[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"refractory-head-and-neck-squamous-cell-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:refractory-head-and-neck-squamous-cell-carcinoma":37},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,3,0,[8,60,121],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":47,"whyStopped":4,"lastUpdateSubmitDate":48,"lastUpdatePostDateStruct":49,"startDateStruct":52,"completionDateStruct":54,"leadSponsor":56,"locationsCount":59},"100561410","phase-3-testing-the-addition-of-anti-cancer-drug-cetuximab-to-standard-of-care-treatment-pembrolizumab-for-returning-or-spreading-head-and-neck-cancer-after-previous-treatment-100561410",false,"NCT06589804","Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment","Randomized Phase III Trial of Pembrolizumab vs. Pembrolizumab\u002FCetuximab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma With Platinum Refractory Disease","Inclusion Criteria:\n\n* Histologically confirmed diagnosis head and neck squamous cell carcinomas (HNSCC).\n* Previously untreated for recurrent and\u002For metastatic disease incurable by local therapies.\n* Primary tumor location of oral cavity, oropharynx, larynx, or hypopharynx.\n\n  * Note: Other primary tumor sites of HNSCC, including nasopharynx primary tumor are not eligible. Unknown primary tumors may be eligible and can be enrolled at the discretion of the treatment team with approval by the study chair.\n* Measurable disease.\n* Must have platinum-refractory disease defined as disease progression during or ≤ 29 weeks after completion of definitive therapy (chemoradiation therapy) or adjuvant (post-operative) therapy.\n* Patient must have a combined positive score PD-L1 positive (CPS \\>\u002F= 1) tumor.\n* Any radiation therapy must be completed \\>= 10 days prior to registration.\n* Patients should not have received any prior treatment in the recurrent or metastatic setting.\n* Prior therapy with neoadjuvant or induction anti PD-1\u002FPD-L1 monoclonal antibody or cetuximab in the curative setting is allowed if last treatment dose was \\>= 26 weeks prior to registration without evidence of disease progression during that treatment period.\n* Patient has not received a live vaccine within 30 days prior to registration.\n* Patient does not have a history of any contraindication or has a severe hypersensitivity to any component of pembrolizumab or cetuximab (≥ grade 3).\n* Patient has not received chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to registration.\n* Patient with oropharyngeal cancer only must have negative results from testing of human papillomavirus (HPV) status defined as p16 immunohistochemistry (IHC) and\u002For HPV in situ hybridization (ISH).\n\n  * Note: A Clinical Laboratory Improvement Act (CLIA) certified circulating tumor HPV deoxyribonucleic acid (ctHPVDNA) assay can be used if tissue sample is not available.\n* Age ≥ 18 years.\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.\n* Absolute neutrophil count (ANC) ≥ 1,500\u002Fmm\\^3.\n* Platelet count ≥ 100,000\u002Fmm\\^3.\n* Hemoglobin (Hgb) ≥ 9 g\u002FdL (if \\\u003C 9 g\u002FdL, then transfusions are acceptable to increase hemoglobin above 9 g\u002FdL).\n* Creatinine ≤ 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance ≥ 30 mL\u002Fmin using the Cockcroft-Gault formula for participant with creatinine levels \\> 1.5 x institutional ULN.\n* Total bilirubin ≤ 1.5 x ULN OR direct bilirubin \\\u003C ULN for participant with total bilirubin \\> 1.5 x institutional ULN.\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \\[SGPT\\]) ≤ 3.0 x ULN unless liver metastases are present in which case \\\u003C 5.0 x ULN.\n* Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects.\n\n  * Therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 7 days prior to registration is required.\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen should be included.\n* For treated\u002Fstable brain metastases: Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.\n\n  * Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.\n* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial.\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.\n* Patients does not have a history of active myocarditis.\n* Patients does not have a history of any form of pneumonitis or diffuse idiopathic or immune mediated interstitial pulmonary disease.