjects suffered from other malignant tumors within 3 years before enrollment, except for cured local tumors (such as basal cell skin cancer, squamous cell skin cancer, superficial bladder cancer, cervical carcinoma in situ, etc.).\n4. Simultaneously enroll in another clinical study, unless it is an observational, non-interference clinical study or a follow-up period of an intervention study.\n5. Received systematic anti-tumor therapy (chemotherapy) within 3 weeks prior to the first administration; Palliative local treatment was performed on non target lesions within 2 weeks prior to the first administration; Received non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, etc., excluding IL-11 used to treat thrombocytopenia) within 2 weeks before the first administration; Chinese herbal medicine or traditional Chinese patent medicines and simple preparations with anti-tumor indications was received within 1 week before the first administration.\n6. Have received any immunotherapy against tumors in the past, including immune checkpoint inhibitors (such as anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-CTLA-4 antibodies, etc.), immune checkpoint agonists (such as ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), immune cell therapy, and any treatment targeting the immune mechanism of tumors.\n7. Patients with active autoimmune diseases that require systematic treatment within the past two years (such as using medication to improve the condition, corticosteroids, immunosuppressive agents), and replacement therapy (such as thyroid hormone, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary dysfunction) are not considered as systematic treatment.\n8. A history of active or previous inflammatory bowel disease (such as Crohn's disease, ulcerative colitis, or chronic diarrhea).\n9. History of immunodeficiency; HIV antibody test positive individuals; Currently using systemic corticosteroids or other immunosuppressants for a long time.\n10. Subjects who are known to have active pulmonary tuberculosis (TB) and suspected to have active TB need to undergo clinical examination to exclude them; Known active syphilis infection.\n11. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.\n12. Previous or current non infectious pneumonia\u002Finterstitial lung disease requiring systemic glucocorticoid treatment.","75 Years",{"count":299,"type":20},53,[24],"The dual immunotherapy regimen significantly outperformed previous chemotherapy or immunomonotherapy for MSS type advanced CRC in two key efficacy indicators, ORR and PFS. Researchers have also conducted in-depth analysis of patient transcriptomics, immune microenvironment characteristics, and other related information, which is expected to guide more accurate immune combination therapy for CRC in the future. Our team plans to conduct a multicenter, prospective, single arm clinical trial in patients with RAS mutant MSS unresectable metastatic colorectal cancer, with a focus on observing the 1-year progression free survival rate of the combination of two chemotherapy drugs, bevacizumab and Cadonilimab, as well as ORR, perioperative safety, and long-term survival.",[229,303,28,304],"Microsatellite Stable Colorectal Carcinoma","Cadonilimab","2024-01-20",{"date":307,"type":37},"2024-01-23",{"date":309,"type":37},"2024-01-01",{"date":311,"type":20},"2026-12-31",{"name":313,"class":184},"Fudan University",{"id":315,"slug":316,"hasResults":11,"nctId":317,"briefTitle":318,"officialTitle":319,"acronym":320,"eligibilityCriteria":321,"healthyVolunteers":155,"sex":16,"minAge":17,"maxAge":322,"enrollmentInfo":323,"targetDuration":4,"studyType":21,"phases":325,"briefSummary":326,"conditions":327,"keywords":333,"overallStatus":73,"whyStopped":4,"lastUpdateSubmitDate":334,"lastUpdatePostDateStruct":335,"startDateStruct":337,"completionDateStruct":339,"leadSponsor":341,"locationsCount":185},"100533709","phase-2-leflunomide-or-combination-of-mek-inhibitor-and-hydroxychloroquine-for-refractory-patients-with-ras-mutations-100533709","NCT06229340","Leflunomide or Combination of MEK Inhibitor and Hydroxychloroquine for Refractory Patients With RAS Mutations","New Therapeutic Approaches for Tumors With RAS Gene Mutations","NТО-RAS","Inclusion Criteria:\n\n1. Patient is able to provide informed consent and sign approved consent forms to participate in the study.