[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Gruppo Oncologico del Nord-Ovest\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":305},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,10,0,[8,43,69,104,135,165,194,228,256,283],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":28,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":31,"lastUpdatePostDateStruct":32,"startDateStruct":35,"completionDateStruct":37,"leadSponsor":39,"locationsCount":42},"100630255","phase-2-effect-of-postbiotics-on-microbiota-and-systemic-immunomodulation-of-pembrolizumab-as-first-line-therapy-in-recurrentmetastatic-head-and-neck-squamous-cell-carcinoma-rm-hnscc-100630255",false,"NCT07485296","Effect of Postbiotics on Microbiota and Systemic Immunomodulation of Pembrolizumab as First-Line Therapy in Recurrent\u002FMetastatic Head and Neck Squamous Cell Carcinoma (RM HNSCC)","A Phase II, Randomized, Double-blind, Placebo Controlled, Multicenter Pilot Study to Evaluate the Effect of Postbiotics on Microbiota and Systemic Immunomodulation of Pembrolizumab as First Line Standard of Care in Patients With Recurrent\u002FMetastatic Head and Neck Squamous Cell Carcinoma (RM HNSCC)","POST-BIO","-Inclusion Criteria\n\n1. Be willing and able to provide informed consent for the trial and its procedure;\n2. Histological confirmation of HNSCC;\n3. Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) HNSCC;\n4. For oropharyngeal cancers, known IHC p16+ and\u002For ISH HPV status;\n5. Positive PD-L1 Combined Proportionate Score (CPS);\n6. Presence of neoplastic lesion deemed safely accessible for tumor biopsy by the investigator;\n7. No prior systemic therapy for RM HNSCC;\n8. Eligible to receive pembrolizumab as the standard of care\n9. ECOG Performance Status ≤ 2;\n10. Measurable disease as per RECIST 1.1;\n11. Males and females, ages ≥18;\n12. Adequate renal function defined as calculated creatinine clearance ≥30 milliliters per minute (mL\u002Fmin) per the Cockcroft and Gault formula or Serum creatinine \\\u003C 1.5 x upper limit of normal (ULN);\n13. Adequate liver function defined by AST or ALT \\\u003C 3 x ULN (\\\u003C 5 x ULN if liver metastases are present), and total bilirubin \\\u003C 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin up to 3.0 mg\u002FdL);\n14. Adequate bone marrow function defined by any of the following laboratory test findings: - WBC \\> 2,000\u002Fmm3, Neutrophils \\> 1,500\u002Fmm3, Platelets \\> 100,000\u002Fmm3;\n15. Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;\n16. Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 6.3 and 6.4 - Contraception, for the course of the study through 120 days after the last dose of study medication; Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.\n17. Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section 6.3 and 6.4 - Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject; 18.\n\nWillingness to provide blood, buccal swab samples, stool samples and tissue (if deemed safe by the investigator) for translational research.\n\n\\- Exclusion Criteria\n\n1. Presence of untreated brain metastases. Patients with treated brain metastases must be stable for 4 weeks after completion of treatment and have documented stability on pre-study imaging. Patients must have no clinical symptoms from brain metastases and have no requirement for systemic corticosteroids amounting to \\>10 mg\u002Fday of prednisone or its equivalent for at least 2 weeks prior to first dose of study drug. Patients with known leptomeningeal metastases are excluded, even if treated.\n2. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.\n3. Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll.\n4. Active interstitial lung disease (ILD)\u002Fpneumonitis or history of ILD\u002Fpneumonitis requiring treatment with systemic steroids\n5. Current use, or intent to use, probiotics, yogurt or bacterial fortified foods during the period of treatment.\n6. Any condition requiring systemic treatment with corticosteroids (\\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.\n7. Uncontrolled adrenal insufficiency.\n8. Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.\n9. Not recovered to ≤ Grade 1 toxicities related to any prior therapy before administration of study drug.\n10. Women who are pregnant or breastfeeding.\n11. History of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry\n12. Any of the following laboratory test findings:\n\n    * WBC \\\u003C 2,000\u002Fmm3\n    * Neutrophils \\\u003C 1,500\u002Fmm3\n    * Platelets \\\u003C 100,000\u002Fmm3\n    * AST or ALT \\> 3 x ULN (\\> 5 x ULN if liver metastases are present)\n    * Total bilirubin \\> 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin 3.0 mg\u002FdL)\n    * Calculated creatinine clearance \\\u003C30 millimeters per minute (mL\u002Fmin) per the Cockcroft and Gault formula or serum creatinine \\>1.5 x upper limit of normal (ULN)\n13. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1\u002F2 antibodies).\n14. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \\[qualitative\\] is detected).\n15. Has a known history of active TB (Bacillus Tuberculosis)\n16. Has previously received an organ transplant\n17. Has previously received bone marrow transplantation\n18. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.","ALL","18 Years",{"count":20,"type":21},45,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","phase II, randomized, double-blind, placebo controlled, non pharmacological clinical trial that aims to determine the effect of postbiotics Postbiotix-HLA™ on immuno-related adverse events (irAEs) in patients with recurrent\u002Fmetastatic head and neck squamous cell carcinoma (RM HNSCC) treated with in first line pembrolizumab as standard of care (SoC).\n\nThe selected patient population will be randomised to receive the postbiotics Postbiotix-HLA™ or placebo for 4 cycles while in treatment with pembrolizumab as per clinical practice.",[27],"Head & Neck Squamous Cell Carcinoma",[29],"recurrent\u002Fmetastatic head and neck squamous cell carcinoma (RM HNSCC)","RECRUITING","2026-03-17",{"date":33,"type":34},"2026-03-20","ACTUAL",{"date":36,"type":34},"2026-01-27",{"date":38,"type":21},"2032-12",{"name":40,"class":41},"Gruppo Oncologico del Nord-Ovest","OTHER",1,{"id":44,"slug":45,"hasResults":11,"nctId":46,"briefTitle":47,"officialTitle":48,"acronym":4,"eligibilityCriteria":49,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":50,"targetDuration":4,"studyType":22,"phases":52,"briefSummary":53,"conditions":54,"keywords":57,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":61,"lastUpdatePostDateStruct":62,"startDateStruct":64,"completionDateStruct":66,"leadSponsor":68,"locationsCount":42},"100504220","phase-2-pre-operative-targeted-treatments-in-molecularly-selected-resectable-colorectal-cancer-unicorn-100504220","NCT05845450","Pre-operative Targeted Treatments in Molecularly Selected Resectable Colorectal Cancer (UNICORN)","Window-of-opportunity Umbrella Platform Trial of Short-course Pre-operative Targeted Treatments in Patients With Molecularly Selected and Resectable Primary Colorectal Cancer: the UNICORN Study","Inclusion Criteria:\n\nGeneral inclusion criteria\n\n* Provide a signed and dated informed consent document.\n* Age ≥ 18 years at time of informed consent.\n* ECOG PS of 0 and 1.\n* Histologically confirmed colorectal cancer adenocarcinoma that is judged as initially resectable with elective surgery aimed at radical intent with R0 margins as per multidisciplinary team assessment.\n* Radiological stage cT3-4, N0-2, M0 using computed tomography (CT) as in the pivotal FOxTROT study.\n* Patients with rectal cancer candidate for R0 resection, not requiring pre-operative radiotherapy based on multidisciplinary team assessment, with the following characteristics on high-resolution thin slice (3 mm) contrast-enhanced magnetic resonance imaging (MRI):\n\n  * ≤ T3a defined at the MRI (perivisceral fat infiltration \\\u003C2 mm) and clinical N0\n  * Upper-medium, defined as tumors with distal margin ≥ 5 cm from the anal verge.\n  * Absence of mesorectal fascia invasion, as defined as a distance ≥ 1 mm between tumor and the mesorectal fascia.\n* Able to provide enough archival FFPE tumor specimen that is already available from initial diagnostic procedures for the purpose of molecular pre-screening.\n* Presence of one of the selected molecular profile\u002Falteration after central pre-screening and necessary for the assignment to a matching treatment cohort.\n* No prior systemic treatment for colorectal cancer or neoadjuvant radiation therapy for rectal cancer.\n* Adequate bone marrow function (absolute neutrophil count ≥ 1.5 × 109\u002FL; platelet count ≥ 100 × 109\u002FL; hemoglobin ≥ 9.0 g\u002FdL)\n* Adequate renal function characterized by serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated by Cockroft-Gault formula or directly measured creatinine clearance ≥ 50 mL\u002Fmin at screening.\n* Adequate hepatic function (serum total bilirubin ≤ 1.5 × ULN and \\\u003C 2 mg\u002FdL. Note: Patients who have a total bilirubin level 1.5 × ULN will be allowed if their indirect bilirubin level is ≤ 1.5 × ULN; Alanine aminotransferase and\u002For aspartate aminotransferase ≤ 2.5 × ULN).\n* Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. 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. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.\n* Subjects and their partners must be willing to avoid pregnancy during the trial and until a specific time interval after the last trial treatment: 7 months for female and 4 for male patients after last dose of trastuzumab-deruxtecan, 3 months for durvalumab, botensilimab and balstilimab and 2 months for panitumumab. 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 (barrier contraceptive measure or oral contraception).\n* Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.\n\nSpecific inclusion criteria for each Cohort\n\nCOHORT 1: pMMR\u002FMSS status and HER2-positive status and LVEF ≥ 50% within 28 days before enrolment, international normalised ratio or Prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤ 1.5 × ULN\n\nCOHORT 2: Proofread domain mutations in POLE or POLD1 associated with ultra-mutated status, i.e. tumor mutational burden \\>100 Mut\u002FMb.\n\nCOHORT 3: pMMR\u002FMSS status and wild-type status for RAS and BRAF, absence of molecular predictors of resistance (PRESSING panel negative), Left-sided and rectal primary tumor location, according to the specific inclusion criterion regarding rectal tumors.\n\nCOHORT 4: pMMR\u002FMSS status and absence of HER2 overexpression\u002Famplification, absence of POLE\u002FD1 proof-read domain pathogenic mutation associated with ultra-mutated status and absence of KRAS G12C mutation.\n\nCOHORT 5: pMMR\u002FMSS status and absence of of HER2 overexpression\u002Famplification, absence of POLE\u002FD1 proof-read domain pathogenic mutation associated with ultra-mutated status.\n\nCOHORT 6: dMMR\u002FMSI-H status and absence of POLE\u002FD1 proof-read domain pathogenic mutation associated with ultra-mutated status.\n\nCOHORT 7: dMMR\u002FMSI-H status and absence of POLE\u002FD1 proof-read domain pathogenic mutation associated with ultra-mutated status.\n\nCOHORT 8: pMMR\u002FMSS status and KRAS G12C mutation, absence of HER2 overexpression\u002Famplification and wild-type status for BRAF.