\n* Patient does not have a history of solid organ transplantation.","ALL","18 Years",{"count":19,"type":20},158,"ESTIMATED","INTERVENTIONAL",[23],"PHASE3","This phase III trial compares the effect of adding cetuximab to pembrolizumab versus pembrolizumab alone in treating patients with head and neck squamous cell carcinoma (HNSCC) that has come back after a period of improvement (recurrent) and\u002For that has spread from where it first started (primary site) to other places in the body (metastatic). Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of tumor cells. This may help keep tumor cells from growing. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving cetuximab and pembrolizumab together may be more effective at treating patients with recurrent and\u002For metastatic HNSCC than pembrolizumab alone.",[26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46],"Metastatic Head and Neck Squamous Cell Carcinoma","Metastatic Hypopharyngeal Squamous Cell Carcinoma","Metastatic Laryngeal Squamous Cell Carcinoma","Metastatic Oral Cavity Squamous Cell Carcinoma","Metastatic Oropharyngeal Squamous Cell Carcinoma","Recurrent Head and Neck Squamous Cell Carcinoma","Recurrent Hypopharyngeal Squamous Cell Carcinoma","Recurrent Laryngeal Squamous Cell Carcinoma","Recurrent Neck Squamous Cell Carcinoma of Unknown Primary","Recurrent Oral Cavity Squamous Cell Carcinoma","Recurrent Oropharyngeal Squamous Cell Carcinoma","Refractory Head and Neck Squamous Cell Carcinoma","Refractory Hypopharyngeal Squamous Cell Carcinoma","Refractory Laryngeal Squamous Cell Carcinoma","Refractory Oral Cavity Squamous Cell Carcinoma","Refractory Oropharyngeal Squamous Cell Carcinoma","Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8","Stage IV Hypopharyngeal Carcinoma AJCC v8","Stage IV Laryngeal Cancer AJCC v8","Stage IV Lip and Oral Cavity Cancer AJCC v8","Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8","RECRUITING","2026-06-10",{"date":50,"type":51},"2026-06-11","ACTUAL",{"date":53,"type":51},"2025-03-27",{"date":55,"type":20},"2029-11-30",{"name":57,"class":58},"National Cancer Institute (NCI)","NIH",177,{"id":61,"slug":62,"hasResults":11,"nctId":63,"briefTitle":64,"officialTitle":65,"acronym":4,"eligibilityCriteria":66,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":67,"targetDuration":4,"studyType":21,"phases":69,"briefSummary":71,"conditions":72,"keywords":4,"overallStatus":47,"whyStopped":4,"lastUpdateSubmitDate":110,"lastUpdatePostDateStruct":111,"startDateStruct":113,"completionDateStruct":115,"leadSponsor":117,"locationsCount":120},"100442316","phase-1-iacs-6274-with-or-without-bevacizumab-and-paclitaxel-for-the-treatment-of-advanced-solid-tumors-100442316","NCT05039801","IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors","A Phase 1 Open-Label, Dose-Escalation and Dose-Expansion Study to Investigate the Safety, Pharmacokinetics, and Anti-Tumor Activity of IACS-6274 as Monotherapy and in Combination in Patients With Advanced Solid Tumors","Inclusion Criteria All Parts\n\n1. Provision of written informed consent prior to any study related procedures and compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.\n2. Male or female patients ≥18 years of age at the time of study entry who agree to participate by giving written informed consent prior to participation in any study related activities.\n3. Histologically or cytologically confirmed advanced solid tumors, specifically:\n\n   Dose Escalation for Part A may include:\n\n   Patients with tumors harboring actionable KEAP1\u002FNFE2L2\u002FSTK11\u002FNF1 mutations Patients with low ASNS expression levels (HGSOC or endometrial cancer) Patients who had immunotherapy (IO) melanoma (Minimum treatment duration of prior PD-1 or PD-L1-containing regimen of 12 weeks \\[or equivalent of 2 response evaluations\\]).\n\n   Patients with post-platinum HNSCC Patients with chondrosarcoma Patients with ARID1A mutant clear cell ovarian cancer\n\n   Dose Escalation for Part B may include:\n\n   Confirmed recurrent high-grade non-mucinous ovarian cancer that is platinum-resistant, defined as disease relapse within a platinum-free interval (PFI, or the time elapsed from the last date of platinum dose until PD) of \\\u003C 6 months, and with less than 5 prior therapies\n\n   Dose Expansion for Part B limited to:\n\n   Confirmed recurrent high-grade non-mucinous ovarian cancer with low ASNS expression levels that is platinum-resistant, defined as disease relapse within a PFI of \\\u003C 6 months, and with less than 5 prior therapies.