[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"diffuse-hemispheric-glioma-h3-g34-mutant\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:diffuse-hemispheric-glioma-h3-g34-mutant":69},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,45,79,106],{"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":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":34,"startDateStruct":37,"completionDateStruct":39,"leadSponsor":41,"locationsCount":44},"100610088","phase-1-a-study-of-177lu-psma-617-in-people-with-gliomas-100610088",false,"NCT07223034","A Study of 177Lu-PSMA-617 in People With Gliomas","LU-TARGET: A Phase 1 Study of Lutetium-177-PSMA-617 Adjuvant Radiotherapy for IDH Wild Type Gliomas Expressing PSMA Following Standard Treatment","Inclusion Criteria:\n\n* Confirmed histologic diagnosis of a WHO grade 2-4 glioma that is IDH1 R132H-wildtype, including the following:\n\n  * Diffuse astrocytoma, IDH-wildtype (grade 2-4)\n  * Glioblastoma, IDH-wildtype\n  * Diffuse midline glioma, H3 K27-altered\n  * Diffuse hemispheric glioma, H3 G34-mutant\n  * Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype PSMA positive pathological stain (by immunohistochemistry) of baseline (pre-radiotherapy) resection or biopsy sample\n* Completion of standard of care therapy including surgery (for resectable tumors) and adjuvant EBRT for glioma\n* Patients must be on a dose of 4 mg or less of dexamethasone (or dexamethasone equivalent steroid) for 5 days prior to first planned dose of radiopharmaceutical\n* Age ≥ 18\n* ECOG ≤ 2\n* Serum creatinine level \\\u003C 1.5 x ULN or EGFR \\> 60 mL\u002Fmin\n* Liver laboratory values: ALT and AST ≤ 2.5 x ULN; Albumin \\> 2 g\u002F dL; Bilirubin \\\u003C 3 X ULN\n* Normal organ and marrow function as defined as the following\n\n  * Total white blood count \\> 3.0 K\u002FmcL\n  * ANC ≥ 1.5 K\u002FmcL\n  * Platelets ≥ 100 K\u002FmcL\n  * Hemoglobin ≥ 9 g\u002FdL\n* Adequate contraception prior to registration (see section 9.0)\n* Ability to understand, and willingness to sign the informed consent.\n\nExclusion Criteria:\n\n* Patient known to harbor any other non-canonical IDH mutations (i.e., non-R132H)\n* Target lesion within 5 mm of either the brainstem, optic chiasm or optic nerves Receipt of bevacizumab as part of the initial treatment for glioma\n* Life expectancy less than 12 weeks\n* Nonhealing wound, ulcer or bone fracture\n* History of severe brain injury\n* Patient not eligible for sequential MRI evaluations\n* Patients with prior RT to \\> 25% of the skeleton or prior exposure to prior Radium223, Strontium89 or Samarium153 containing compounds\n* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen\n* Unable to tolerate the PSMA PET\u002FMR or PSMA PET\u002FCT\n* History of viral hepatitis or chronic liver disease with active symptoms\n* History of pituitary or adrenal dysfunction\n* Previously diagnosed active infection (e.g., human immunodeficiency virus \\[HIV\\] or viral hepatitis)\n* Any condition that in the opinion of the investigator, would preclude participation in this study\n* Receipt of any other investigational agents or participation in a concurrent treatment protocol\n* Known allergies, hypersensitivities, or intolerance to 68Ga-PSMA-11\u002F177Lu-PSMA-617 or its inactive compounding components\n* Current or planned pregnancy\n* Refusal to comply with detailed contraception requirements","ALL","18 Years",{"count":19,"type":20},20,"ESTIMATED","INTERVENTIONAL",[23],"PHASE1","The researchers are doing this study to find out whether the radiopharmaceutical therapy (RPT) 177Lu-PSMA-617 is a safe treatment for people with IDH wild type glioma.",[26,27,28,29,30,31],"Glioma","Diffuse Astrocytoma, IDH-Wildtype (Grade 2-4)","Glioblastoma, IDH-wildtype","Diffuse Midline Glioma, H3 K27-Altered","Diffuse Hemispheric Glioma, H3 G34-mutant","Diffuse Pediatric-type High-grade Glioma, H3-wildtype and IDH-wildtype","RECRUITING","2026-06-02",{"date":35,"type":36},"2026-06-04","ACTUAL",{"date":38,"type":36},"2025-10-27",{"date":40,"type":20},"2027-10",{"name":42,"class":43},"Memorial Sloan Kettering Cancer Center","OTHER",7,{"id":46,"slug":47,"hasResults":11,"nctId":48,"briefTitle":49,"officialTitle":50,"acronym":4,"eligibilityCriteria":51,"healthyVolunteers":11,"sex":16,"minAge":52,"maxAge":53,"enrollmentInfo":54,"targetDuration":4,"studyType":21,"phases":56,"briefSummary":58,"conditions":59,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":70,"lastUpdatePostDateStruct":71,"startDateStruct":73,"completionDateStruct":75,"leadSponsor":77,"locationsCount":19},"100504051","phase-2-study-of-ribociclib-and-everolimus-in-hgg-and-dipg-or-ribociclib-and-temozolomide-in-dhg-h3g34-mutant-100504051","NCT05843253","Study of Ribociclib and Everolimus in HGG and DIPG or Ribociclib and Temozolomide in DHG, H3G34-mutant","Phase 2 Study of Ribociclib-Containing Post-Radiotherapy Combinations in Pediatric and Young Adult Patients Newly Diagnosed With High-Grade Glioma, Including Diffuse Intrinsic Pontine Glioma: Ribociclib and Everolimus for HGG\u002FDIPG Which Harbor Alterations of the Cell Cycle and\u002For PI3K\u002FmTOR Pathways AND Ribociclib and Temozolomide for DHG, H3G34-mutant","TarGeT-A study strata definitions Part1: Initial Feasibility Study for the combination of ribociclib PfOS formulation with everolimus: Enrollment on this cohort will be limited to patients aged \\\u003C21 years with primary intracranial localized HGG and DIPG\n\nPart 2\n\n* Stratum A: Patients with localized, intracranial, non-pontine, and non-thalamic HGG (who do not meet criteria for strata C-D)\n* Stratum B: Patients with DIPG\n* Stratum C: Patients with primary thalamic, spinal cord, and\u002For secondary\u002Fradiation-related HGG.