\n\nCOHORT 9: pMMR\u002FMSS status and absence of of HER2 overexpression\u002Famplification, absence of POLE\u002FD1 proof-read domain pathogenic mutation associated with ultra-mutated status, absence of KRAS G12C mutation.\n\nCOHORT 10: pMMR\u002FMSS status and absence of of HER2 overexpression\u002Famplification, absence of POLE\u002FD1 proof-read domain pathogenic mutation associated with ultra-mutated status, absence of KRAS G12C mutation.\n\nCOHORT 11: pMMR\u002FMSS status and wild-type status for RAS and BRAF, absence of molecular predictors of resistance (PRESSING panel negative except for MET alterations - MET amplifications and mutations are allowed), Left-sided and rectal primary tumor location, according to the specific inclusion criterion regarding rectal tumors.\n\nCOHORT 12: pMMR\u002FMSS status and wild-type status for RAS and BRAF, absence of molecular predictors of resistance (PRESSING panel negative except for MET alterations - MET amplifications and mutations are allowed), Right-sided primary tumor location.\n\nCOHORT 1 of UNICORN part 2 (to enroll sequentially after completion of cohort 10): pMMR\u002FMSS status and absence of molecular characteristics allowing enrollment in cohorts 1,2 and 8 (i.e HER2 overexpression\u002Famplification, POLE\u002FD1 proof-read domain pathogenic mutation associated with ultra-mutated status, absence of KRAS G12C mutation. Patients with tumor characteristics of EGFR dependency (regardless of MET) will be eligible for cohort 1 of UNICORN part 2 only after completion of cohort 11 or 12 (depending on primary tumor sidedness) and upon discussion with the Sponsor\n\nExclusion Criteria:\n\nGeneral exclusion criteria\n\n* Distant metastases at any site, as defined by negativity of chest\u002Fabdomen\u002Fpelvis contrast-enhanced computed tomography (CT).\n* Risk criteria for obstructing disease at radiology or endoscopy as defined in the pivotal FOxTROT study.\n* Need to receive neoadjuvant radiation or chemoradiation in patients with rectal cancer.\n* Patients with known hypersensitivity to the study drug of the assigned cohort or to its excipients or to drugs belonging to the same drug class.\n* Previous or concurrent malignancy within 2 years of study entry.\n* Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following: history of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft, coronary angioplasty or stenting) ≤ 6 months prior to start of study treatment; symptomatic congestive heart failure (i.e., Grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and\u002For conduction abnormality ≤ 6 months prior to start of study treatment, except atrial fibrillation and paroxysmal supraventricular tachycardia.\n* Known history of HIV infection.\n* Active infection including tuberculosis, hepatitis B, hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \\[anti-HBc\\] and absence of HBsAg) are eligible only in case of negativity of HBV DNA. Patients positive for hepatitis C (HCV) antibody are eligible only if PCR is negative for HCV RNA.\n* Other severe acute or chronic diseases that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient an inappropriate candidate for the study.\n* Any psychiatric condition that would prohibit the understanding or rendering of informed consent and that would limit compliance with trial requirements.\n* Women in pregnancy or lactation condition. Women with child-bearing potential or sexually-active men not willing to use adequate contraception during whole study period.\n* Use of any disallowed drugs.\n\nSpecific exclusion criteria for each Cohort:\n\nCOHORT 1:\n\n* Previous treatment with a DXd-containing ADC or any anti-HER2 agent.\n* Has LVEF\\\u003C 50% within 28 days before enrolment.\n* Has a history of (non-infectious) ILD\u002Fpneumonitis that required steroids, has current ILD\u002Fpneumonitis, or where suspected ILD\u002Fpneumonitis cannot be ruled out by imaging at Screening. (eg, pulmonary emboli within 3 months of the enrolment, severe asthma, severe chronic obstructive pulmonary disease \\[COPD\\], restrictive lung disease, pleural effusion, etc.).\n* Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the enrolment, severe asthma, severe chronic obstructive pulmonary disease \\[COPD\\], restrictive lung disease, pleural effusion, etc.).\n* Any autoimmune, connective tissue, or inflammatory disorders where there is documented, or a suspicion of, pulmonary involvement at the time of Screening.\n* Prior pneumonectomy.\n* Has substance abuse or any other medical conditions that may interfere with the subject's participation in the clinical study or evaluation of the clinical study results.\n* Patients with a medical history of myocardial infarction within 6 months before randomization\u002Fenrolment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrollment to rule out myocardial infarction.\n* Corrected QT interval (QTcF) prolongation to \\> 470 msec (females) or \\>450 msec (males) based on average of the screening triplicate12-lead ECG.\n* A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).\n\nCOHORT 2, 4, 5, 6, 7, 10 and Cohort 1 of UNICORN part 2:\n\n* History of autoimmune diseases or history of bone marrow or organ transplantation that requires immunosuppressive therapy.\n* History of active primary immunodeficiency.\n* Any condition requiring systemic treatment with corticosteroids at doses equal or superior to 10 mg daily of prednisone or equivalents, or other immunosuppressive drugs within 14 days from the inclusion in the study.\n* Administration of live vaccines within 4 weeks from the inclusion in the study. Note: patients, if enrolled, should not receive live vaccine while receiving study drug(s) and up to 30 days after the last dose of study drug(s).\n* Prior treatment with anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents.\n\nCOHORT 3 and 8\n\n* History of interstitial lung disease (e.g. pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan.\n* Magnesium below the LNL.\n* Prior treatment with an EGFR inhibitor.\n\nCOHORT 8:\n\n* Patients who are unable to take a drug by mouth or previous clinical conditions or surgical resection that may affect the absorption of the study drug.\n* Use of CYP3A4 or P-gp substrates with a narrow therapeutic window within 14 days or 5 half-lives of the drug or its major active metabolite, whichever is longer.\n* Use of any herbal medications\u002Fsupplements.\n* Tumors with KRAS, NRAS, HRAS, BRAF or PTPN11 (SHP2) mutations, except KRAS G12C.\n* Prior treatment with a KRAS G12C inhibitor.\n\nCOHORT 9 and 10:\n\n* Prior treatment with EP4 receptor antagonists.\n* Inability to swallow medications.\n* Presence of portal hypertension and\u002For oesophageal varices.\n* Known severe gastritis, duodenal or gastric ulcer, or any other condition that may lead to bleeding or perforation.\n\nCOHORTS 11 and 12:\n\n* Prior treatment with an anti-EGFR and\u002For MET inhibitor.\n* History of interstitial lung disease (e.g. pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan\n* Clinically active infectious liver disease\n* Any ophthalmologic condition that is clinically unstable",{"count":51,"type":21},197,[24],"This is a window-of-opportunity umbrella platform trial enrolling non-metastatic resectable colorectal patients selected for the presence of a specific targetable molecular alteration. The study aims to test the activity of specific targeted agents\u002Fcombinations given as a short-course pre-operative strategy, matched with the specific alteration detected, followed by standard of care surgery.",[55,56],"Colorectal Cancer","Resectable Colorectal Carcinoma",[58,59,60],"targeted treatment","molecular alterations","platform trial","2026-03-10",{"date":63,"type":34},"2026-03-12",{"date":65,"type":34},"2023-05-11",{"date":67,"type":21},"2028-05",{"name":40,"class":41},{"id":70,"slug":71,"hasResults":11,"nctId":72,"briefTitle":73,"officialTitle":74,"acronym":75,"eligibilityCriteria":76,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":77,"targetDuration":4,"studyType":22,"phases":79,"briefSummary":80,"conditions":81,"keywords":88,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":95,"lastUpdatePostDateStruct":96,"startDateStruct":98,"completionDateStruct":100,"leadSponsor":102,"locationsCount":103},"100624271","phase-2-upfront-trastuzumab-deruxtecan-plus-capecitabine-and-bevacizumab-for-patients-with-her-2-positive-metastatic-colorectal-cancer-100624271","NCT07407465","Upfront Trastuzumab-Deruxtecan Plus Capecitabine and Bevacizumab for Patients With HER-2 Positive Metastatic Colorectal Cancer.","Phase II Single Arm Study of Upfront Trastuzumab-Deruxtecan Plus Capecitabine and Bevacizumab for Patients With HER-2 Positive Metastatic Colorectal Cancer: the CHIMERA Study.","CHIMERA","Inclusion Criteria:\n\n* Written informed consent obtained from the patient\u002Flegal representative before performing any protocol-related procedures, including screening evaluations.\n* Patient state to comply with all the study procedures and treatments. Patients must be accessible for treatment and follow-up. Patients registered for this trial must be treated and followed at the participating Centre.\n* Age ≥ 18 years at the time of informed consent.\n* ECOG Performance Status ≤ 2.\n* Life expectancy of ≥ 3 months.\n* Have histologically documented adenocarcinoma of the colon or rectum, which is initially metastatic or unresectable locally advanced.\n* Subjects must be willing to provide the most recently available formalin-fixed paraffin-embedded tumor tissue blocks (or at least 25 freshly sectioned slides) for translational analyses (sampled before 1st treatment course). If archival tissue is not available for HER2 testing or for exploratory aims, then a newly obtained baseline biopsy of an accessible tumor lesion is required before Cycle 1 Day 1 timeframe. Biopsy must contain adequate tissue for analysis; the following biopsy types are acceptable: resection, excision, punch (skin lesions only) and core needle biopsies.\n* Presence of locally determined HER2 overexpression\u002Famplification defined as IHC 3+ or 2+\u002FISH amplified on archival\u002Fnewly obtained tumor tissue, according to the American Society of Clinical Oncology\u002FCollege of American Pathologists (ASCO\u002FCAP) guidelines for gastric\u002Fgastroesophageal cancer.\n* Have RAS known status and pMMR\u002FMSS status by standard local testing.\n* Have radiographically measurable disease per RECIST v1.1.\n* Have adequate hematological, hepatic, renal, cardiac and coagulation function, as defined below, obtained ≤ 7 days prior to enrollment (Cycle 1 Day 1):\n\n  * Absolute neutrophil count (ANC) ≥ 1500\u002Fmm3. (Granulocyte-colony stimulating factor administration is not allowed within 1 week prior to C1D1).\n  * Platelet count ≥ 100000\u002Fmm3. (Platelet transfusion is not allowed within 1 week prior to C1D1)\n  * Hemoglobin ≥ 9.0 g\u002FdL\n  * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline.\n  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN (≤ 5 x ULN if liver metastases are present).\n  * Serum albumin ≥ 2.5 g\u002FdL.\n  * Creatinine clearance ≥ 60 mL\u002Fmin as determined by Cockcroft-Gault (using actual body weight).\n  * Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days before enrollment.