\n\n   Dose Escalation for Part C may include:\n\n   Patients with tumors harboring actionable KEAP1\u002FNFE2L2 mutations Patients with tumors harboring PIK3CA hotspot mutations, activating AKT mutations, and inactivating PTEN mutations (irrespective of KEAP1\u002FNFE2L2 mutations) Patients with low ASNS expression levels (HGSOC)\n\n   Dose Expansion for Part C limited to:\n\n   Patients with NSCLC with actionable KEAP1\u002FNFE2L2 mutations Patients with HGSOClow ASNS expression levels (irrespective of biomarker status for KEAP1\u002FNFE2L2)\n4. Patients must have received at least one line of therapy for advanced stage disease and be refractory or ineligible to available existing therapy(ies) known to provide clinical benefit for their condition.\n5. Prior treatment with chemotherapy, radiotherapy, immunotherapy or any investigational therapies must have been completed at least 3 weeks or at least five half lives, whichever is shorter, before the study drug administration, and all AEs (excluding alopecia and peripheral neuropathy) have either returned to ≤Grade 1 or stabilized. Patients with concurrent use of hormonal therapy for non-cancer related conditions (e.g., hormone replacement therapy) are allowed.\n6. Fresh and\u002For archival tumor tissue from a biopsy obtained between the completion of the most recent line of treatment until study entry must be available for mutation and biomarker analysis. If available, archival tumor tissue from the time of initial diagnosis or the most recent biopsy (archival and\u002For fresh) will be collected. For ovarian cancer patients, a fresh biopsy must be collected in addition to archival tumor tissue. NOTE: No fresh tumor tissue will be required if a previous biopsy detected the selected mutations for each cohort. In all cases, procedures to obtain fresh tumor tissue should not put the patient at undue risk, and should only be performed if the risk is minimal (no greater than 2% risk of serious or severe complications).\n7. Patients must have at least 1 lesion (measurable and\u002For non-measurable) that can be accurately assessed at baseline by CT or MRI and is suitable for repeated assessments.\n8. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.\n9. Adequate organ function as indicated by the following laboratory values:\n\n   Absolute neutrophil count (ANC) ≥1.0×109\u002FL Platelets ≥100×109\u002FL Hemoglobin ≥9.0 g\u002FdL (\\>5.59 mmol\u002FL) Creatinine clearance (CrCl) \\>50 mL\u002Fmin. Actual body weight should be used for calculating creatinine clearance using the Cockroft Gault equation (except for patients with body mass index \\>30 kg\u002Fm2 when the lean body weight should be used, and without the need for chronic dialysis therapy).\n\n   Serum total bilirubin ≤1.5×ULN (with the exception of patients with known thalassemia minor mutations or Gilbert's syndrome: serum total bilirubin must be \\\u003C3×ULN in these patients) Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) ≤2.5×ULN or ≤5×ULN for patients with liver metastases)\n10. Adequate cardiac function with a left ventricular ejection fraction ≥50%\n11. Female patients of non childbearing potential, who are physiologically incapable of becoming pregnant, are eligible to enter and participate in the study if they:\n\n    have had a hysterectomy, OR have had a bilateral oophorectomy, OR have had a bilateral salpingectomy, OR is postmenopausal (total cessation of menses for ≥2 years, or follicle stimulating hormone ≥50 IU\u002FL).\n12. Female patients of childbearing potential, who are not post-menopausal or surgically sterile and intent to be sexually active with a non-sterile male partner, are required to use one form of highly effective contraception combined with a barrier method (male condom, female condom, cervical cap, diaphragm with spermicide, or contraceptive sponge with spermicide) of contraception starting before entering the study and until 4 weeks after the last dose of treatment.