\n* Stratum D: Patients with metastatic\u002Fdisseminated HGG, multifocal HGG, and\u002For gliomatosis cerebri who received CSI.\n\nStratum E\n\n* Stratum E: Patients with localized DHG, H3G34-mutant.\n\nInclusion Criteria:\n\n1. Inclusion criteria already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on:\n\n   1.1) Age: patients must be ≥12 months and ≤39 years of age at the time of enrollment on TarGeT-SCR. For the Part 1 Initial Feasibility Cohort (receiving ribociclib and everolimus) only: patients must be \\\u003C21 years of age at the time of enrollment on this protocol.\n\n   1.2) Diagnosis: patients with newly-diagnosed HGG, including DIPG are eligible. All patients must have histologic confirmation tumor tissue from diagnostic biopsy or resection, without exceptions. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR:\n   * For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons, with histopathology, consistent with diffuse WHO grade 2-4 glioma\n   * All other HGGs must be WHO grade 3 or 4.\n\n   1.3) Disease status: There are no disease status requirements for enrollment\n   * Patients without measurable disease are eligible.\n   * Patients with metastatic or multifocal disease or gliomatosis cerebri who received upfront CSI are eligible\n   * Patients with a primary spinal HGG are eligible\n   * Patients with secondary, radiation-related HGG are eligible.\n2. Inclusion criteria for assignment to TarGeT-A, for all strata:\n\n2.1) Presence of at least one relevant actionable somatic alteration, detailed here:\n\n* Pathogenic alterations presumed to cause activation of cell cycle:\n* Amplification of CDK4 or CDK6\n* Deletion of CDKN2A, CDKN2B, or CDKN2C\n* Amplification of CCND1 or CCND2\n* Pathogenic alterations presumed to cause activation of the PI3K\u002FmTOR pathway:\n* Deletion or mutation of PTEN\n* Mutation or amplification of PIK3CA\n* Mutation of PIK3R1\n* Deletion or mutation of TSC1 or TSC2\n* Patients with evidence of homozygous (biallelic) RB1 loss by sequencing are excluded from TarGeT-A\n* Patients whose tumors harbor other alterations suspected to activate the cell cycle and\u002For PI3K\u002FmTOR pathway could potentially also be eligible, but only following consensus recommendation by the international multidisciplinary molecular screening committee.\n* For Stratum E: H3G34 (R\u002FV) mutation\n\n2.2) Performance Level: Karnofsky ≥ 50% for patients \\> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of ag. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n\n2.3) Prior Therapy for HGG:\n\n* Surgery, RT, dexamethasone are permissible. Temozolomide administered concurrently with RT is permissible. Avastin\u002Fbevacizumab use is permitted given the last dose was administered \\> 21 days prior to enrollment. No other prior anticancer therapy for HGG will be allowed.\n* Patients must have received photon or proton RT.\n* Patients must have started RT \\\u003C 42 calendar days from initial diagnosis defined as the date of diagnostic biopsy or resection. If a patient underwent 2 upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery.\n* RT delivered via photon or proton beam, must have been administered at a standard dose including (54 Gy in 30 fractions for DIPG, 54-59.4 Gy in 30-33 fractions), 45 Gy-54 Gy for primary spinal disease, and\u002For 36 Gy-39.6 Gy craniospinal for patients with spinal or leptomeningeal metastatic disease with supplemental boost to 45-54 Gy for metastasis within the thecal sac and 54 Gy-60 Gy for intracranial metastasis. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Sponsor-Investigator to confirm eligibility prior to study enrollment.\n* Patients must enroll and start treatment No later than 35 calendar days post-completion of RT. The earliest patients can begin protocol treatment is 28 calendar days post-completion of RT.\n\n2.4) Organ Function Requirements\n\n2.4.1) Adequate Bone Marrow Function Defined as:\n\n* Peripheral absolute neutrophil count (ANC) ≥ 1000\u002Fmm3\n* Platelet count ≥ 100,000\u002Fmm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)\n* Hemoglobin \\>8 g\u002FdL (may be transfused)\n\n2.4.2) Adequate Renal Function Defined as:\n\n* Creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m2 OR\n* Maximum serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age\u002Fgender as follows: 1 to \\\u003C 2 years=0.6 mg\u002FdL for males and females; 2 to \\\u003C 6 years=0.8 mg\u002FdL for males and females; 6 to \\\u003C 10 years= 1.0 mg\u002FdL for males and females; 10 to \\\u003C 13 years=1.2 mg\u002FdL for males and females. 