[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"gliosarcoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:gliosarcoma":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,5,0,[8,47,81,106,129],{"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":28,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":35,"lastUpdatePostDateStruct":36,"startDateStruct":39,"completionDateStruct":41,"leadSponsor":43,"locationsCount":46},"100587938","phase-1-study-of-abbv-637-or-abbv-155-with-eras-801-for-people-with-glioblastoma-100587938",false,"NCT06934889","Study of ABBV-637 or ABBV-155 With ERAS-801 for People With Glioblastoma","Phase Ib Trial of ABBV-637 or ABBV-155 in Combination With ERAS-801 for Glioblastoma With Amplification of the Epidermal Growth Factor Receptor","Inclusion Criteria:\n\n* Patients must be 18 years of age or older at the time of consent signing.\n* All Patients must have WHO Grade IV Glioblastoma\u002FGliosarcoma using WHO 2021 criteria and include the diagnosis of molecular GBM, recurrent patients must be progressive or recurrent following radiation therapy +\u002F- chemotherapy\n* Patients must be IDH wild type by CLIA-certified laboratory assay available at time of consent.\n* Patients must have evidence of EGFR gene amplification by CLIA-certified laboratory assay at time of consent.\n* Patients must have measurable disease as per RANO criteria pre-operatively (there is no requirement for post-operative disease to be present or absent). \\[cohort A\u002FB only\\]\n* Patients must be able to tolerate MRIs\n* Patients may have no more than 2 prior therapy regimens. \\[cohort A\u002FB only\\]\n* Patients must have recovered from severe toxicity of prior therapy. The following intervals from previous treatments are required to be eligible:\n\n  1. 12 weeks from the completion of radiation\n  2. 6 weeks from a nitrosourea chemotherapy\n  3. 3 weeks from a non-nitrosourea chemotherapy\n  4. 4 weeks from any investigational (not FDA-approved) agents\n  5. 6 months from the last treatment with bevacizumab\n  6. 2 weeks or 5 half-lives from administration of a non-cytotoxic, Chemotherapies other than bevacizumab, whichever is shorter\n* Patients must be undergoing surgery that is clinically indicated as determined by their care providers. \\[cohort A\u002FB only\\] Patients must be eligible for surgical resection according to the following criteria:\n\n  a. Expectation that the surgeon is able to resect at least 500 mg of tumor from enhancing tumor with low risk of inducing neurological injury.\n* Paraffin embedded tissue must be available from initial surgical resection at diagnosis (prior to any treatment). The following amount of tissue is requested: 1 formalin-fixed, paraffin embedded (FFPE) tissue block (preferred) or 10 FFPE unstained slides (5µm thick).\n* Patients must have a Karnofsky Performance Status (KPS) ≥60% (i.e. the patient must be able to care for himself\u002Fherself with occasional help from others).\n* Patients must have the following organ and marrow function:\n\n  1. Absolute neutrophil count \\>1,200\u002FmcL\n  2. Platelets \\>100,000\u002FmcL\n  3. Hemoglobin \\> 9 g\u002FdL .\n  4. Total bilirubin ≤ institutional upper limit of normal, or ≤ 3.0 mg\u002FdL for subjects with Gilbert's syndrome\n  5. AST (SGOT) and ALT (SGPT) ≤ 3 × institutional upper limit of normal\n  6. Creatinine ≤ institutional upper limit of normal OR Creatinine clearance \\>60 ml\u002Fmin\u002F1.73m2 for patients with creatinine levels above institutional normal\n  7. APTT\u002FPTT ≤ 1.5 x institutional upper limit of normal\n* Echocardiogram with ejection fraction ≥ 50% and no other clinically significant finding that, in the opinion of the investigator, would increase the subject's susceptibility to cardiac toxicity.\n\n  a. If ECHO cannot be performed for structural or safety reasons, a MUGA may be obtained instead after discussion with treating investigator.