\n\n    Highly effective non-hormonal contraceptive methods that are acceptable include:\n\n    Total\u002Ftrue abstinence\\*\\*\\* for the total duration of the study treatment and for at least 1 month after the last dose of study treatment. Periodic abstinence using methods such as calendar ovulation, symptothermal, post ovulation methods, declaration of abstinence solely for the duration of a trial, or withdrawal are not acceptable methods of contraception.\n\n    Having a vasectomized sexual partner, who received post-vasectomy confirmation of azoospermia, combined with a barrier method as described above.\n\n    Bilateral tubal occlusion combined with a barrier method as described above. Intrauterine device with copper banded coils, combined with a barrier method as described above.\n\n    Highly effective hormonal contraceptive methods that are acceptable include:\n\n    Combined oral pill contraception (normal and low-dose oral pills, or progesterone-based oral pills using desogestrel) combined with a barrier method as described above. NOTE: cerazette is currently the only highly efficacious progesterone-based pill available.\n\n    Injection (e.g., medroxyprogesterone) combined with a barrier method as described above.\n\n    Patch (e.g., norelgestromin or ethinyl estradiol transdermal system) combined with a barrier method as described above.\n\n    Implants (etonorgestrel-releasing) combined with a barrier method as described above.\n\n    Intravaginal device (e.g., ethinyl estradiol- or etonogestrel-releasing) combined with a barrier method as described above.\n\n    Intrauterine system (levonorgestrel-releasing) combined with a barrier method as described above.\n\n    In addition to the to use one form of highly effective contraception combined with a barrier method, female patients of childbearing potential must have a negative serum pregnancy test at screening (within 7 days of the start of treatment) and must not be breastfeeding.\n13. Non-sterile men, who are not sexually abstinent and intend to be sexually active with a woman of childbearing potential, must use a condom from the start of the trial and until 16 weeks after the last dose of treatment, or must practice total abstinence\\*\\*\\* for the total duration of the study treatment and at least 3 months after the last dose of study treatment. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Female partners of childbearing potential should consider the use of at least one contraception method describe above. If the female partner is pregnant, male participants should use a condom plus spermicide.\n\n    * Total\u002Ftrue abstinence is defined as a patient who refrains from any form of sexual intercourse, and this is in line with their usual and\u002For preferred lifestyle.\n\nExclusion Criteria All Parts\n\n1. Prior malignancy within the previous 2 years except for locally curable cancers that have been cured, such as basal or squamous cell skin cancer, or carcinoma in situ of the cervix, breast or bladder.\n2. Known primary central malignancy or symptomatic central nervous system metastasis(es).\n\n   Note: Patients with stable, previously treated brain metastases may participate if neurologic symptoms have resolved, patients have been off steroids (at least 7 days for Part A and Part B, and at least 4 weeks for Part C), and there is no evidence of disease progression by imaging for at least 2 weeks before the first dose of study treatment.\n3. Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following cardiac conditions:\n\n   1. Any unstable cardiac arrhythmia within 6 months prior to enrolment\n   2. Prolongation of the Fridericia corrected QT (QTcF) interval defined as \\>450 ms for males and \\>470 ms for females\n   3. History of any of the following cardiovascular conditions within 6 months of enrolment:\n\n      * cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure, as defined by the New York Heart Association.\n4. Major surgical intervention within 28 days before study drug administration, or an anticipated need for major surgery during the study.\n5. Significant acute or chronic infections.\n6. Any psychiatric condition that would prohibit the understanding or rendering of informed consent.\n7. Treatment with strong cytochrome P450 subtype 3A4 (CYP3A4) inducers and inhibitors (including grapefruit juice) within 2 weeks of the first dose of study drug NOTE: patients must have stopped taking St. John's Wort 3 weeks prior to the start of treatment and stopped taking enzalutamide 4 weeks prior to the start of treatment.