13 to \\\u003C 16 years=1.5 mg\u002FdL for males and 1.4 mg\u002FdL for females.\n\n2.4.3) Adequate Liver Function Defined as:\n\n* Total bilirubin must be ≤ 1.5 times institutional upper limit of normal for age\n* AST(SGOT)\u002FALT(SGPT) ≤ 3 times institutional upper limit of normal\n* Serum albumin ≥ 2g\u002FdL\n\n2.4.4) Adequate Cardiac Function Defined as:\n\n* Ejection fraction of ≥ 50% by echocardiogram\n* QTc ≤ 450 msec (by Bazett formula)\n\n2.4.5) Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not strong inducers or inhibitors of CYP3A4\u002F5.\n\n2.4.6) Adequate Pulmonary Function Defined as: No evidence of dyspnea at rest, and a pulse oximetry \\>94% on room air if there is clinical indication for determination.\n\n2.5) Ability to take medications by mouth: For ribociclib and everolimus strata, patients must be able to take study medications by mouth as administration via NG\u002FNJ\u002FG tube is not allowed.\n\n2.6) Informed Consent: All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines\n\n2.7) Contraception: Male and female patients of childbearing potential must be willing to use a highly effective contraception method.\n\nExclusion Criteria\n\n1. Pregnant or Breast-Feeding Pregnant or breast-feeding women will not be entered on this study due to known potential risks of fetal and teratogenic adverse events as seen in animal\u002Fhuman studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use at least one highly effective method of contraception while being treated on this study and for 3 months after completing therapy. A woman is considered of childbearing potential if she is fertile, following menarche and until becoming post-menopausal unless permanently sterile. 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. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. Male participants should refrain from sperm donation throughout the duration of treatment and for 3 months after completion of therapy\n\n   A highly effective contraception method is defined as one that results in a low failure rate (\\\u003C1% per year) when used consistently and correctly. The following are considered highly effective contraception methods:\n   * Combined estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation.\n   * Progesterone-only hormonal contraception associated with inhibition of ovulation.\n   * Intra Uterine Device (IUD)\n   * Intra Uterine hormone releasing system\n   * Bilateral tubal occlusion\n   * Vasectomized partner\n   * Sexual abstinence (avoiding having heterosexual intercourse) The following contraceptive measures are NOT considered effective\n   * Progesterone-only hormonal contraception (birth control pill) that that does NOT stop ovulation\n   * Male or female condom with or without spermicide\n   * Cap, diaphragm or sponge with spermicide\n2. Concomitant Medications\n\n   * Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported.\n   * Patients who are currently receiving another investigational drug are not eligible.\n   * Patients who are currently receiving other anti-cancer agents are not eligible, with the exception of temozolomide given concurrently with RT only.\n   * Patients who are receiving enzyme inducing anticonvulsants that are strong inducers or inhibitors of CYP3A4\u002F5 are not eligible.\n   * Patients who are receiving strong inducers or inhibitors of CYP3A4\u002F5 are not eligible and should be avoided from 14 days prior to enrollment to the end of the study.\n   * Patients who are receiving medications known to prolong QTc interval are not eligible.\n   * Patients who are receiving therapeutic anticoagulation with warfarin or other coumadin-derived anticoagulants are not eligible. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed as long as the patient has adequate coagulation defined as aPTT \\\u003C 1.5Xs ULN and INR \\\u003C 1.5.\n3. Patients who have an uncontrolled infection are not eligible.\n4. Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.\n5. Patients with known clinically significant active malabsorption syndrome or other condition that could affect absorption are not eligible.\n6. Patients with prior or ongoing clinically significant medical or psychiatric condition that, in the investigator's opinion, could affect the safety of the subject, or could impair the assessment of study results are not eligible.","12 Months","39 Years",{"count":55,"type":20},120,[57],"PHASE2","The goal of this study is to determine the efficacy of the 1) ribociclib and everolimus to treat pediatric and young adult patients newly diagnosed with a high-grade glioma (HGG), including DIPG, that have genetic changes in pathways (cell cycle, PI3K\u002FmTOR) that these drugs target or 2) ribociclib and temozolomide to treat pediatric and young adult patients newly diagnosed with diffuse hemispheric glioma (DHG), H3G34-mutant.