\n* Patients must have a 12-lead electrocardiogram performed within 2 weeks of treatment start with QT interval corrected for heart rate (QTc) \\\u003C 450 msec (using Fridericia's correction), and no clinically significant abnormalities. (Cohorts A, B, E \\& F only)\n* Women of childbearing potential must have a negative serum pregnancy test prior to study entry. Women of childbearing potential and men treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months after completion of treatment administration. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.\n* A negative serum pregnancy test for all female subjects (except postmenopausal) at the screening visit and a negative urine pregnancy test for all female subjects (except postmenopausal) at baseline before the first dose of study drug.\n* If female, subject must be either postmenopausal, OR permanently surgically sterile OR, for women of childbearing potential, practicing at least 1 protocol-specified method of birth control that is effective from study Day 1 through at least 4 months after the last dose of study drug.\n* If male, and subject is sexually active with female partner(s) of childbearing potential, he must agree from study Day 1 through 4 months after the last dose of study drug to practice the protocol-specified contraception.\n* If female, subject must not be pregnant, breastfeeding, or considering becoming pregnant during the study while receiving study drug and for at least 4 months after the last dose of study drug.\n* If male, subject must not be considering fathering a child or donating sperm during the study or for 4 months after the last dose of study drug.\n* No known active viral hepatitis infection (including hepatitis B and C) or human immunodeficiency virus (HIV) with the following exceptions:\n\n  * Subjects with a history of hepatitis B that is considered cured may be enrolled at the discretion of the treating investigator.\n  * Subjects with a history of hepatitis C that is considered cured with definitive therapy may be enrolled at the discretion of the treating investigator.\n  * Subjects with HIV and undetectable viral load, so long as ongoing antiretroviral therapy does not pose risk of adverse drug-drug interactions, at the discretion of the treating investigator.\n* Patients must have no concurrent malignancy that requires active therapy.\n* Patients must be able to swallow medication by mouth, either tablets or dispersed in solution.\n\nExclusion Criteria:\n\n* Patients may not be receiving any other investigational agents.\n* Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the investigational agents are ineligible.\n* Patients with prior therapy with EGFR targeting agents are ineligible because treatment with EGFR kinase inhibitors or other EGFR-targeted agents has the potential to deplete the tumor of EGFR-amplified or EGFR mutant cell populations and confound the evaluation of the investigational regimen. Patients would only be eligible if surgery on a recurrence after the EGFR-targeted therapy confirmed persistence of an EGFR alteration.\n* Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol. Patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs. Patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of study drug(s).\n* Patients must not have evidence of significant hematologic, renal, or hepatic dysfunctioPatients must not have evidence of significant intracranial hemorrhage (For example, in the recurrent setting, circumstances where the intracranial hemorrhage would obscure the amount and quality of tissue obtained at the time of the on-treatment surgery).\n* Patients with uncontrolled intercurrent illness including, but not limited to, hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002F social situations that would limit compliance with study requirements, are ineligible.\n* Participants with clinically significant cardiovascular disease including, but not limited to:\n\n  * No recent history (within 6 months) of congestive heart failure (defined as New York Heart Association, Class 2 or higher), ischemic cardiovascular event, cardiac arrhythmia requiring pharmacological or surgical intervention, pericardial effusion, or pericarditis.\n  * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, e.g., complete left bundle branch block, second- or third-degree heart block, PR-interval \\> 250 ms.