\n  * International normalized ratio or Prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤ 1.5 x ULN.\n* Have had adequate washout period from previous treatment before screening, defined as:\n\n  * ≥ 4 weeks from major surgery.\n  * ≥ 4 weeks from radiation therapy, including palliative stereotactic radiation therapy to the chest.\n  * ≥ 3 weeks from anti-cancer chemotherapy \\[immunotherapy (non-antibody-based therapy)\\], retinoid therapy, hormonal therapy.\n  * ≥ 4 weeks from antibody-based anti-cancer therapy\n  * ≥ 2 weeks or 5 half-lives (whichever is longer) from targeted agent- and small molecule-based therapy\n  * ≥ 6 weeks from nitrosureas or mitomycin C\n  * ≥ 1 week from TKIs approved for treatment of patients with non-small-cell lung cancer (baseline CT must be completed after discontinuation of TKI)\n  * \\> 2 weeks from chloroquine\u002Fhydroxychloroquine\n  * ≥ 2 weeks from cell-free and Concentrated Ascites Reinfusion Therapy (CART), peritoneal shunt or drainage of ascites, pleural or pericardial effusion.\n* Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner. For women of childbearing potential, a negative result for serum pregnancy test (test must have a sensitivity of at least 25 mIU\u002FmL) must be available at the screening visit and urine beta- human chorionic gonadotropin (β-HCG) pregnancy test prior to each administration of IP. Women of childbearing potential are defined as those who are not surgically sterile (i.e. underwent bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) or post-menopausal. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.\n* Female patients of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception, presented in Table 1. From the time of screening and must agree to continue using such precautions for 7 months after the last dose of investigational product (IP). Not all methods of contraception are highly effective. Female patients must refrain from breastfeeding while on study and for 7 months after the last dose of IP. Complete heterosexual abstinence for the duration of the study and drug washout period is an acceptable contraceptive method if it is line with the patient's usual lifestyle (consideration must be made to the duration of the clinical trial); however, periodic, or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable.\n* Female participants must not donate, or retrieve for their own use, ova from the time of enrolment and throughout the study treatment period, and for at least 7 months after the final study drug administration. They should refrain from breastfeeding throughout this time. Preservation of ova may be considered prior to enrollment in this study.\n* Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to 4 months after the final dose of IP for T-DXd while 6 months for capecitabine and bevacizumab. Complete heterosexual abstinence for the duration of the study and drug washout period is an acceptable contraceptive method if it is in line with the patient's usual lifestyle (consideration must be made to the duration of the clinical trial); however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable. It is strongly recommended for the female partners of a male patient to also use at least one highly effective method of contraception throughout this period, by employing protocol-recommended methods. In addition, male patients should refrain from fathering a child, or freezing or donating sperm from the time of randomization\u002Fenrollment, throughout the study and for 4 months after the last dose of IP for T-DXd while 6 months for capecitabine and bevacizumab. Preservation of sperm should be considered prior to enrollment in this study.\n\nExclusion Criteria:\n\n* Have previously received any systemic anticancer therapy for CRC in the metastatic\u002Flocally advanced unresectable setting or have participated in any interventional clinical trial for CRC in the metastatic\u002Flocally advanced unresectable setting. Subjects may have received prior fluoropyrimidine with or without oxaliplatin for CRC in the adjuvant or neoadjuvant setting if it was completed \\> 6 months before enrollment.\n* Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.\n* Have previously been treated with an anti-HER2 agent and\u002For a topoisomerase I inhibitor.\n* Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medications.\n* Have substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results.\n* Patients with a medical history of myocardial infarction (MI) within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Subjects with troponin levels above ULN at screening (as defined by the manufacturer) and without any myocardial-related symptoms should undergo a cardiologic consultation before enrollment to rule out MI.\n* Corrected QT interval (QTcF) prolongation to \\> 470 msec (females) or \\> 450 msec (males) based on average of the screening 12-lead ECG.\n* Symptomatic arterial hypertension or uncontrolled arterial hypertension, as determined by the investigator.\n* Have a history of (non-infectious) ILD\u002Fpneumonitis that required steroids, have current ILD\u002Fpneumonitis, or where suspected ILD\u002Fpneumonitis cannot be ruled out by imaging at screening.\n* Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g., severe asthma, severe chronic obstructive pulmonary disease \\[COPD\\], restrictive lung disease, pleural effusion, etc.).\n* Any autoimmune, connective tissue, or inflammatory disorders (e.g., Rheumatoid arthritis, Sjögren's, sarcoidosis etc.) where there is documented, or a suspicion of, pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the eCRF for patients who are included in the study.\n* Prior pneumonectomy (complete).\n* A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).\n* Have unresolved toxicities from previous anticancer therapy, defined as toxicity (other than alopecia) not yet resolved to Grade ≤ 1 or baseline. Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to Grade \\> 2 for at least 3 months before enrollment\u002Fcycle 1 day 1 and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy such as: chemotherapy-induced neuropathy and fatigue.\n* Patients with known hypersensitivity to the study drug or to its excipients.\n* Patients with known hypersensitivity to other monoclonal antibodies.\n* Pregnant or breastfeeding female patients, or patients who are planning to become pregnant. Sexually active men not willing to use adequate contraception during whole study period.\n* Previous or concurrent malignancy within 3 years of study entry. Exceptions are adequately resected non-melanoma skin cancer, curatively treated in-situ diseases, and other solid tumors that have been curatively treated.\n* Presence of any of the following dihydropyrimidine dehydrogenase (DPYD) polymorphism, based on local laboratory testing: DPYD 2a (c.1905+1G\\>A); DPYD13 (c.1679 T\\>G); DPYD D949V (c.2846 A\\>T). French and German patients may undergo baseline uracilemia assessment as detailed below in spite of polymorphism testing.\n* Have a history of transient ischemic attack, cerebrovascular accident, myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or cardiac surgery within 6 months prior to enrollment (Cycle 1 Day 1).\n* Have a history of a significant bleeding event (e.g., bleeding needing medical intervention) within 6 months prior to enrollment (Cycle 1 Day 1) unless the source of bleeding has been definitively treated.\n* Have a history of GI perforation within 12 months prior to enrollment (Cycle 1 Day 1).\n* Major surgical procedure or significant traumatic injury ≤ 28 days prior to enrollment (≤ 56 days for hepatectomy, open thoracotomy or major neurosurgery) or anticipation of need for major surgical procedure during the course of the study.\n* Serious, non-healing wound, ulcer, or bone fracture.\n* Prior organ transplantation, including allogenic stem-cell transplantation.\n* Known history of HIV infection.\n* Active infection including tuberculosis, hepatitis B, hepatitis C. Patients positive for hepatitis C (HCV) antibody are eligible only if HCV RNA polymerase chain reaction (PCR) is negative. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \\[anti-HBc\\] and absence of HBsAg) are eligible only if meeting the following criteria:\n\n  * HBsAg negativity (for more than 6 months off anti-viral treatment).\n  * Anti-HBc positivity (IgG or total Ig).\n  * Absence of cirrhosis or fibrosis on prior imaging or biopsy.\n  * Absence of HCV co-infection and no history of HCV co-infection.\n  * Access to a local HBV expert during and after the study Patients meeting all abovementioned criteria must be closely monitored for HBV reactivation.\n* Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of trastuzumab deruxtecan. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IMP\n* Any psychiatric condition that would prohibit the understanding or rendering of informed consent and that would limit compliance with trial requirements.\n* Use of any disallowed drugs (see Section 7.5).\n\nAdditional exclusion criteria for France and Germany:\n\n* Patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency (uracilemia ≥ 16 ng\u002FmL)\n* Patient who is under judicial protection and patient who is legally institutionalized or under guardianship or not able to give consent.",{"count":78,"type":21},42,[24],"The aim of this study is to evaluate the activity of first-line trastuzumab-deruxtecan, capecitabine and bevacizumab in terms of overall response rate for patients with HER-2 positive metastatic\u002Flocally advanced unresectable colorectal cancer",[55,82,83,84,85,86,87],"Colorectal Adenocarcinoma","Rectal Adenocarcinoma","Rectal Cancer, Adenocarcinoma","Rectal Cancer, Metastatic","Colon Cancer Metastatic","Colon Cancer Adenocarcinoma",[89,90,91,92,93,94],"colorectal cancer","HER-2 positive","Trastuzumab-deruxtecan","Capecitabine","Bevacizumab","mCRC","2026-02-15",{"date":97,"type":34},"2026-02-17",{"date":99,"type":34},"2025-10-20",{"date":101,"type":21},"2027-10-20",{"name":40,"class":41},28,{"id":105,"slug":106,"hasResults":11,"nctId":107,"briefTitle":108,"officialTitle":109,"acronym":110,"eligibilityCriteria":111,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":112,"targetDuration":4,"studyType":22,"phases":114,"briefSummary":116,"conditions":117,"keywords":118,"overallStatus":126,"whyStopped":4,"lastUpdateSubmitDate":127,"lastUpdatePostDateStruct":128,"startDateStruct":130,"completionDateStruct":132,"leadSponsor":134,"locationsCount":4},"100600238","phase-4-anti-egfr-agents-in-patients-with-right-sided-advanced-colorectal-cancer-with-wild-type-ras-and-aregereg-high-status-100600238","NCT07094893","Anti-EGFR Agents in Patients With Right-sided Advanced Colorectal Cancer With Wild-type RAS and AREG\u002FEREG High Status","A Biomarker Enrichment Trial of Anti-EGFR Agents in Patients With Advanced Colorectal Cancer (aCRC) With Wild-type RAS and Right Primary Tumour Location (Right-PTL).","ARIEL-ENGIC","Inclusion Criteria for Registration:\n\n* Age ≥18 years\n* Biopsy-confirmed adenocarcinoma of the colon with a right primary tumour location\n* aCRC defined as either M1 or locally inoperable disease\n* Tumour RAS status either wild-type (by local testing) or unknown\n* Fit for combination chemotherapy plus anti-EGFR agent\n* Sufficient tumour material for EREG\u002FAREG analysis\n* Written informed consent for registration\n\nExclusion Criteria for Registration\n\n* Tumour RAS-mutation present\n* Prior chemotherapy for aCRC\n* Prior anti-EGFR agent therapy\n\nInclusion Criteria for Randomisation:\n\n* Registered in ARIEL-ENGIC\n* Local testing confirms tumour RAS-wt status\n* ARIEL-ENGIC central testing confirms tumour EREG\u002FAREG high\n* Tumour measurable by RECIST v1.1 criteria on CT scan\n* Participants have had CT scan within the timeframes stipulated (If there is a contrast reaction, then non-contrast CT with MRI is acceptable, assuming at least one of these modalities shows measurable disease at baseline for ETS evaluation and both modalities are repeated at the trial timepoints at week 8 and 16 and every 8 weeks until disease progression.)