\n\nThe main question the study aims to answer is whether the combinations of ribociclib and everolimus or ribociclib and temozolomide can prolong the life of patients diagnosed with HGG\u002FDIPG or DHG H3G34-mutant.",[60,61,62,63,64,65,66,67,68,69],"High Grade Glioma","Diffuse Intrinsic Pontine Glioma","Anaplastic Astrocytoma","Glioblastoma","Glioblastoma Multiforme","Diffuse Midline Glioma, H3 K27M-Mutant","Metastatic Brain Tumor","WHO Grade III Glioma","WHO Grade IV Glioma","Diffuse Hemispheric Glioma, H3 G34-Mutant","2026-05-27",{"date":72,"type":36},"2026-05-29",{"date":74,"type":36},"2024-08-22",{"date":76,"type":20},"2034-08-28",{"name":78,"class":43},"Nationwide Children's Hospital",{"id":80,"slug":81,"hasResults":11,"nctId":82,"briefTitle":83,"officialTitle":84,"acronym":85,"eligibilityCriteria":86,"healthyVolunteers":11,"sex":16,"minAge":87,"maxAge":4,"enrollmentInfo":88,"targetDuration":4,"studyType":21,"phases":90,"briefSummary":91,"conditions":92,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":96,"lastUpdatePostDateStruct":97,"startDateStruct":99,"completionDateStruct":101,"leadSponsor":103,"locationsCount":105},"100564521","phase-1-5g-ruby-avutometinib-and-defactinib-in-malignant-brain-tumours-100564521","NCT06630260","5G-RUBY: Avutometinib and Defactinib in Malignant Brain Tumours","A Phase 1\u002F2 Trial of the Doublet Combination of Avutometinib and Defactinib and as a Triplet in Combination With Temozolomide in Patients With High Grade Malignant Brain Tumours Within the 5G Platform","5G-RUBY","Inclusion Criteria for Phase 1b:\n\n1. Patients with histologically confirmed advanced WHO Stage IV glioblastoma (per fourth edition 2016). Per the new 2021 fifth edition of WHO Classification of Tumours of the Central Nervous System, this will include:\n\n   * Glioblastoma, IDH-wildtype Grade 4\n   * Astrocytoma, IDH-mutant, Grade 4 (lower Grade 2\u002F3 are not included)\n   * Diffuse hemispheric glioma, H3 G34 mutant Grade 4\n\n   Patients with any other CNS tumours will only be eligible for defined Phase 2 biomarker arms once a Phase 1b GO decision has been met. Specific eligibility criteria for these tumours will be defined following an amendment.\n2. Patients for Phase 1 will need to have consented to the Minderoo Precision Brain Tumour Programme and have available whole genome, and transcriptome data available.\n3. Patients for the relapsed cohorts will be eligible at first relapse following completion of optimal surgery, and Stupp based adjuvant chemo-radiotherapy (or equivalent). They will need to have measurable disease per RANO or evaluable disease.\n4. Patients for the front line minimal residual disease (mrd) cohort will be eligible following completion of optimal surgery and Stupp based adjuvant chemoradiotherapy as long as they meet all other inclusion\u002Fexclusion criteria.\n5. 16 years or over\n6. Life expectancy of at least 12 weeks.\n7. World Health Organisation (WHO) performance status of 0-1\n8. Neurologically stable (e.g., without a progression of neurological symptoms or requiring escalating doses of systemic steroid therapy within the last week)\n9. Written (signed or dated) informed consent and be capable of co-operating with treatment and follow up\n10. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week prior to the first dose of either IMP\n\n    Haemoglobin (Hb): ≥ 9.0 g\u002FdL; Absolute neutrophil count: ≥1.5 x 10\\^9\u002FL; Platelet count: ≥100 x 10\\^9\u002FL; Coagulation: INR \\\u003C1.5 and APTT \\\u003C1.5x if not anticoagulated, INR stable \\> 7 days within intended therapeutic range if anticoagulated; Bilirubin: Within institution normal ranges; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): \\\u003C3 x ULN; Albumin: ≥ 28 g\u002FdL; Creatinine: \\\u003C1.5 x ULN; Sodium: ≥130 mmol\u002FL; Potassium, Calcium, Magnesium, phosphate: Within institution normal ranges (replacement is permitted); Urinary protein: \\\u003C 1+ on dipstick.\n11. Female patients with reproductive potential must have a negative serum pregnancy test within 14 days prior to start of trial.\n12. Men and women of childbearing potential must agree to comply with the use of a highly effective method of contraception to avoid impregnating a partner or becoming pregnant, respectively, during the study, and for at least 150 days after the last dose of either investigational drug.\n\nExclusion Criteria for Phase 1b:\n\n1. Receipt of treatment before the first dose of study drug (Cycle 1 Day 1) within an interval shorter than the following, as applicable:\n\n   * Cytotoxic chemotherapy during the prior 2 weeks or 6 weeks for nitrosoureas\n   * Bevacizumab during the prior 6 weeks\n   * Five half-lives of any small molecule investigational or licensed medicinal product.