\n8. Treatment with strong CYP450 subtype 2D6 (CYP2D6) inhibitors or sensitive CYP3A4 substrates within 7 days of the first dose of study drug.\n9. Radiotherapy within 4 weeks prior to the start of study drug. Palliative radiotherapy for symptomatic control is acceptable if completed at least 2 weeks prior to study drug administration and no additional radiotherapy for the same lesion is planned.\n10. Underlying medical conditions (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant and active bleeding diseases), for which in the investigator's opinion will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or AEs.\n11. History of allergic reactions attributed to compounds of similar chemical or biological composition to any of the compounds in the study.\n12. Known history of alcohol or drug abuse.\n13. Legal incapacity or limited legal capacity.\n14. Inability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening or otherwise altering the product formulation. Patients should not have gastrointestinal illnesses (such as refractory nausea and vomiting, chronic gastrointestinal disease or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretionof IACS-6274 and capivasertib, which are oral agents.\n15. Patients unwilling to comply with protocol requirements related to the assigned part.\n16. Any other disease, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.\n\nPart B Specific Exclusion Criteria (B1) Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (that is, three or more features of partially controlled asthma).\n\n(B2) Patient has a known hypersensitivity to paclitaxel or bevacizumab components or excipients.\n\n(B3) Patient has a history of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.\n\n(B4) Patient has proteinuria as demonstrated by urine protein:creatinine ratio ≥1.0 at screening or urine dipstick for proteinuria ≥2 (patients discovered to have ≥2 proteinuria on dipstick at baseline should undergo 24-hour urine collection and must demonstrate \\\u003C2 g of protein in 24 hours to be eligible).\n\n(B5) Patient is at increased bleeding risk due to concurrent conditions (e.g., major injuries or surgery within the past 28 days prior to start of study treatment, history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).\n\n(B6) Patient has clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident \\[CVA\\]) within 6 months of enrollment. (B7) Patient has pre-existing peripheral neuropathy that is Grade ≥2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4 criteria.\n\n(B8) Patient requires paracentesis 2 weeks prior to trial enrolment. Part C Specific Exclusion Criteria (C1) History of another primary malignancy, except for a malignancy treated with curative intent, with no known active disease ≥5 years before the first dose of treatment, with low potential risk for recurrence. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy.\n\n(C2) Patient has a known hypersensitivity to capivasertib components or any excipients of the product.\n\n(C3) Clinically significant abnormalities of glucose metabolism as defined by any of the following: Diagnosis of diabetes mellitus type I or II (irrespective of management), Glycosylated haemoglobin (HbA1c) \\>8% (64 mmol\u002Fmol) (C4) Patients with evidence of severe or uncontrolled systemic liver disease including severe hepatic impairment, or abnormal liver enzymes at screening (AST or ALT \\>2.5 x ULN; total bilirubin \\>1.5 x ULN).\n\n(C5) Patients with elevated alkaline phosphatase (ALP) can be enrolled if the abnormal value is due to the presence of bone metastasis, but liver function is considered adequate according to the principal investigator.\n\n(C6) Patients with persistent toxicities (Grade ≥2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study treatment may be included after consultation with the sponsor and the study physician.\n\n(C7) Patients with spinal cord compression or leptomeningeal disease not requiring steroids for at least 4 weeks prior to start of study intervention.