\n* Pre-randomisation laboratory tests :\n* Neutrophils ≥1.5 x109\u002Fl and platelet count ≥100 x109\u002Fl\n* Serum bilirubin ≤ 1.25 x upper limit of normal (ULN), alkaline phosphatase\n\n  * 5x ULN, and serum transaminase (either AST or ALT) ≤ 2.5 x ULN\n* Estimated creatinine clearance ≥50ml\u002Fmin (creatinine clearance estimated as per local practice)\n* WHO performance status (PS) 0, 1 or 2\n* Fit for combination chemotherapy plus anti-EGFR agent\n* Life expectancy of at least 12 weeks\n* Women of childbearing potential must have a negative blood pregnancy test at the baseline visit.\n* Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception\n* Written informed consent for randomization.\n\nExclusion Criteria for Randomisation:\n\n* Participant has received more than one cycle of chemotherapy since registration\n* Participants with history of hypersensitivity to any component of their proposed trial treatment regimen or any of their excipients\n* Participants in receipt of live vaccine within four weeks prior to randomisation\n* Participants with a history interstitial pneumonitis\u002Fidiopathic lung disease (ILD) or pulmonary fibrosis\n* Participants with a history of keratitis, ulcerative keratitis or severe dry eye\n* Participants with a history of severe skin reaction which in the clinicians' opinion could be exacerbated by EGFR Mab (cf Steven's Johnson Syndrome)\n* Complete dihydropyrimidine dehydrogenase (DPYD) deficiency\n* Untreated brain metastases or spinal cord compression or primary brain tumours\n* History or evidence upon physical examination of CNS disease unless adequately treated\n* Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration\n* Clinically significant (e.g. active) cardiovascular disease for example cerebrovascular accidents, myocardial infarction, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF), serious cardiac arrhythmia requiring medication\n* Treatment with any investigational drug within 30 days prior to enrolment or 2 investigational agent half-lives (whichever is longer)\n* Other co-existing malignancies or malignancies diagnosed within the last 5 years that are likely to have an impact upon survival or treatment delivery\n* Known human immunodeficiency virus (HIV)\n* Has documented presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to enrolment\n* Has a positive hepatitis C virus (HCV) antibody test result at screening or within 3 months prior to enrolment. Note: Participants with a positive HCV antibody test result due to prior resolved disease can be randomised, only if a confirmatory HCV RNA test is obtained - Definite contraindications for the use of corticosteroids and antihistamines as premedication.\n* Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies.\n* Woman pregnant or lactating or expecting to conceive children within the projected duration of the study through 6 months after the last dose of bevacizumab and\u002For fluorouracil.",{"count":113,"type":21},280,[115],"PHASE4","The aim of this trial is to assess the feasibility of EREG\u002FAREG assessment as a clinical diagnostic standard, used to guide clinical decision making in right-PTL, RAS-wt aCRC. Further to this, the aim is to determine whether EREG\u002FAREG status identifies right-PTL participants who will benefit from the addition of anti-EGFR therapy to first-line chemotherapy.",[55],[119,120,121,122,123,124,125],"metastatic colorectal cancer","first-line","right primary tumour location","AREG","EREG","RAS wild-type","anti-EGFR","NOT_YET_RECRUITING","2026-01-13",{"date":129,"type":34},"2026-01-14",{"date":131,"type":21},"2026-04-15",{"date":133,"type":21},"2030-03",{"name":40,"class":41},{"id":136,"slug":137,"hasResults":11,"nctId":138,"briefTitle":139,"officialTitle":140,"acronym":141,"eligibilityCriteria":142,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":143,"enrollmentInfo":144,"targetDuration":4,"studyType":22,"phases":146,"briefSummary":148,"conditions":149,"keywords":150,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":156,"lastUpdatePostDateStruct":157,"startDateStruct":159,"completionDateStruct":161,"leadSponsor":163,"locationsCount":164},"100572420","phase-3-folfoxiri-plus-bevacizumab-with-or-without-atezolizumab-as-1st-line-treatment-of-pmmr-and-is-ic-high-metastatic-colorectal-cancer-patients-100572420","NCT06733038","FOLFOXIRI Plus Bevacizumab With or Without Atezolizumab as 1st Line Treatment of pMMR and IS IC-High Metastatic Colorectal Cancer Patients.","Phase III Randomized Study of FOLFOXIRI Plus Bevacizumab and Atezolizumab Versus FOLFOXIRI Plus Bevacizumab as First-Line Treatment of Unresectable pMMR and Immunoscore IC-High Metastatic Colorectal Cancer Patients","AtezoTRIBE2","Inclusion Criteria:\n\n* Histologically proven diagnosis of colorectal cancer;\n* Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease;\n* Proficient mismatch repair (pMMR) status in tumour tissue (primary or metastatic), as determined by a local laboratory assay in a CLIA- or similarly certified;\n* Immunoscore IC-high status in tumour tissue (primary or metastatic), as determined by a sponsor-defined central laboratory (HEGP, AP-HP, INSERM, France).\n* At least one measurable lesion according to RECIST criteria (version 1.1);\n* Availability of adequate tumour specimen (primary or metastatic);\n* Male or female of 18-75 years of age;\n* ECOG PS ≤ 2 if aged \\\u003C 71 years, ECOG PS = 0 if aged 71-75 years;\n* Life expectancy of at least 12 weeks;\n* Previous adjuvant chemotherapy allowed only if with fluoropyrimidine monotherapy and more than 6 months elapsed between the end of adjuvant and first relapse;\n* Neutrophils \\>1.5 x 109\u002FL, Platelets \\>100 x 109\u002FL, Hb \\>9 g\u002Fdl;\n* Total bilirubin ≤1.5 times the upper-normal limits (UNL) of the normal values and AST (SGOT) and\u002For ALT (SGPT) \\\u003C2.5 x UNL (or \\\u003C5 x UNL in case of liver metastases) alkaline phosphatase \\\u003C2.5 x UNL (or \\\u003C5 x UNL in case of liver metastases);\n* Creatinine clearance ≥50 mL\u002Fmin or serum creatinine ≤1.5 x UNL;\n* INR or aPTT ≤1.5 x ULN. This applies only to patients who are not receiving therapeutic anticoagulation;\n* Urine dipstick of proteinuria \\\u003C2+. Patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate ≤1 g of protein\u002F24 h;\n* Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient;\n* 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 (barrier contraceptive measure or oral contraception) and outlined in \"Section 6.5 - Contraception\", starting with the first dose of study therapy through 6 months after the last dose of bevacizumab and fluorouracil and within 5 months after the last dose of atezolizumab.\n* Females of childbearing potential must have a negative blood pregnancy test at the baseline visit (i.e., performed maximum 7 days before the treatment start);\n* Will and ability to comply with the protocol;\n* Written informed consent to study procedures.\n\nExclusion Criteria:\n\n* Radiotherapy to any site within 4 weeks before the study;\n* Previous adjuvant oxaliplatin-containing chemotherapy;\n* Previous treatment with bevacizumab;\n* Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents;\n* Complete dihydropyrimidine dehydrogenase (DPYD) deficiency (homozygous of the following DPYD polymorphisms: c1679GG, c1905+1AA, c2846TT);\n* Untreated brain metastases or spinal cord compression or primary brain tumours;\n* History or evidence upon physical examination of CNS disease unless adequately treated;\n* History of haemoptysis ≥ 2 grade NCIC-CTG criteria within one month prior to screening;\n* Active or untreated CNS metastases:\n* Symptomatic peripheral neuropathy \\> 2 grade NCIC-CTG criteria;\n* Serious, non-healing wound, ulcer, or bone fracture;\n* Evidence of bleeding diathesis or coagulopathy;\n* Uncontrolled hypertension (SBP\\>150 mmHg and\u002For DPB\\>100 mmHg), or prior history of hypertensive crisis, or hypertensive encephalopathy ;\n* Clinically significant (i.e., active) cardiovascular disease for example cerebrovascular accidents (within 6 months prior to study enrollment), myocardial infarction (within 6 months prior to study enrollment), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication;\n* Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of study enrolment;\n* Active infection requiring antibiotics at the time of initiation of study treatment;\n* Any previous venous thromboembolism ≥ NCI CTCAE Grade 4;\n* History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment;\n* Current or recent (within 10 days prior to study treatment start) ongoing treatment with full-dose anticoagulants for therapeutic purposes.\n* Chronic, daily treatment with high-dose aspirin (\\>325 mg\u002Fday);\n* Treatment with any investigational drug within 30 days prior to enrollment or 2 investigational agent half-lives (whichever is longer);\n* Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ;\n* 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;\n* Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to initiation of study treatment;\n* Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication;\n* Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last dose of bevacizumab, fluorouracil and within 5 months after the last dose of atezolizumab;\n* History of autoimmune disease;\n* History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan;\n* Positive test for human immunodeficiency virus (HIV);\n* Active hepatitis B (defined as having a positive hepatitis B surface antigen \\[HBsAg\\] test prior to randomization) or hepatitis C;\n* Active tuberculosis;\n* Prior allogenic bone marrow transplantation or solid organ transplant;\n* Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumour necrosis factor \\[TNF\\] agents) within 2 weeks prior to start of study treatment, or requirement for systemic immunosuppressive medications during the trial. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed;\n* Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of the atezolizumab formulation;\n* Administration of a live, attenuated vaccine within 4 weeks prior to start of study treatment or anticipation that such a live attenuated vaccine will be required during the study;\n* Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is longer, prior to start of study treatment; • If receiving a RANKL inhibitor (e.g. denosumab), unwilling to adopt alternative treatment such as (but not limited to) bisphosphonates, while receiving atezolizumab.","75 Years",{"count":145,"type":21},238,[147],"PHASE3","The aim of this study is to evaluate the efficacy of the addition of Atezolizumab to FOLFOXIRI plus bevacizumab as first line treatment of patients with pMMR and Immunoscore IC-high metastatic colorectal cancer in terms of Progression Free Survival (PFS).",[55],[151,152,119,153,154,155],"atezolizumab","FOLFIXIRI\u002Fbevacizumab","pMMR\u002FMSS","IMMUSCORE IC-High","first line","2025-12-05",{"date":158,"type":34},"2025-12-08",{"date":160,"type":34},"2024-11-15",{"date":162,"type":21},"2029-04-01",{"name":40,"class":41},24,{"id":166,"slug":167,"hasResults":11,"nctId":168,"briefTitle":169,"officialTitle":170,"acronym":171,"eligibilityCriteria":172,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":173,"targetDuration":4,"studyType":22,"phases":175,"briefSummary":176,"conditions":177,"keywords":179,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":186,"lastUpdatePostDateStruct":187,"startDateStruct":189,"completionDateStruct":191,"leadSponsor":193,"locationsCount":103},"100585075","phase-3-gemcitabine-plus-nab-paclitaxel-as-switch-maintenance-versus-continuation-of-modified-folfirinox-as-1st-line-chemotherapy-in-patients-with-advanced-pancreatic-cancer-100585075","NCT06897644","Gemcitabine Plus Nab-paclitaxel as Switch Maintenance Versus Continuation of Modified FOLFIRINOX as 1st Line Chemotherapy in Patients With Advanced Pancreatic Cancer.","Gemcitabine Plus Nab-PAclitaxel as Switch maiNTEnance Versus cONtinuation of Modified FOLFIRINOX as First-line Chemotherapy in Patients With Advanced Pancreatic Cancer: the PANThEON Phase III Trial","PANThEON","Inclusion Criteria:\n\n* Patient able and willing to provide written informed consent and to comply with the study protocol.\n* Subjects must be ≥18 years.\n* Histologically or cytologically confirmed unresectable locally advanced or metastatic pancreatic adenocarcinoma eligible for treatment in the first-line setting.\n* Presence of measurable or non-measurable disease assessed by CT scan and\u002For MRI according to RECIST 1.1. Note: any lesion which has been subjected to percutaneous therapies or radiotherapy should not be considered measurable, unless the lesion has clearly progressed since the procedure.\n* Availability of archival tumor sample (primary tumor or metastatic site) for biomarker analysis.\n* ECOG performance status of 0-1 (if age \\\u003C 70 years). If age ≥70 years, ECOG PS must be 0.\n* Estimated life expectancy \\> 3 months.\n* Adequate baseline hematologic function characterized by the following at screening:\n\n  * Absolute Neutrophil Count (ANC) ≥ 1.5 × 109\u002FL.\n  * Platelets count ≥ 100 × 109\u002FL.\n  * Hemoglobin ≥ 9 g\u002Fdl. Note: prior transfusions for patients with low hemoglobin are allowed.\n* Adequate liver function characterized by the following at screening:\n\n  * Serum total bilirubin ≤ 1.5 × ULN and \\\u003C 2 mg\u002FdL. Note: Subjects with Serum total bilirubin ≥ 1.5 × ULN and conjugated bilirubin ≤ ULN or \\\u003C 40% of total bilirubin are allowed.\n  * Serum transaminases (AST and\u002For ALT) \\\u003C 3 x ULN (\\\u003C 5 x ULN in presence of liver metastasis). In participants with elevated AST or ALT, the values must be stable for at least 2 week and with no evidence of biliary obstruction by imaging.\n* Adequate renal function, i.e. serum creatinine ≤ 1.5 x institutional ULN and calculated by Cockroft-Gault formula or directly measured creatinine clearance ≥ 50 mL\u002Fmin.\n* Adequate coagulation functions as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy).\n* No presence of complete dihydropyrimidine dehydrogenase (DPYD) enzyme deficiency (homozygous of the following DPYD polymorphisms: c1679GG, c1905+1AA, c2846TT) with DPYD gene testing mandatory at screening as per national guidelines. UDP-glucuronosyltransferase 1A1 (UGT1A1) testing is not mandatory. However, if UGT test is routinely performed in the participating centers, enrolment of patients carriers of variants of DPYD and homozygous variant UGT1A1 \\[7\u002F7\\] has to be discussed with the Sponsor.\n* Women of childbearing potential must agree to remain abstinent (refrain from sexual intercourse) or use highly effective contraceptive methods, as defined in APPENDIX V of the full protocol, during the treatment period and for at least 7 months after the last administration of study treatments.\n* Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women \\\u003C1 year after the onset of menopause.\n* Men must agree to remain abstinent (refrain from sexual intercourse) or use highly effective contraceptive methods during the treatment period and for at least 7 months after the last administration of study treatments.\n* Participants must agree not to donate eggs\u002Fsperm for future use for the purposes of assisted reproduction during the study and for a period of 7 months after receiving the last dose of study treatment. Female and male participants should consider preservation of eggs\u002Fsperm prior to study treatment as anti-cancer treatments may impair fertility.\n\nExclusion Criteria:\n\n* Pancreatic neuroendocrine, acinar, squamous\u002Fadenosquamous, or islet tumors.\n* Previous or concurrent systemic (e.g. cytotoxic or targeted or other experimental drugs) therapy for advanced pancreatic adenocarcinoma.\n\nNote: previous (neo)adjuvant or perioperative anti-cancer therapy for non-metastatic, resectable or borderline resectable PDAC, associated with surgery on the primary tumor, is allowed if \\> 9 months have elapsed from the last dose of therapy and documented disease progression or relapse.\n\n* Major surgery or radiation therapy performed within \\\u003C4 weeks before randomization. Palliative radiotherapy to bone lesions is allowed if performed \\> 2 weeks prior to start of study treatment. Patients must have recovered from an effect from major surgery.\n* Known allergy or hypersensitivity to study drugs and\u002For their excipients.\n* Unresolved toxicity ≥ CTCAE grade 2 attributed to any prior therapies (e.g. grade ≥2 peripheral neurotoxicity), excluding anemia or alopecia.\n* Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that requires directed therapy (such as radiotherapy or surgery) or increasing doses of corticosteroids 2 weeks prior to study entry. Participants with treated symptomatic brain metastases should be neurologically stable for 4 weeks post-treatment and prior to study entry.\n* Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years prior to study entry except for curatively treated basal cell carcinoma of the skin, in situ carcinoma of the cervix, and prostate cancer.\n* Know active uncontrolled hepatitis B or hepatitis C. Patients with a past or resolved HBV infection are eligible. Patients with chronic disease controlled by antiviral therapy or requiring prophylactic treatment are eligible.\n* Chronic or current active infectious disease requiring systemic antibiotics or antifungal treatment within 2 weeks prior to enrollment.\n* Known uncontrolled HIV infection. HIV-positive patients are eligible if their CD4+ cell count amounts to 300 cells per μL or more; HIV viral load must be undetectable per standard of care assay, and patients must be compliant with antiretroviral treatment.\n* Pregnant or breast-feeding patient, or patient planning to become pregnant within 7 months after the end of treatment.\n* Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA \\> II, unstable angina pectoris, history of myocardial infarction within 3 months before study entry, significant arrhythmia).\n* Presence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent.\n* Any serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial.",{"count":174,"type":21},340,[147],"PANThEON is a randomized, open-label, multicenter phase III trial aimed at comparing the switch maintenance with gemcitabine plus nab-paclitaxel (ARM B) versus mFOLFIRINOX continuation (ARM A) in terms of overall survival (OS) in patients with unresectable LAD or mPDAC without disease progression following 3 months of induction mFOLFIRINOX triplet chemotherapy.",[178],"Pancreatic Adenocarcinoma Advanced or Metastatic",[155,180,181,182,183,184,185],"mFOLFIRINOX","chemotherapy","pancreas","Gemcitabine with Nab-Paclitaxel","switch maintenance","pancreatic cancer","2025-05-23",{"date":188,"type":34},"2025-05-25",{"date":190,"type":34},"2025-03-27",{"date":192,"type":21},"2030-01-01",{"name":40,"class":41},{"id":195,"slug":196,"hasResults":11,"nctId":197,"briefTitle":198,"officialTitle":199,"acronym":200,"eligibilityCriteria":201,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":202,"targetDuration":4,"studyType":22,"phases":204,"briefSummary":205,"conditions":206,"keywords":210,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":219,"lastUpdatePostDateStruct":220,"startDateStruct":222,"completionDateStruct":224,"leadSponsor":226,"locationsCount":227},"100582911","phase-2-cetuximab-plus-platinum-and-taxane-based-chemotherapy-followed-by-avelumab-and-cetuximab-as-first-line-treatment-for-recurrentmetastatic-head-and-neck-squamous-cell-carcinoma-hnscc-patients-with-a-pd-l1-combined-positive-score-cps119-100582911","NCT06869473","Cetuximab Plus Platinum and Taxane-based Chemotherapy, Followed by Avelumab and Cetuximab, as First-line Treatment for Recurrent\u002FMetastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Patients With a PD-L1 Combined Positive Score (CPS)≥1≤19.","A Single-arm Phase II Study of Cetuximab Plus Platinum and Taxane-based Chemotherapy Followed by AVElumab and Cetuximab as First-line Therapy for Recurrent\u002FMetastatic (R\u002FM) Head and Neck Squamous Cell Carcinoma (HNSCC) Patients With PD-L1 Combined Positive Score (CPS)≥1≤19: the Immunotherapy Sequenc","AVEC-119","Inclusion Criteria:\n\n1. Subjects able to sign the informed consent and ≥18 y-old.\n2. Histologically or cytologically confirmed diagnosis of HNSCC.\n3. Confirmed R\u002FM HNSCC (i.e. oral cavity, oropharynx, larynx, hypopharynx) not suitable for curative loco-regional therapy.\n4. PD-L1 CPS≥1≤19 (assessment allowed either on primary and\u002For recurrent\u002Fmetastatic site of disease).\n5. Measurable disease according to RECIST Criteria 1.1.6. Subjects should not have had prior systemic therapy administered in the R\u002FM HNSCC setting.\n\n7.Systemic therapy that was completed more than 6 months prior to signing consent, if given as a part of multimodal curative treatment for locally advanced disease, is allowed.\n\n8.ECOG Performance Status (PS) 0-1. 9.Adequate bone marrow function: neutrophils ≥ 1.5 x 109\u002FL, platelets ≥ 100 x 109\u002FL, hemoglobin ≥ 9 g\u002FdL.\n\n10.Adequate liver function: total bilirubin level \\\u003C 1.5 X Upper Limit of Normal (ULN) (except for known medical reason not interfering with liver function, such as Gilbert syndrome), AP, GGT \\\u003C3 x ULN and AST and ALT levels ≤ 2.5 × ULN.\n\n11.Adequate renal function: calculated or analyzed creatinine clearance ≥ 30 mL\u002Fmin.\n\n12.Archival or fresh tissue of primary disease (i.e. T and\u002For N and\u002For M) OR recurrent\u002Fmetastatic disease available at baseline (before starting TPE) (available as Formalin-Fixed Paraffin-Embedded - FFPE - or as unstained 10-20 slices).\n\n13.Participants have to provide peripheral blood samples (at least 8-10 mL stored in EDTA) according the timing described in the translational part of the current protocol.