\n2. Prior immune checkpoint inhibitor therapy or vaccine therapy is not permitted. Prior use of any other immune-modulatory investigational agent must be discussed with sponsor team and CI. Prior use of BRAF or MEK inhibitors is not permitted.\n3. Ongoing Grade 2 or greater toxicities from pre-existing conditions or from previous treatments.\n4. Patients with carcinomatous meningitis, leptomeningeal spread of tumour, spread of tumour to the brain stem or spinal cord.\n5. Has evidence of recent intratumoural or peritumoural haemorrhage on baseline MRI. Patients with radiological findings that are stable on at least 2 consecutive MRI scans at least 3 weeks apart will be eligible.\n6. History of clinically relevant bleeding disorders, including significant GI bleeding within last 6 months.\n7. History of arterial thromboembolism.\n8. Recent (within 3 months) deep vein thrombosis or pulmonary embolism or another significant thromboembolism. Venous port of catheter thrombosis or superficial thrombosis are not considered significant. Patients with prior thrombosis (\\> 3 months ago) on stable anticoagulation are permitted to be enrolled. Patients on Warfarin will need to be converted onto low-molecular weight-based heparin therapy.\n9. History of clinically significant cardiac disorders:\n\n   * Myocardial infarction, or New York Heart Association Class II to IV congestive heart failure, within 6 months of the first dose of study drug\n   * Concurrent and clinically significant abnormalities on ECG at Screening, including a corrected QT interval (QTcF \\>460ms).\n10. History of malabsorption syndrome or other conditions that may interfere with enteral absorption. Patients with a history of or active inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis). Patients with acute or chronic pancreatitis. History of gastrointestinal perforation or fistulae. Patients with known Gilbert's syndrome will be excluded from this study.\n11. Concurrent ocular disorders:\n\n    1. Patients with history of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including uncontrolled hypertension, uncontrolled diabetes\n    2. Patient with history of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO, intraocular pressure \\> 21 mm Hg as measured by tonometry, or other significant ocular pathology, such as anatomical abnormalities that increase the risk for RVO.\n    3. Patients with a history of corneal erosion (instability of corneal epithelium), corneal degeneration, active or recurrent keratitis, and other forms of serious ocular surface inflammatory conditions.\n12. Has urine protein \\> 1g\u002F24 hours. Participants with \\>1+ on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria.\n13. Has significant lung disease including pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, active tuberculosis, or history of opportunistic infections (including PCP or CMV pneumonia).\n14. Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).\n15. Steroid requirement for neurological symptom control of \\> 3mg Dexamethasone per day (patients will allowed to enrol if they have been on a stable dose of steroids of equivalent or less than 3mg Dexamethasone for at least 5 days prior to Day 1 of Cycle 1).\n16. Has received a live vaccine within 30 days of planned start of study therapy. Note: inactive vaccines including COVID vaccines are allowed prior to 1 week of Day 1 of Cycle 1).\n17. Current active concurrent malignancy. Cancer survivors who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease recurrence for three years or more and are deemed at negligible risk of recurrence will be eligible.\n18. Is a participant or plans to participate on another interventional clinical trial while taking part in this Phase 1 study. Participation in an observational trial would be acceptable.\n19. Exposure to medications (with or without prescriptions), supplements, herbal remedies, or foods with potential for drug-drug interactions with study interventions within 14 days prior to the first dose of study intervention and during the course of therapy, including:\n\n    1. Strong CYP3A4 inhibitors or inducers, due to potential drug-drug interactions with both avutometinib and defactinib.\n    2. Strong CYP2C9 inhibitors or inducers, due to potential drug-drug interactions with defactinib. Not applicable if and when patients randomized to avutometinib monotherapy.\n    3. Strong P-glycoprotein (P-gp) inhibitors or inducers, due to potential drug-drug interactions with both avutometinib and defactinib.\n    4. Strong breast cancer resistance protein (BCRP) inhibitors or inducers, due to potential drug-drug interactions with avutometinib.\n20. Major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or palliative radiotherapy within 1 week of the first dose of defactinib.