\n2. Patient age is at least 18 years old.\n3. Performance status Eastern Cooperative Oncology Group (ECOG) 0-2.\n4. Histologically confirmed metastatic metastatic disease stage 4.\n5. Must have documented RAS (KRAS, HRAS, NRAS) mutation identified within the last 5 years by a local test on tumor tissue.\n6. More than 2 lines of standard drug antitumor therapy in the anamnesis.\n7. Must have disease progression as defined by RECIST version 1.1 criteria\n8. Appropriate hematologic and liver function:\n\n   * Absolute neutrophil count (ANC) ≥ 1.5 x 109\u002FL (1500\u002FμL)\n   * Lymphocyte count ≥ 0.5 x 109\u002FL (500\u002FμL)\n   * Platelet count ≥ 100 x 109\u002FL (100,000\u002FμL) without transfusion\n   * Hemoglobin ≥ 90 g\u002FL without transfusion.\n   * Creatinine clearance ≥ 40 mL\u002Fmin\n   * Serum albumin ≥ 25 g\u002FL (2.5 g\u002FdL)\n   * Serum bilirubin ≤ 1.5 x HGH, with the following exception:\n   * Patients with known Gilbert's disease or liver metastases: serum bilirubin level ≤ 3 x IUH\n   * AST, ALT, and alkaline phosphate ≤ 2.5 x HGN;\n\n10\\. For women of childbearing potential: consent to abstinence (abstain from heterosexual intercourse) or use at least two forms of effective contraception with an ineffectiveness rate \\\u003C 1% per year during treatment.\n\n11\\. Patients with asymptomatic new or advanced brain metastases (active brain metastases) are eligible to participate if the treating physician determines that localized treatment is not required.\n\nExclusion Criteria:\n\n1. Age over 85 years.\n2. Рresence of acute or active chronic infections.\n3. Impaired renal and hepatic function; - left ventricular ejection fraction (LVEF) \\\u003C 45%\n4. Known history of acute or chronic hepatitis B or C due to known potential hepatotoxicity of leflunomide.\n5. History of allergic reactions associated with compounds similar in chemical or biological composition to leflunomide or teriflunomide or other drugs in the combination.\n6. Uncontrolled intercurrent disease, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmias, or mental illness\u002Fsocial situations that limit study compliance.\n7. Patients should not be pregnant or breastfeeding due to the potential for teratogenic effects and side effects of planned chemotherapeutic regimens.\n8. History of retinal disease (retinal tear, exudate, hemorrhage) or retinal vein occlusion, central serous retinopathy or retinal pigment epithelium detachment, or current risk factors for ROS (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).\n\nExit criteria:\n\n1. Refusal to continue participation in the study.\n2. Intolerable toxicity.\n3. Progression according to RECIST 1.1 and IRECIST criteria or clinically significant (in the opinion of the physician) progression requiring a change in anticancer treatment.\n4. Non-compliance with IND procedures.","85 Years",{"count":324,"type":20},20,[24],"There is a huge variety of nucleotide substitutions that activate RAS. The search for new \"universal\" drugs for the RAS pathway that either interfere with RAS upregulation upstream in the signaling pathway or offset the consequences of RAS activation is important for improving therapeutic outcomes for patients with refractory malignancies.\n\nThe use of leflunomide or the combination of MEK inhibitor + hydroxychloroquine ± bevacizumab is promising for patients with mutations in RAS cascade genes who have failed all existing treatment standards.",[28,328,329,330,59,331,332],"Ras (Kras or Nras) Gene Mutation","Colorectal Cancer Recurrent","Pancreas Cancer","Melanoma","Refractory Cancer",[28,328,228,330,331,59,332],"2024-01-19",{"date":336,"type":37},"2024-01-29",{"date":338,"type":37},"2023-10-03",{"date":340,"type":20},"2026-10-01",{"name":342,"class":184},"N.N. Petrov National Medical Research Center of Oncology"]