\n\n(C8) Patients with clinically significant cardiovascular disease including, but not limited to, significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident \\[CVA\\]) within 6 months of enrollment. In addition, patients will be excluded based on the study physician's judgment of the following criteria:\n\n* Mean resting corrected QT interval \\>470ms, obtained from triplicate ECGs performed at screening.\n* Medical history significant for arrhythmia that is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation regardless of treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be included based on the study physician's judgment.\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia of Grade ≥1, potential for Torsades de Pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first-degree relative, history of QT prolongation associated with other medications that required discontinuation of the medication.\n* Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association Grade ≥2.\n* Uncontrolled hypotension: SBP \\\u003C90 mmHg and\u002For DBP \\\u003C50 mmHg.\n* Cardiac ejection fraction outside institutional range of normal or \\\u003C50% (whichever is higher) as measured by echocardiogram (or multiple-gated acquisition \\[MUGA\\] scan if an echocardiogram cannot be performed or is inconclusive).\n\n(C9) Patients with active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice) are excluded.\n\n(C10) Patients with active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening are excluded.\n\nHuman immunodeficiency virus (HIV) positive patients with a viral load \\> 400 copies\u002FmL and a CD4+ T-cell count of \\\u003C350 cells\u002FuL or with a history of an acquired immunodeficiency syndrome (AIDS) opportunistic infection within the past 12 months are excluded. Patients with a higher viral load or lower CD4+ count (\\\u003C 350 cells\u002FuL) may be considered for eligibility if the patient has a potentially curable malignancy or for interventions in a later stage of development that have demonstrated prior activity with a given cancer.\n\nHIV-positive patients receiving antiretroviral therapies should be on established ART for at least four weeks before starting treatment to ensure that treatment is tolerated and that toxicities are not confused with investigational drug toxicities. HIV-positive patients receiving antiretroviral therapies that are strong CYP3A4\u002F5 inhibitors\u002F inducers or sensitive substrates of CYP3A4 will be excluded due to the potential for drug-drug interaction with capivasertib.\n\n(C12) Patients who are undergoing any concurrent anticancer treatment or any concomitant medication that may interfere with the study drugs according to local clinical guidelines are excluded.\n\n(C13) Patients who received palliative radiotherapy within 2 weeks prior to the start of study treatment; or radiotherapy to more than 30% of the bone marrow within 4 weeks before the start of study treatment are excluded.",{"count":68,"type":20},54,[70],"PHASE1","To find the highest tolerable dose of IACS-6274 that can be given alone, in combination with bevacizumab and paclitaxel, or in combination with capivasertib to patients who have solid tumors. The safety and tolerability of the study drug(s) will also be studied.",[73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,37,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109],"Advanced Endometrial Carcinoma","Advanced Head and Neck Squamous Cell Carcinoma","Advanced Malignant Solid Neoplasm","Advanced Melanoma","Advanced Ovarian Clear Cell Adenocarcinoma","Chondrosarcoma","Clinical Stage III Cutaneous Melanoma AJCC v8","Clinical Stage IV Cutaneous Melanoma AJCC v8","Pathologic Stage III Cutaneous Melanoma AJCC v8","Pathologic Stage IIIA Cutaneous Melanoma AJCC v8","Pathologic Stage IIIB Cutaneous Melanoma AJCC v8","Pathologic Stage IIIC Cutaneous Melanoma AJCC v8","Pathologic Stage IIID Cutaneous Melanoma AJCC v8","Pathologic Stage IV Cutaneous Melanoma AJCC v8","Recurrent Ovarian High Grade Serous Adenocarcinoma","Refractory Endometrial Carcinoma","Refractory Melanoma","Refractory Ovarian Clear Cell Adenocarcinoma","Refractory Ovarian High Grade Serous Adenocarcinoma","Stage III Ovarian Cancer AJCC v8","Stage III Uterine Corpus Cancer AJCC v8","Stage IIIA Ovarian Cancer AJCC v8","Stage IIIA Uterine Corpus Cancer AJCC v8","Stage IIIA1 Ovarian Cancer AJCC v8","Stage IIIA2 Ovarian Cancer AJCC v8","Stage IIIB Ovarian Cancer AJCC v8","Stage