\n21. Any other condition which in the investigator's opinion would not make the patient a good candidate for the clinical trial.","16 Years",{"count":89,"type":20},182,[23,57],"The purpose of this clinical trial is to evaluate the safety and tolerability of avutometinib and defactinib and to determine the preliminary antitumour activity of avutometinib and defactinib administered at the recommended Phase 2 dose (RP2D). In the Phase 1b of this study parallel biomarker defined arms will be opened, initially in the relapsed GMB setting, enrolling 12 patients onto each arm. These patients will be treated with avutometinib and defactinib double therapy. Avutometinib will be administered orally at 3.2mg twice a week (e.g., on Monday \u002F Thursday or Tuesday \u002F Friday) with or without a meal. The total weekly dose of avutometinib is 6.4mg. Defactinib will be administered orally, at 200mg, twice a day within 30 min after a meal. The total daily dose of defactinib is 400mg.\n\nOnce a treatment in any biomarker arm has met the \"GO\" decision (≥3 successes\u002F12 patients) for relapsed GBM in Phase 1b, that arm can progress to Phase 2. The primary objective of Phase 2 is to determine the antitumour activity of investigational agents administered at the RP2D in patients with molecularly defined malignant brain tumours.",[93,94,69,95],"Glioblastoma Multiforme (GBM)","Glioblastoma Multiform (Grade IV Astrocytoma)","Malignant Primary Gliomas","2026-01-19",{"date":98,"type":36},"2026-01-21",{"date":100,"type":36},"2024-11-15",{"date":102,"type":20},"2030-09-30",{"name":104,"class":43},"Institute of Cancer Research, United Kingdom",3,{"id":107,"slug":108,"hasResults":11,"nctId":109,"briefTitle":110,"officialTitle":111,"acronym":112,"eligibilityCriteria":113,"healthyVolunteers":11,"sex":16,"minAge":87,"maxAge":4,"enrollmentInfo":114,"targetDuration":4,"studyType":21,"phases":116,"briefSummary":117,"conditions":118,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":119,"lastUpdatePostDateStruct":120,"startDateStruct":122,"completionDateStruct":124,"leadSponsor":126,"locationsCount":127},"100564673","phase-1-5g-emerald-amivantamab-in-malignant-brain-tumours-100564673","NCT06632236","5G-EMERALD: Amivantamab in Malignant Brain Tumours","5G-EMERALD: A Phase 1 Trial of Amivantamab in High Grade Malignant Brain Tumours Within the 5G Platform","5G-EMERALD","Inclusion Criteria for Phase 1b:\n\n1. Patients with histologically confirmed advanced WHO Stage IV glioblastoma (per fourth edition 2016). Per the new 2021 fifth edition of WHO Classification of Tumours of the Central Nervous System, this will include:\n\n   * Glioblastoma, IDH-wildtype Grade 4\n   * Astrocytoma, IDH-mutant, Grade 4 (lower Grade 2\u002F3 are not included)\n   * Diffuse hemispheric glioma, H3 G34 mutant Grade 4\n2. Patients for Phase 1 will need to have consented to the Minderoo Precision Brain Tumour Programme and have available whole genome, and transcriptome data available.\n3. Patients for the relapsed cohorts will be eligible at first relapse following completion of optimal surgery, and Stupp based adjuvant chemo-radiotherapy (or equivalent). They will need to have measurable disease per Response Assessment in Neuro-Oncology (RANO) or evaluable disease.\n4. Patients for the front line minimal residual disease (MRD) cohort will be eligible following completion of optimal surgery and Stupp based adjuvant chemoradiotherapy as long as they meet all other inclusion\u002Fexclusion criteria.\n5. 16 years or over.\n6. Life expectancy of at least 12 weeks.\n7. World Health Organisation (WHO) performance status of 0-1.\n8. Neurologically stable (e.g., without a progression of neurological symptoms or requiring escalating doses of systemic steroid therapy within the last week).\n9. Written (signed or dated) informed consent and be capable of co-operating with treatment and follow up.\n10. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week prior to the first dose of either IMP:\n\n    Haemoglobin (Hb): ≥ 10.0 g\u002FdL Absolute neutrophil count: ≥ 1.5 x 10\\^9\u002FL Platelet count: ≥ 75 x 10\\^9\u002FL Coagulation: INR \\\u003C1.5 and APTT \\\u003C1.5x if not anticoagulated INR stable \\> 7 days within intended therapeutic range if anticoagulated Bilirubin: ≤ 1.5 x ULN; subjects with Gilbert's syndrome can enrol if conjugated bilirubin is within normal limits.\n\n    Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): \\\u003C 3 x ULN Albumin: ≥ 28 g\u002FL Creatinine: \\\u003C1.5 x ULN and creatinine clearance \\> 45 ml\u002Fmin as measured or calculated based on Cockcroft-Gault formula Sodium: ≥ 130 mmol\u002FL Potassium, Calcium, Magnesium, phosphate: Within institution normal ranges (replacement is permitted) Urinary protein: \\\u003C 1+ on dipstick\n11. Female patients with reproductive potential must have a negative serum, or urine, pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study.\n12. A participant must be either of the following: a. not of childbearing potential, b. of child-bearing potential and practicing true abstinence during the entire period of the study, including up to 6 months after the last dose of the study treatment is given, or c. of childbearing potential and practicing 2 methods of contraception, including 1 highly effective user independent method and a second method, to avoid impregnating a partner or becoming pregnant, respectively. A participant must agree to continue contraception throughout the study, and for at least 6 months after the last dose of study treatment.