\n  * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, or any concomitant medication know to prolong the QT interval.\n* No history of clinically significant medical and\u002For psychiatric conditions or any other reason that, in the opinion of the investigator, would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug\n* Pregnant women are excluded from this study because the investigational regimens have potential for teratogenic or abortifacients effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated on this study.\n* HIV-positive patients on strong CYP3A4 inducers or inhibitors are ineligible because of the potential for pharmacokinetic interactions.\n* Patients who have acute or currently active\u002Frequiring anti-viral therapy hepatic or biliary disease are ineligible (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases from the primary brain tumor, or stable chronic liver disease per investigator assessment).\n* Patients receiving P-gp inhibitors\u002FP-gp substrates with narrow therapeutic index are ineligible.\n* Patients who are receiving a drug that has a risk of QTc prolongation with known risk of if QTc is ≥ 460 msec. are ineligible. (Temozolomide is allowed for cohorts C,D, E and F)\n* Subject must not have systemically used known moderate or strong cytochrome P450 (CYP)3A inhibitors within 10 days before the first dose of study drug and throughout the study.\n* Subject must not have received any live vaccine within 2 weeks before the first dose of study drug, or be expected to need a live vaccination during study participation including at least 4 weeks after the last dose of study drug.","ALL","18 Years",{"count":19,"type":20},60,"ESTIMATED","INTERVENTIONAL",[23],"PHASE1","The researchers are doing this study to find out whether the drugs ABBV-637 and ABBV-155 are safe treatments that cause few or mild side effects when given alone or in combination with ERAS-801 in people with recurrent GBM.",[26,27],"Glioblastoma","Gliosarcoma",[29,30,31,32,33],"WHO grade IV","ABBV-637","ABBV-155","ERAS-801","24-409","RECRUITING","2026-06-09",{"date":37,"type":38},"2026-06-10","ACTUAL",{"date":40,"type":38},"2025-04-07",{"date":42,"type":20},"2028-04",{"name":44,"class":45},"Memorial Sloan Kettering Cancer Center","OTHER",11,{"id":48,"slug":49,"hasResults":11,"nctId":50,"briefTitle":51,"officialTitle":52,"acronym":4,"eligibilityCriteria":53,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":54,"targetDuration":4,"studyType":21,"phases":56,"briefSummary":58,"conditions":59,"keywords":63,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":71,"lastUpdatePostDateStruct":72,"startDateStruct":74,"completionDateStruct":76,"leadSponsor":78,"locationsCount":80},"100505680","phase-2-phase-2a-immune-modulation-with-ultrasound-for-newly-diagnosed-glioblastoma-100505680","NCT05864534","Phase 2a Immune Modulation With Ultrasound for Newly Diagnosed Glioblastoma","A Phase 2a Trial of Immune Modulation in Combination With Ultrasound-mediated Blood Brain Barrier Opening in Patients With Newly Diagnosed Glioblastoma","Inclusion Criteria:\n\n* Have newly diagnosed pathologically proven glioblastoma, isocitric dehydrogenase-1\u002F2 wild-type\n* Tumor with methyl guanine methyl transferase (MGMT) gene promoter unmethylated\n* Available paraffin embedded tumor tissue for the study\n* Have completed standard radiotherapy with or without temozolomide\n* 18 years of age or older\n* Able to undergo contrast-enhanced MRI\n* Have an Eastern Cooperative Oncology Group\u002FWorld Health Organization performance status ≤ 2\n* Size and location of the residual tumor and\u002For resection cavity must allow to be able to be covered by the sonication field\n* Have not received any prior treatment with immunotherapeutic agents treatments for glioblastoma or other indications\n* Have the ability to understand and willingness to sign a written informed consent prior to registration on study.\n* Be willing and able to comply with the protocol.