IIIB Uterine Corpus Cancer AJCC v8","Stage IIIC Ovarian Cancer AJCC v8","Stage IIIC Uterine Corpus Cancer AJCC v8","Stage IIIC1 Uterine Corpus Cancer AJCC v8","Stage IIIC2 Uterine Corpus Cancer AJCC v8","Stage IV Ovarian Cancer AJCC v8","Stage IV Uterine Corpus Cancer AJCC v8","Stage IVA Ovarian Cancer AJCC v8","Stage IVA Uterine Corpus Cancer AJCC v8","Stage IVB Ovarian Cancer AJCC v8","Stage IVB Uterine Corpus Cancer AJCC v8","2026-05-29",{"date":112,"type":51},"2026-06-01",{"date":114,"type":51},"2021-09-30",{"date":116,"type":20},"2028-06-30",{"name":118,"class":119},"M.D. Anderson Cancer Center","OTHER",1,{"id":122,"slug":123,"hasResults":11,"nctId":124,"briefTitle":125,"officialTitle":126,"acronym":4,"eligibilityCriteria":127,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":128,"targetDuration":4,"studyType":21,"phases":130,"briefSummary":131,"conditions":132,"keywords":4,"overallStatus":47,"whyStopped":4,"lastUpdateSubmitDate":134,"lastUpdatePostDateStruct":135,"startDateStruct":137,"completionDateStruct":139,"leadSponsor":141,"locationsCount":143},"100532325","phase-1-losartan-pembrolizumab-and-stereotactic-body-radiation-therapy-for-the-treatment-of-patients-with-locally-recurrent-refractory-or-oligometastatic-head-and-neck-squamous-cell-carcinoma-100532325","NCT06211335","Losartan, Pembrolizumab and Stereotactic Body Radiation Therapy for the Treatment of Patients With Locally Recurrent, Refractory or Oligometastatic Head and Neck Squamous Cell Carcinoma","Phase Ib Study of Losartan, Pembrolizumab and Stereotactic Body Radiation Therapy (SBRT) in Patients With Locoregionally Recurrent, Refractory, or Oligometastatic Head and Neck Squamous Cell Carcinoma (HNSCC)","Inclusion Criteria:\n\n* Histologically or cytologically confirmed locoregionally recurrent, refractory, or oligometastatic (at most 4 lesions) squamous cell carcinoma of the head and neck not amenable to curative resection\n* p16 status known for base of tongue, soft palate, and tonsil cancers\n* Tumor amenable to sequential biopsies, and patients willing to undergo sequential tumor biopsies so long as the treating investigator considers them to be clinically safe\n* Prior radiotherapy to the head and neck is allowed. Disease should be limited to up to 4 sites of active disease in the head and neck and\u002For distant metastatic sites if deemed safely treatable by physician, or adjacent sites treatable in single contiguous target volume with a recommended maximum total tumor dimension (GTV) of \\\u003C 7.5 cm. However, larger volumes may be allowed after discussion with primary investigator (PI) and careful review of radiation dose constraints\n* Prior systemic therapy is allowed. Patients with locoregional relapses where radiation alone would be indicated are allowed to enroll without prior systemic therapy\n* Presence of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) with a target on a computed tomography (CT) scan or magnetic resonance imaging (MRI) available for review\n* Combined positive score (CPS) \\> 1%\n* Age ≥ 18 years at time of consent\n* Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1\n* Leukocytes ≥ 3 × 10\\^9\u002FL\n* Absolute neutrophil count ≥ 1.5 × 10\\^9\u002FL\n* Platelets ≥ 100 × 10\\^9\u002FL\n* Hemoglobin (Hgb) ≥ 9 g\u002FdL, transfusions may be used to raise Hgb to ≥ 9 g\u002FdL (no washout required)\n* Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)\n* Aspartate transaminase (AST) \u002F alanine transaminase (ALT) ≤ 2.5 × institutional ULN\n* Creatinine within normal institutional limits OR creatinine clearance ≥ 30 mL\u002Fmin\u002F1.73 m\\^2 for patients with creatinine above institutional ULN\n* The effects of losartan on the developing human fetus are unknown. For this reason, individuals of childbearing potential and male participants with partners of childbearing potential, must agree to use methods of contraception for the duration of study participation (including dosing interruptions) and for up to 3 months after last study treatment; or be surgically sterilized\n* Ability to understand and willingness to sign and date the informed consent form\n* Stated ability and willingness to adhere to the study visit schedule and protocol requirements\n\nExclusion Criteria:\n\n* Nasopharyngeal carcinoma, salivary gland carcinoma or primary skin squamous