\n\n    Please, refer to section 4.1 of CTFG guidance \"Recommendations related to contraception and pregnancy testing in clinical trials\" and to section 9.6 of the Master Protocol for further details.\n\n    Note: If the childbearing potential changes after start of the study (eg, participant of childbearing potential who is not heterosexually active becomes active, premenarchal participant experiences menarche) the participant must begin birth control, as described above.\n13. A participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study treatment.\n14. A participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 6 months after receiving the last dose of study treatment. A participant who is sexually active with a partner of childbearing potential must agree to use a condom with spermicidal foam\u002Fgel\u002Ffilm\u002Fcream\u002Fsuppository and their partner must also be practicing a highly effective method of contraception (ie, established use of oral, injected, or implanted hormonal methods of contraception; placement of an intrauterine device \\[IUD\\] or intrauterine hormone-releasing system \\[IUS\\]). If the participant is vasectomized, they must still use a condom (with or without spermicide) for prevention of passage of exposure through ejaculation, but their partner is not required to use contraception.\n15. A participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after receiving the last dose of study treatment.\n16. A participant must be willing and able to adhere to the lifestyle restrictions specified in this protocol.\n\nExclusion Criteria for Phase 1b:\n\n1. Receipt of treatment before the first dose of study drug (Cycle 1 Day 1) within an interval shorter than the following, as applicable:\n\n   * Cytotoxic chemotherapy during the prior 2 weeks or 6 weeks for nitrosoureas\n   * Bevacizumab during the prior 6 weeks\n   * Five half-lives of any small molecule investigational or licensed medicinal product.\n2. Prior immune checkpoint inhibitor therapy or vaccine therapy is not permitted. Prior EGFR-targeting therapy is not permitted. Prior use of any other immune-modulatory investigational agent must be discussed with sponsor team and CI.\n3. Ongoing Grade 2 or greater toxicities from pre-existing conditions or from previous treatments.\n4. Patients with carcinomatous meningitis, leptomeningeal spread of tumour, spread of tumour to the brain stem or spinal cord.\n5. Has evidence of recent intratumoural or peritumoural haemorrhage on baseline MRI. Patients with radiological findings that are stable on at least 2 consecutive MRI scans at least 3 weeks apart will be eligible.\n6. History of clinically relevant bleeding disorders, including significant gastrointestinal (GI) bleeding within last 6 months.\n7. Participant has active cardiovascular disease including, but not limited to:\n\n   * A medical history of deep venous thrombosis or pulmonary embolism within 1 month prior to first dose of study drug or any of the following within 6 months prior to first dose of study drug: myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary\u002Fperipheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis such as non-obstructive catheter-associated thrombus, incidental or asymptomatic pulmonary embolism, are not exclusionary. Patients on Warfarin will need to be converted onto low-molecular weight-based heparin therapy.\n   * Participant has a significant genetic predisposition to venous thromboembolic (VTE) events such as Factor V Leiden.\n   * Participant has a prior history of VTE and is not on appropriate therapeutic anticoagulation as per National Comprehensive Cancer Network (NCCN) or local guidelines.\n   * Uncontrolled (persistent) hypertension: systolic blood pressure \\> 160 mm Hg; diastolic blood pressure \\> 100 mm Hg.\n   * Congestive heart failure (CHF), defined as New York Heart Association (NYHA) class III-IV or hospitalization for CHF (any NYHA class) within 6 months of first dose of the study drug.\n   * Concurrent and clinically significant abnormalities on ECG at Screening, including a corrected QT interval (QTcF \\> 460ms).\n8. History of malabsorption syndrome or other conditions that may interfere with enteral absorption. Patients with a history of or active inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis). Patients with acute or chronic pancreatitis. History of GI perforation or fistulae.\n9. Has urine protein \\> 1g\u002F24 hours. Participants with \\> 1+ on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria.\n10. Has significant lung disease including pneumonitis, interstitial lung disease (including drug-induced or radiation ILD\u002Fpneumonitis), idiopathic pulmonary fibrosis, cystic fibrosis, active tuberculosis, or history of opportunistic infections (including PCP or Cytomegalovirus (CMV) pneumonia).