\n* Have adequate organ and bone marrow function\n* Agree to use adequate contraception if appropriate\n\nExclusion Criteria: Patients will be ineligible if they have:\n\n* Multifocal tumor (unless all localized in a 50-mm diameter area accessible to ultrasound field) or tumor located in the posterior fossa.\n* Uncontrolled epilepsy.\n* Received other investigational agents within 2 weeks of registration\n* Received prior therapy with or have history of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in this study.\n* Contraindication to checkpoint inhibitor therapy (e.g., history of autoimmune disease)\n* Uncontrolled illness\n* History of active malignancy other than the brain tumor within 12 months prior to registration.\n* Are pregnant or breastfeeding.",{"count":55,"type":20},25,[57],"PHASE2","Brain tumor treatment is hampered by the blood-brain barrier (BBB). This barrier prevents drugs carried in the bloodstream from getting into the brain. If the BBB can be opened, making it temporarily more permeable, drugs may able to better reach the brain tumor. In this trial we will implant a novel device with 9 ultrasound emitters, allowing temporary and reversible opening of the BBB to maximize brain penetration of drugs that modulate the immune system. The device will be implanted after radiation is completed. Immune modulating drugs will be given every 3 weeks in conjunction with activation of the device to open the BBB.\n\nThe objectives of this trial are to establish whether it is safe and feasible to administer immune modulating drugs in this manner, and identify whether the treatment is effective in treating glioblastoma.",[60,61,27,62],"Newly Diagnosed Glioblastoma","Glioblastoma, Isocitric Dehydrogenase (IDH)-Wildtype","Glioblastoma Multiforme",[64,65,66,67,68,69,70],"Immunotherapy","Ultrasound","Blood-brain barrier","Sonocloud","Balstilimab (BAL)","Botensilimab (BOT)","Doxorubicin (DOX)","2026-05-08",{"date":73,"type":38},"2026-05-13",{"date":75,"type":38},"2024-01-19",{"date":77,"type":20},"2031-08-31",{"name":79,"class":45},"Northwestern University",1,{"id":82,"slug":83,"hasResults":11,"nctId":84,"briefTitle":85,"officialTitle":86,"acronym":4,"eligibilityCriteria":87,"healthyVolunteers":11,"sex":16,"minAge":88,"maxAge":4,"enrollmentInfo":89,"targetDuration":4,"studyType":21,"phases":91,"briefSummary":92,"conditions":93,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":97,"lastUpdatePostDateStruct":98,"startDateStruct":100,"completionDateStruct":102,"leadSponsor":104,"locationsCount":80},"100492928","phase-1-a-study-of-temodar-with-abexinostat-pci-24781-for-patients-with-recurrent-glioma-100492928","NCT05698524","A Study of Temodar With Abexinostat (PCI-24781) for Patients With Recurrent Glioma","A Phase I Study of Metronomic Temozolomide With Abexinostat (PCI-24781) for Patients With Recurrent High Grade Glioma","Inclusion Criteria:\n\n* Pathologically proven diagnosis of high grade (aka grade III or IV) glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, glioblastoma, gliosarcoma)\n* Prior radiation therapy and standard temozolomide; additional therapies for previous progressions are eligible (prior bevacizumab and Optune are allowed)\n* Three or more months from the end of chemoradiotherapy or have biopsy or imaging consistent with disease progression\n* 19 years of age or older (the age of consent in Nebraska)\n* Fully recovered from any toxicity of prior therapy that, in the opinion of the investigator, could impact tolerance to the study drug\n* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2\n* Adequate bone marrow reserve (ANC count ≥1,500\u002Fmm3, hemoglobin \\> 8 g\u002FdL, platelet count ≥100,000\u002Fmm3)\n* Adequate renal function (a serum creatinine that is at or below 2.0 mg\u002FdL)\n* Adequate hepatic function (serum AST and ALT less than 1.5 times the upper limits of normal, serum alkaline phosphatase less than 2.5 times the upper limits of normal)\n* Able to provide written, informed consent\n* Females of child-bearing potential must have a negative pregnancy test within 7 days of initiating study (non-child bearing potential is defined as age 55 years or older and no menses for two years or any age with surgical removal of the uterus and\u002For both ovaries)\n* Females