cell carcinoma (SCC)\n* Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody\n* Chemotherapy or other anti-cancer therapy within 3 weeks prior to study day 1\n* Hypersensitivity to losartan or any component of the formulation\n* Radiation therapy within 6 months prior to study day 1\n* Patients with disease surrounding \\> 50% of the carotid\n* Participant who has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade ≤ 1 from an adverse event (AE) due to previous cancer therapeutics (i.e., chemotherapy, radiation therapy, biologic therapy, and\u002For experimental therapy) with the exception of alopecia\n* Major surgery as assessed by the investigator (with the exception of diagnostic biopsy) within ≤ 28 days prior to study day 1 (patients must have completely recovered from any previous surgery prior to study day 1)\n* Clinically significant bleeding ≤ 4 weeks prior to study day 1\n* Requirement for parenteral antibiotics, or any active infection requiring parenteral antibiotic therapy within 4 weeks prior to study day 1\n* Clinically significant or uncontrolled diabetes mellitus (hemoglobin A1C ≤ 8.5%). Patients with diabetes mellitus treated with aliskiren ≤ 7 days prior to study day 1 are excluded\n* Active autoimmune disorders that have required systemic treatment with disease modifying agents, corticosteroids, or immunosuppressive drugs in the past 2 years are excluded. Patients with autoimmune disorder or well-managed or inactive autoimmune disorders, such as Hashimoto's thyroiditis, may be allowed at the discretion of the PI\n* Current use of systemic corticosteroids equivalent to \\>10 mg of prednisone per day\n* Current use of angiotensin receptor blockers (ARBs) or angiotensin converting enzyme (ACE) inhibitors for management of hypertension\n* Clinically significant cardiovascular, pulmonary, endocrine, neurologic, gastrointestinal or genitourinary disease unrelated to underlying solid tumor that in the judgment of the investigator should preclude treatment with losartan\n* Any other active malignancy except for low-risk prostate cancer previously treated or under active surveillance, uncomplicated and cured basal cell carcinoma, or squamous cell carcinoma of the skin within 5 years of study entry\n* Known history of positive hepatitis C (HCV) antibody, hepatitis B (HBV) surface antigen (HbsAg and HBV core Ab positive), or human immunodeficiency virus (HIV) antibody results. Patients with positive antibody tests are eligible with negative viral loads\n* Administration of live, attenuated vaccine ≤ 28 days prior to study day 1. Administration of inactivated flu vaccines is allowed\n* Any prior treatment with losartan or other specific TGF-β-directed therapy\n* Treatment with another investigational drug or device, or approved therapy for investigational use ≤ 28 days prior to study day 1, or if the half-life of the previous product is known, within 5 times the half-life prior to study day 1, whichever may be longer\n* Pregnant or breast feeding\n* Any condition that in the opinion of the investigator would interfere with the participant's safety, compliance while on trial, or understanding or rendering of informed consent",{"count":129,"type":20},24,[70],"This phase Ib trial tests the safety, side effects and how well losartan, pembrolizumab and stereotactic body radiation therapy (SBRT) for the treatment of patients with head and neck squamous cell carcinoma that has come back to nearby tissue or lymph node after a period of improvement (locally recurrent), that has not responded to previous treatment (refractory) or that has spread from where it first started to multiple other placed in the body (oligometastatic). Losartan is a drug used to treat high blood pressure that may enhance the effects of other cancer treatments such as immunotherapy and radiation. Immunotherapy with pembrolizumab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Giving losartan, pembrolizumab and SBRT may work better in treating patients with locally recurrent, refractory or oligometastatic head and neck squamous cell carcinoma.",[133,26,37],"Locally Recurrent Head and Neck Squamous Cell Carcinoma","2026-03-10",{"date":136,"type":51},"2026-03-12",{"date":138,"type":51},"2023-12-07",{"date":140,"type":20},"2027-06",{"name":142,"class":119},"University of California, Davis",2]