\n11. Participant is serologically positive for hepatitis B surface antigen (HbsAg), Note: participants with a prior history of hepatitis B virus (HBV) demonstrated by positive hepatitis B core antibody are eligible if they have at Screening 1) a negative HBsAg and 2) a HBV DNA (viral load) below the lower limit of quantification, per local testing. Subjects with a positive HBsAg due to recent vaccination are eligible if HBV DNA (viral load) is below the lower limit of quantification, per local testing.\n12. Participant is serologically positive for hepatitis C antibody. Note: participants with a prior history of hepatitis C virus (HCV), who have completed antiviral treatment and have subsequently documented HCV RNA below the lower limit of quantification per local testing are eligible.\n13. Participant has other clinically active infectious liver disease.\n14. Participant is positive for human immunodeficiency virus (HIV), with 1 or more of the following:\n\n    * Receiving antiretroviral therapy (ART) that may interfere with study treatment (consult sponsor for review of medication prior to enrolment).\n    * CD4 count \\\u003C 350 at screening\n    * AIDS-defining opportunistic infection within 6 months of start of screening\n    * Not agreeing to start ART and be on ART \\> 4 weeks plus having HIV viral load \\\u003C 400 copies\u002FmL at end of 4-week period (to ensure ART is tolerated and HIV controlled).\n15. Participant has an uncontrolled illness, including but not limited to:\n\n    * Uncontrolled diabetes\n    * Ongoing or active infection (includes infection requiring treatment with antimicrobial therapy \\[participants will be required to complete antibiotics 1 week prior to starting study treatment\\] or diagnosed or suspected viral infection.\n    * active bleeding diathesis\n    * Impaired oxygenation requiring continuous oxygen supplementation\n    * Psychiatric illness, social situation, or any other circumstances that would limit compliance with study requirements\n    * Any ophthalmologic condition that is clinically unstable\n16. Steroid requirement for neurological symptom control of \\> 3mg Dexamethasone per day (patients will allowed to enrol if they have been on a stable dose of steroids of equivalent or less than 3mg Dexamethasone for at least 5 days prior to Day 1 of Cycle 1).\n17. Has received a live vaccine within 30 days of planned start of study therapy. Note: inactive vaccines including COVID vaccines are allowed prior to 1 week of Day 1 of Cycle 1).\n18. Concurrent or prior malignancy other than the disease under study. The following exceptions require consultation with the Chief Investigator:\n\n    1. Non-muscle invasive bladder cancer (NMIBC) treated within the last 24 months that is considered completely cured.\n    2. Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is completely cured.\n    3. Non-invasive cervical cancer treated within the last 24 months that is considered completely cured.\n19. Is a participant or plans to participate on another interventional clinical trial while taking part in this Phase 1 study. Participation in an observational trial would be acceptable.\n20. A participant has major surgery excluding placement of vascular access or tumour biopsy, or had significant traumatic injury within 4 weeks before first dose of study drug or minor surgery within 2 weeks, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study. Note: Participants with planned surgical procedures to be conducted under local anaesthesia may participate.\n21. A participant has palliative radiotherapy within 1 week of the firs dose of study drug,\n22. Any other condition which in the investigator's opinion would not make the patient a good candidate for the clinical trial.",{"count":115,"type":20},12,[23],"The purpose of this clinical trial is to evaluate the safety and tolerability of amivantamab and to determine the preliminary antitumour activity of amivantamab administered at the recommended Phase 2 dose (RP2D). In the Phase 1b of this study a biomarker defined arm will be opened, initially in the relapsed GMB setting, enrolling 12 patients. These patients will be treated with amivantamab monotherapy. Amivantamab will be administered intravenously (IV) weekly for the first 4 weeks, then every 2 weeks thereafter until disease progression or unacceptable toxicity. The first dose will be given as a split infusion, 350 mg IV over 4 hours on cycle 1 day 1 and 1400 mg IV over 6 hours on cycle 1 day 2. Subsequent infusions are given at a dose of 1750 mg IV over 2-5 hours in cycle 1 and between 2-3 hours from cycle 2 onwards if the first dose was well-tolerated with no significant toxicity.\n\nProgression to Phase 2 is dependent on emergent data and funding.",[95,94,69,93],"2025-04-23",{"date":121,"type":36},"2025-04-25",{"date":123,"type":36},"2024-10-09",{"date":125,"type":20},"2027-03-05",{"name":104,"class":43},2]