\n\n14.Palliative radiotherapy and\u002For surgery within 4 weeks before the study entry are allowed.\n\n15.Symptomatic peripheral neuropathy NCI-CTC v5.0 grade ≥ 2 and \u002F or ototoxicity grade ≥ 2, (except for cases in which ototoxicity is due to trauma or tumor-related mechanical impairment) or creatinine clearance \\\u003C 60 mL\u002Fmin are acceptable and they must be approached with carboplatin (instead of cisplatin) since the trial start.\n\nExclusion criteria:\n\n1. Nasopharyngeal, salivary gland, nasal sinus, and non-melanoma skin cancers are not allowed.\n2. Life expectancy lower than 3 months according to the judgement of trial investigator is not allowed.\n3. Previous chemotherapy, or biological therapy (i.e. Cetuximab), or immunotherapy administered for R\u002FM setting of HNSCC is not allowed.\n4. Diagnosis of immunodeficiency or subjects receiving systemic steroid therapy (\\> 10 mg\u002Fday of prednisone or equivalent) or any other form of immunosuppressive therapy within 30 days prior to start of study treatment which cannot be interrupted.\n5. Known allergic\u002Fhypersensitivity reaction to investigational products or any component in their formulations.\n6. Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).\n7. Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with type I diabetes, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.\n8. Any diagnosed and\u002For treated additional malignancy within 5 years before the study entry with the exception of: curatively treated basal cell carcinoma of the skin, curatively treated squamous cell carcinoma of the skin, curatively treated prostate cancer, curatively resected in situ cervical cancer, and curatively resected in situ breast cancer.\n9. Subjects with a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subjects' participation for the full duration of the trial, or is not in the best interest of the subject to participate, according to the opinion of the treating investigator.\n10. Significant neurologic or known psychiatric or substance abuse disorders that would interfere with cooperation and the requirements of the trial.\n11. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident\u002Fstroke (≤6 months prior to enrollment), myocardial infarction (≤6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.\n12. Prior organ transplantation including allogenic stem-cell transplantation.\n13. Active uncontrolled infection requiring systemic therapy (i.e. I.V. antibiotics).\n14. Known history of testing positive for HIV or known acquired immunodeficiency syndrome.\n15. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening tests positive).\n16. Live vaccination within 30 days of planned start of study treatment (inactivated vaccines are allowed).\n17. Pregnancy (absence of pregnancy must be confirmed by negative serum or urine pregnancy test - ß-HCG - for women of childbearing potential) and\u002For breast-feeding are not allowed. Subjects of childbearing potential willing to use effective contraceptive method \\[Pearl Index \\\u003C 1; e.g. oral contraceptive (pill), hormone spiral, hormone implant, transdermal patch, a combination of two barrier methods (condom and diaphragm), sterilization, sexual abstinence\\] for the entire study duration and 30 days post-dosing.",{"count":203,"type":21},67,[24],"This phase II interventional clinical trial aims to evaluate whether combining cetuximab and avelumab, after three cycles of platinum and taxane-based chemotherapy, can improve treatment outcomes for patients with recurrent or metastatic (R\u002FM) head and neck squamous cell carcinoma (HNSCC) with a PD-L1 combined positive score (CPS) between 1 and 19. Specifically, the study seeks to determine if this approach can increase the 6-month progression-free survival (PFS) rate from 40% to 55%.\n\nThe trial will include adult patients with confirmed R\u002FM HNSCC, who have not previously received systemic therapy for their advanced disease. By testing this sequential treatment strategy, researchers hope to improve outcomes for this specific patient population, which has shown poorer responses to existing immunotherapy options compared to those with higher PD-L1 expression levels.\n\nParticipants will first undergo an induction phase, consisting of three cycles of chemotherapy with paclitaxel, platinum (cisplatin or carboplatin), and cetuximab. After this initial treatment, they will move to a maintenance phase, where they will receive avelumab and cetuximab every two weeks until disease progression or the occurrence of unacceptable side effects.\n\nThe study aims to answer several key questions:\n\nCan this treatment approach improve progression-free survival at 6 months? What impact does it have on overall survival, response rates, and the duration of response? Is this combination therapy safe and well-tolerated? In addition to the treatment itself, participants will be asked to provide blood and tumor tissue samples for translational research, helping scientists better understand how biomarkers influence treatment response. Regular follow-up assessments will also be conducted to monitor disease progression and overall health.\n\nBy testing this innovative treatment sequence, researchers hope to bridge the gap between different PD-L1 subgroups, potentially offering a more effective and personalized approach for patients with R\u002FM HNSCC.",[207,208,209],"Head and Neck Squamous Cell Carcinoma (HNSCC)","Recurrent Head and Neck Cancer","Metastatic Head and Neck Cancer",[211,212,213,214,215,216,217,218],"Head and Neck Neoplasms","Squamous Cell Carcinoma","Cetuximab","Avelumab","Anti-EGFR Therapy","Platinum-Based Chemotherapy","Taxane-Based Chemotherapy","PD-L1 Combined Positive Score (CPS)","2025-03-12",{"date":221,"type":34},"2025-03-14",{"date":223,"type":34},"2025-02-20",{"date":225,"type":21},"2028-02-20",{"name":40,"class":41},8,{"id":229,"slug":230,"hasResults":11,"nctId":231,"briefTitle":232,"officialTitle":233,"acronym":234,"eligibilityCriteria":235,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":143,"enrollmentInfo":236,"targetDuration":4,"studyType":22,"phases":238,"briefSummary":239,"conditions":240,"keywords":243,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":247,"lastUpdatePostDateStruct":248,"startDateStruct":250,"completionDateStruct":252,"leadSponsor":254,"locationsCount":255},"100519010","phase-2-cisplatin-plus-gemcitabine-and-nabpaclitaxel-gap-as-preoperative-chemotherapy-versus-immediate-resection-in-patients-with-resectable-biliary-tract-cancers-btc-at-high-risk-for-recurrence-100519010","NCT06037980","CisPlatin plUs Gemcitabine and Nabpaclitaxel (GAP) as pReoperative Chemotherapy Versus Immediate Resection in patIents With resecTable BiliarY Tract Cancers (BTC) at High Risk for Recurrence","A Phase II\u002FIII Randomized Clinical Trial of CisPlatin plUs Gemcitabine and Nabpaclitaxel (GAP) as pReoperative Chemotherapy Versus Immediate Resection in patIents With resecTable BiliarY Tract Cancers (BTC) at High Risk for Recurrence: PURITY Study","PURITY","Inclusion Criteria:\n\n1. Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures.\n2. Female and male patients ≥18 years and \\\u003C75 years.\n3. Histologically or cytologically confirmed non metastatic resectable carcinoma of biliary tract (BTC), including gallbladder carcinoma (GBC), intrahepatic, periperihilar or distal Cholangiocarcinoma (CCA). Mixed tumor entities with hepatocellular carcinoma and ampullary cancers are excluded.\n4. Availability of a tumoral sample\n5. ECOG performance status of 0-1.\n6. No prior tumor resection for BTC.\n7. Exclusion of distant metastases by CT or MRI of abdomen, pelvis, and thorax and PET scan.\n8. Technically resectable BTC as per local Multidisciplinary Team (MDT) assessment, including a core team with at least one medical oncologist, one surgeon, one radiologist, one endoscopist\u002Fgastroenterologist and one pathologist, all with expertise \\> 3 years on biliary tract cancer and hepatobiliary oncology.\n9. High risk for recurrence defined as the presence of at least one of the following risk features, as evaluated at baseline (pre-surgery):\n\n   1. For cholangiocarcinoma:\n\n      * Suspected or definite locoregional lymph node involvement (at least one of the following):\n\n        * positive FNA cytology (obtained by EUS).\n        * positive locoregional lymph nodes at PET-CT.\n        * suspected positive locoregional lymph nodes at imaging (CT or MRI scan) according to local MDT discussion (eg. short axis \\> 1.5 cm, contrast enhancement uptake, round shape, restriction at DWI).\n      * Macrovascular invasion at preoperative CT scan.\n      * Expected R1 resection due to proximity to major intrahepatic vascular and biliary structures.\n      * For iCCA, presence of satellitosis or multifocal disease or radiological suspicion of tumoral diaphragmatic adhesion.\n      * For iCCA, size of the liver lesion \\>5 cm.\n      * For eCCA, size of the primary lesion \\> 3cm.\n      * Ca19.9 \\>100 U\u002FmL.\n   2. For GBC:\n\n      * Incidentally Detected Gallbladder Carcinoma (IGBC) after simple cholecystectomy with indication for radical second surgery (\\>pT2) or newly diagnosed GBC.\n10. Estimated life expectancy \\> 3 months.\n11. Adequate baseline hematologic function characterized by the following at screening:\n\n    1. ANC ≥ 1.5 × 109\u002FL\n    2. platelets ≥ 100 × 109\u002FL\n    3. hemoglobin ≥ 9 g\u002Fdl. Note: prior transfusions for patients with low hemoglobin are allowed.\n12. Adequate liver function characterized by the following at screening:\n\n    1. Serum total bilirubin ≤ 1.5 × ULN and \\\u003C 2 mg\u002FdL. Note: Subjects with Serum total bilirubin ≥ 1.5 × ULN and conjugated bilirubin ≤ ULN or \\\u003C 40% of total bilirubin are allowed.\n    2. Serum transaminases (AST and\u002For ALT) \\\u003C 3 x ULN.\n13. Adequate renal function, i.e. serum creatinine ≤ 1.5 x institutional ULN and calculated by Cockroft-Gault formula or directly measured creatinine clearance ≥ 50 mL\u002Fmin\n14. Adequate coagulation functions as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy).\n15. No presence of complete dihydropyrimidine dehydrogenase (DPD) enzyme deficiency with DPYD gene testing mandatory at screening as per national guidelines\n16. Females of childbearing potential must agree to remain abstinent (refrain from sexual intercourse) or use highly effective contraceptive methods, as defined in APPENDIX V of the full protocol, during the treatment period and for at least 7 months after the last administration of study treatments.\n17. Males must agree to remain abstinent (refrain from sexual intercourse) or use highly effective contraceptive methods, as defined in APPENDIX V of the full protocol.\n18. Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women \\\u003C1 year after the onset of menopause.\n19. A participant must agree not to donate eggs\u002Fsperm for future use for the purposes of assisted reproduction during the study and for a period of 7 months after receiving the last dose of study treatment. Female and male participants should consider preservation of eggs\u002Fsperm prior to study treatment as anti-cancer treatments may impair fertility.\n\nExclusion Criteria:\n\n1. Known allergy or hypersensitivity to any of the study drugs.\n2. Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry except for curatively treated basal cell carcinoma of the skin, in situ carcinoma of the cervix, and prostate cancer.\n3. Locally unresectable tumor according to local MDT (including radiological evidence suggesting inability to resect with curative intent whilst maintaining adequate vascular inflow and outflow, and sufficient future liver remnant).\n4. Evidence of distant metastases at any site.\n5. Tumors requiring multi-step surgical procedures such as two-stage hepatectomy or Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS) due to liver volumetry-based assessment of anticipated inadequate future liver remnant.\n6. Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic decompensation in the year before enrolment.\n7. Know active uncontrolled hepatitis B or hepatitis C. Patients with a past or resolved HBV infection are eligible. Patients with chronic disease controlled by antiviral therapy or requiring prophylactic treatment are eligible.\n8. Chronic or current active infectious disease requiring systemic antibiotics or antifungal treatment within 2 weeks prior to enrollment.\n9. Known uncontrolled HIV infection. HIV-positive patients are eligible if their CD4+ cell count amounts to 300 cells per μL or more; HIV viral load must be undetectable per standard of care assay, and they must be compliant with antiretroviral treatment.\n10. Pregnant or breast-feeding patient, or patient is planning to become pregnant within 7 months after the end of treatment.\n11. Any other concurrent antineoplastic treatment including radiotherapy.\n12. Previous or concurrent systemic (eg cytotoxic or targeted or other experimental drugs) therapy for BTC.\n13. Prior surgery or locoregional therapy for BTC.\n14. Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last three months, significant arrhythmia).\n15. Presence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent.\n16. Any serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial.\n17. Presence of complete dihydropyrimidine dehydrogenase (DPD) enzyme deficiency with DPYD gene testing mandatory at screening as per national guidelines.\n18. Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.",{"count":237,"type":21},300,[24,147],"PURITY is a multicentre, randomized adaptive phase II\u002FIII trial aimed at comparing the triplet combination of gemcitabine, cisplatin and nabpaclitaxel as neoadjuvant treatment (ARM A) versus standard upfront surgery (ARM B) in terms of 12-month PFS rate (phase II part) and PFS (phase III part) in patients with resectable BTC at high risk for recurrence.",[241,242],"Biliary Tract Cancer","Cholangiocarcinoma",[244,242,245,246],"Biliary Tract Cancers","Neoadjuvant Chemotherapy","Cisplatin Gemcitabine Nabpaclitaxel","2025-02-13",{"date":249,"type":34},"2025-02-17",{"date":251,"type":34},"2023-11-07",{"date":253,"type":21},"2029-01",{"name":40,"class":41},19,{"id":257,"slug":258,"hasResults":11,"nctId":259,"briefTitle":260,"officialTitle":261,"acronym":262,"eligibilityCriteria":263,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":264,"targetDuration":4,"studyType":22,"phases":266,"briefSummary":267,"conditions":268,"keywords":271,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":275,"lastUpdatePostDateStruct":276,"startDateStruct":278,"completionDateStruct":280,"leadSponsor":282,"locationsCount":42},"100535578","phase-2-adjuvant-trastuzumab-deruxtecan-for-her2-positive-gastroesophageal-cancer-with-persistence-of-minimal-residual-disease-100535578","NCT06253650","Adjuvant TRastuzumab Deruxtecan for HER2-positive Gastroesophageal Cancer With Persistence of miNImal Residual Disease","Adjuvant TRastuzumab Deruxtecan Plus Fluoropyrimidine Versus Standard Chemotherapy In HER2-positive Gastric or Gastroesophageal Cancer Patients With Persistence of miNImal Residual Disease in Liquid Biopsy After Pre-operative chemoTherapy and Radical surgerY","TRINITY","Inclusion Criteria of the Interventional TRINITY study:\n\n1. Written informed consent and any locally required authorization (such as the European Union \\[EU\\] Data Privacy Directive) obtained from the patient\u002Flegal representative prior to performing any protocol-related procedures, including screening evaluations.\n2. Compliance with all the study procedures and treatments. Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating Centre.\n3. Age ≥ 18 years old.\n4. Eastern Cooperative Oncology group (ECOG) Performance Status 0-1.\n5. Life expectancy of at least 12 weeks.\n6. Resected gastric or gastroesophageal junction (Siewert I-II-III) cancer\u002Fesophageal adenocarcinoma, after the completion of pre-operative chemotherapy with FLOT, as per standard clinical practice.\n7. Absence of distant metastases as defined by post-operative radiological assessments (contrast-enhanced CT scan of the thorax and abdomen or, in case of contraindications, non-contrast-enhanced chest CT scan and abdomen Magnetic Resonance Imaging)\n8. Presence of locally determined HER2 overexpression\u002Famplification on the post-treatment surgical tissue specimen defined as IHC 3+ or 2+\u002FISH amplified.\n9. Positivity of the post-operative liquid biopsy, performed 2-6 weeks after the radical surgery.\n10. LVEF ≥ 50% within 28 days before randomization\u002Fenrolment.\n11. Adequate bone marrow and organ function within 14 days before randomization\u002Fenrolment as described below:\n\n    1. Neutrophil count ≥ 1.5 x 10\\^3\u002FμL\n    2. Platelet count ≥ 100 x 10\\^6\u002FμL\n    3. Haemoglobin ≥ 9 g\u002FdL\n    4. Total bilirubin lower than 1.5 time the upper-normal limits (ULN) of the Institutional normal values\n    5. AST (SGOT) and\u002For ALT (SGPT) \\\u003C3 x ULN\n    6. serum albumin ≥ 2.5 g\u002FdL\n    7. Creatinine clearance (calculated according to Cockroft and Gault) \\> 60 mL\u002Fmin\n    8. International normalised ratio or Prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤ 1.5 × ULN\n12. Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner. For women of childbearing potential, a negative result for serum pregnancy test (test must have a sensitivity of at least 25 mIU\u002FmL) must be available at the screening visit and urine beta-human chorionic gonadotropin (β-HCG) pregnancy test prior to each administration of IMP. Women of childbearing potential are defined as those who are not surgically sterile (i.e. underwent bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) or post-menopausal. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.\n13. Female patients of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception, from the time of screening and must agree to continue using such precautions for 7 months after the last dose of IMP. Not all methods of contraception are highly effective. Female patients must refrain from breastfeeding while on study and for 7 months after the last dose of IMP. Complete heterosexual abstinence for the duration of the study and drug washout period is an acceptable contraceptive method if it is line with the patient's usual lifestyle (consideration must be made to the duration of the clinical trial); however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable.\n14. Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to 4 months after the final dose of IMP for T-DXd while 6 months for docetaxel and oxaliplatin. Complete heterosexual abstinence for the duration of the study and drug washout period is an acceptable contraceptive method if it is in line with the patient's usual lifestyle (consideration must be made to the duration of the clinical trial); however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable. It is strongly recommended for the female partners of a male patient to also use at least one highly effective method of contraception throughout this period. In addition, male patients should refrain from fathering a child, or freezing or donating sperm from the time of randomisation\u002Fenrolment, throughout the study and for 4 months after the last dose of IMP for T-DXd while 6 months for docetaxel and oxaliplatin. Preservation of sperm should be considered prior to enrollment in this study.\n15. Female subjects must not donate, or retrieve for their own use, ova from the time of randomization\u002Fenrolmentand throughout the study treatment period, and for at least 7 months after the final study drug administration. They should refrain from breastfeeding throughout this time. Preservation of ova may be considered prior to enrollment in this study.\n\nExclusion Criteria of the Interventional TRINITY study:\n\n1. Involvement in the planning and\u002For conduct of the study (applies to both Investigator staff and\u002For staff at the study site)\n2. Participation in another clinical study with an investigational product during the last 12 months\n3. Signs of distant metastases at any site.\n4. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, renal disease, neurological disease or peripheral neuropathy, serious chronic gastrointestinal conditions associated with diarrhea, or substance abuse or any other medical or psychiatric illness\u002Fsocial situations that in the opinion of the investigator would limit compliance with study requirement, interfere with the subject's participation in the clinical study, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent or interfere with the evaluation of the clinical study results.\n5. Patients with a medical history of myocardial infarction (MI) within 6 months before randomization\u002Fenrolment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrollment to rule out MI.\n6. Corrected QT interval (QTcF) prolongation to \\> 470 msec (females) or \\>450 msec (males) based on average of the screening triplicate12-lead ECG.\n7. History of (non-infectious) ILD\u002Fpneumonitis that required steroids, has current ILD\u002Fpneumonitis, or where suspected ILD\u002Fpneumonitis cannot be ruled out by imaging at Screening.\n8. Lung criteria:\n\n   * Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g. pulmonary emboli within three months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.)\n   * Any autoimmune, connective tissue or inflammatory disorders (e.g. Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the eCRF for patients who are included in the study.\n   * Prior pneumonectomy (complete)\n9. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals\n10. Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection not under adequate disease control (that is defined as the presence of all the following conditions: receiving stable regimen of highly active anti-retroviral therapy for at least 4 weeks prior to study enrollment, CD4+ count above 250 cells\u002FμL, undetectable viral load on standard polymerase chain reaction-based tests, absence of any HIV-related opportunistic infections for at least 4 weeks prior to study enrollment and no requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections), or active hepatitis B or C infection (HBsAg, anti-HBs, anti-HBc, anti-HCV). Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients who are anti-HBc positive and HBsAg negative or patients with HBsAg positive have to dose HBV-DNA. If HBV DNA is undetectable (\\\u003C10UL\u002Fml or under the limit of detection per local lab standard) are considered as HBV negative. Subjects should be tested for HIV prior to randomization\u002Fenrollment if required by local regulations or institutional review board (IRB)\u002Fethics committee (EC).\n11. Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of T-DXd. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IMP.\n12. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline. Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to \\>Grade 2 for at least 3 months prior to \\[randomization\u002Fenrollment\u002FCycle 1 Day 1\\] and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy, such as: chemotherapy-induced neuropathy and fatigue.\n13. Known allergy or hypersensitivity to study treatment or any of the study drug excipients.\n14. History of severe hypersensitivity reactions to other monoclonal antibodies.\n15. Pregnant or breastfeeding female patients, or patients who are planning to become pregnant.\n16. Multiple primary malignancies within 3 years, except for\n\n    * adequately resected non-melanoma skin cancer\n    * curatively treated in-situ disease\n    * other solid tumors curatively treated\n17. A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).\n18. LVEF\\\u003C 50% within 28 days before enrolment.\n19. Prior treatment with an anti-HER2 agent.\n20. Absence of locally determined HER2 overexpression\u002Famplification on the surgical specimen defined as IHC 0 or 1+ or 2+\u002FISH not amplified.\n21. Negativity of ctDNA at the post-operative liquid biopsy.\n\n21\\. Known dihydropyrimidine dehydrogenase (DPD) enzyme deficiency based on local laboratory testing before the start of pre-operative FLOT regimen. Confirmation of the assessment of DPD status before the start of pre-operative FLOT in the patient's records should be provided before the enrollment in the interventional study.",{"count":265,"type":21},46,[24],"TRINITY is designed as a multicentre, randomized, open-label, interventional phase II study aimed at investigating the activity, efficacy and safety of trastuzumab-deruxtecan (T-DXd) plus capecitabine\u002F5-fluorouracil as a post-operative treatment in localized\u002Flocally advanced gastric or gastroesophageal junction cancer (GC\u002FGEJC)\u002Fesophageal adenocarcinoma patients with HER2 overexpression\u002Famplification and positive post-operative ctDNA after pre-operative 5-fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) regimen followed by radical surgery.",[269,270],"Gastric Cancer","HER2-positive Gastric Cancer",[272,269,270,273,274],"Trastuzumab-Deruxtecan","Liquid biopsy","Minimal residual disease","2024-06-12",{"date":277,"type":34},"2024-06-13",{"date":279,"type":34},"2024-03-01",{"date":281,"type":21},"2028-03-01",{"name":40,"class":41},{"id":284,"slug":285,"hasResults":11,"nctId":286,"briefTitle":287,"officialTitle":288,"acronym":289,"eligibilityCriteria":290,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":291,"targetDuration":4,"studyType":22,"phases":293,"briefSummary":294,"conditions":295,"keywords":4,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":297,"lastUpdatePostDateStruct":298,"startDateStruct":300,"completionDateStruct":302,"leadSponsor":304,"locationsCount":42},"100414811","phase-2-induction-and-maintenance-treatment-with-parp-inhibitor-and-immunotherapy-in-hpv-negative-hnscc-100414811","NCT04681469","Induction and Maintenance Treatment With PARP Inhibitor and Immunotherapy in HPV-negative HNSCC","Induction and Maintenance Treatment With PARP Inhibitor and Immunotherapy in HPV-negative Head and Neck Squamous Cell Carcinoma (HNSCC)","PRIME","Inclusion Criteria:\n\n1. Patients of both genders, aged ≥18 years;\n2. Signed written informed consent;\n3. Primary histologically proven p16 negative squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx amenable to surgery with curative intent. p16 status will be assessed as surrogate marker for HPV infection only for oropharyngeal cancers. p16 status will be assessed using the CINtec p16 Histology assay (Ventana Medical Systems, Tucson, AZ, USA) with strong and diffuse nuclear and cytoplasmic staining in at least 70% of cells used as the cutpoint for positivity.\n4. Clinical stage III-IV(M0) according to the VIII edition of AJCC staging system; recurrent\u002Fmetastatic HNSCC, or previously treated HNSCC with local or systemic therapies, are not eligible for this study.\n5. Performance status ECOG 0-1;\n6. Availability of fresh tumor tissue via biopsy and provided for study purposes;\n7. Willing to provide blood and saliva samples for study purposes;\n8. Absence of a second malignancy (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, oesophageal, colon, endometrial, cervical\u002Fdysplasia, melanoma, or breast) unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period;\n9. Patient has adequate organ and marrow function (absolute neutrophil count ≥ 1500, hemoglobin ≥ 9.0 gram\u002Fdeciliter (g\u002FdL), platelet count ≥ 100,000, total bilirubin ≤1.5 times institution's upper limit of normal, AST\u002FSGOT and ALT\u002FSPGT ≤ 2.5 times institutional upper limit of normal, albumin ≥ 2.0 g\u002FdL, serum creatinine ≤ 1.5 times institutional upper limit of normal or creatinine clearance ≥ 60 milliliters per minute (mL\u002Fmin) according to Cockroft-Gault formula, or local institutional standard method);\n10. Patient must be able to swallow study drug;\n11. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment;\n12. Female participant has a negative serum pregnancy test within 72 hours prior to taking study treatment if of childbearing potential and agrees to use an adequate method of contraception from screening through 180 days after the last dose of study treatment, or is of nonchildbearing potential. Nonchildbearing potential is defined as follows (by other than medical reasons):\n\n    * ≥45 years of age and has not had menses for \\>1 year\n    * Patients who have been amenorrhoeic for \\\u003C2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation\n    * Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use an adequate barrier method throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. See Section 3.3 for a list of acceptable birth control methods. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.\n13. Participant must agree to not breastfeed during the study or for 90 days after the last dose of study treatment;\n14. Male participant agrees to use an adequate method of contraception (Section 3.3 for a list of acceptable birth control methods) starting with the first dose of study treatment through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient;\n15. Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent.\n\nExclusion Criteria:\n\n1. Patient has recurrent\u002Fmetastatic disease;\n2. Patient with locally advanced disease not amenable of surgery with curative intent;\n3. Patient has received prior local or systemic treatment for HNSCC;\n4. Patient with p16\u002FHPV positive HNSCC;\n5. Patient with sinonasal, nasal cavity or nasopharyngeal cancer;\n6. Patient with SCC on neck disease with unknown primary tumor site;\n7. Patient must not be simultaneously enrolled in an interventional clinical trial;\n8. Patient must not have had major surgery ≤3 weeks prior to initiating protocol therapy and patient must have recovered from any surgical effects;\n9. Participant must not have received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy;\n10. Participant has had radiation therapy encompassing \\>20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy;\n11. Participant must not have a known hypersensitivity to niraparib and TSR-042 components or excipients;\n12. Participant must not have received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy;\n13. Participant must not have received colony stimulating factors (eg, granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy;\n14. Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \\> 4 weeks and was related to the most recent treatment;\n15. Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML);\n16. Participant must not have a serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent;\n17. Participant must not have known, symptomatic brain or leptomeningeal metastases;\n18. Patient experienced ≥ Grade 3 immune-related adverse event with prior immunotherapy, with the exception of non-clinically significant lab abnormalities;\n19. Participant has a diagnosis of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy;\n20. Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer treatment;\n21. Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, oesophageal, colon, endometrial, cervical\u002Fdysplasia, melanoma, or breast) unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period;\n22. Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll;\n23. Subjects with a condition requiring systemic treatment with either corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid \\> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease;\n24. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity;\n25. Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial;\n26. Known active Hepatitis B infection (defined as presence of HBsAg and\u002For HBV DNA), active hepatitis C infection (defined as presence of Hep C RNA) and\u002For known Human Immunodeficiency Virus (HIV). Patients with HIV who have a normal CD4 count (≥ 200) and an undetectable viral load are not excluded;\n27. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 72 hours before treatment start. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 180 days after the last dose of study treatment;\n28. Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results;\n29. History or current evidence of any condition that, in the opinion of the treating investigator, might interfere with the subject's participation for the full duration of the trial.\n30. Participant has received a live vaccine within 14 days of initiating protocol therapy.",{"count":292,"type":21},49,[24],"We propose a window of opportunity trial to evaluate safety and efficacy of a short course of the study combination, composed by an Anti-PD-1 monoclonal antibody (Dostarlimab (TSR-042)) and a PARPi (Niraparib). The study population will be surgically resectable, HPV-negative (defined by p16 negative status) locally advanced HNSCC.\n\nMaintenance treatment will be then delivered, so to better integrate the therapeutic benefits of this drug combination.\n\nResponse to neoadjuvant treatment will be evaluated by the rate of major pathologic response, morphologic, and functional imaging (MRI with functional evaluation -DWI).\n\nWe anticipate that neoadjuvant and maintenance PARPi plus immunotherapy treatment could lead to a reduction of loco-regional recurrence (LRR) and distant metastasis (DM) rates in such a high-risk population.\n\nFurthermore, the window of opportunity portion of this trial will allow in vivo acquisition of valuable knowledge on mechanisms of action and primary resistance to Anti-PD-1 monoclonal antibody and PARPi in HNSCC. In this phase of the study, biological specimens will be collected (pre-treatment tumor biopsy, tissues from the surgical specimen, liquid biopsy, blood and saliva samples) as well as functional imaging (MRI).",[296],"Head and Neck Squamous Cell Carcinoma","2022-08-03",{"date":299,"type":34},"2022-08-04",{"date":301,"type":34},"2021-02-08",{"date":303,"type":21},"2028-06",{"name":40,"class":41},""]