of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and up to 6 months following treatment\n\nExclusion Criteria:\n\n* Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of oral PCI-24781\u002FAbexinostat, or put the study outcomes at undue risk\n* Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmia, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification\n* Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction\n* Immunotherapy, chemotherapy, radiotherapy, corticosteroids (at dosages equivalent to prednisone \\> 20 mg\u002Fday) or experimental therapy (other than PCI-24781\u002FAbexinostat PO) within 4 weeks before first dose of study drug\n* Concurrent use of enzyme-inducing antiepileptic drugs (phenytoin, phenobarbital, carbamazepine, felbamate, topiramate and oxcarbazepine)\n* Any other active malignancy other than nonmelanoma skin cancer or controlled prostate cancer\n* Known history of Human Immunodeficiency Virus (HIV) or active infection with Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV) or any uncontrolled active systemic infection (no testing is required for eligibility)\n* Creatinine \\> 1.5 x institutional upper limit of normal (ULN); total bilirubin \\> 1.5 x ULN (unless from Gilbert's disease), and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \\> 2.5 x ULN\n* Pregnant or breast-feeding\n* Baseline ECG duration of the ventricular action potential corrected for heart rate (QTc interval) prolongation based on Fridericia's formula is \\> 450 ms in males and \\> 470 ms in females\n* Concomitant valproic acid use, or another histone deacetylases (HDAC) inhibitor\n* Receiving treatment with following medications and unable to discontinue treatment or switch medications prior to study enrollment:\n\n  * Amiodarone (Cordarone, Pacerone)\n  * Arsenic trioxide (Trisenox)\n  * Chlorpromazine (Aralen)\n  * Cisapride (Propulsid)\n  * Clarithromycin (Biaxin)\n  * Disopyramide (Norpace)\n  * Dofetilide (Tikosyn)\n  * Doperidol (Inapsine)\n  * Erythromycin (EryTab, Erythrocin)\n  * Flecanide (Tambocor)\n  * Haloperidol (Haldol)\n  * Ibutilide (Corvert)\n  * Methadone (Methadose, Dolophine)\n  * Moxifloxacin (Avelox)\n  * Pentamidine (Pentam, Nebupent)\n  * Pimozide (Orap)\n  * Procainamide (Procan, Pronestyl)\n  * Quinidine (Cardioquin, Quinaglute)\n  * Sotalol (Betapace)\n  * Thioridazine (Mellaril)\n  * Vandetanib (Zactima)","19 Years",{"count":90,"type":20},24,[23],"Glioblastoma (GBM), WHO grade IV glioma, represents the majority of adult malignant primary brain tumors, with an incidence of 2-3 per 100,000 person-years. The survival for GBM has increased in the last decade but is still low with a median survival of 15-18 months. Recurrence after initial standard therapy, radiation therapy and chemotherapy with temozolomide, few options are available. Even with further therapy, median progression free survival at 6 months after first relapse (PFS-6) is only 15%. Similarly, anaplastic astrocytoma and anaplastic oligodendroglioma, grade III gliomas, once recurrent after radiation therapy and first-line chemotherapy, have identical therapeutic options and poor outcomes with PFS-6 of 31%. Temozolomide (TMZ) has a favorable side effect profile and is available orally, however, cytotoxicity occurs. Metronomic temozolomide at low doses on a continuous schedule, have demonstrated better survival in studies. This study will determine the recommended dose and the side effects of PCI-24781\u002FAbexinostat with metronomic temozolomide.",[94,95,96,26,27],"Recurrent High Grade Glioma","Anaplastic Astrocytoma","Anaplastic Oligodendroglioma","2026-04-13",{"date":99,"type":38},"2026-04-17",{"date":101,"type":38},"2023-06-26",{"date":103,"type":20},"2029-07",{"name":105,"class":45},"University of Nebraska",{"id":107,"slug":108,"hasResults":11,"nctId":109,"briefTitle":110,"officialTitle":111,"acronym":4,"eligibilityCriteria":112,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":113,"targetDuration":4,"studyType":115,"phases":4,"briefSummary":116,"conditions":117,"keywords":118,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":120,"lastUpdatePostDateStruct":121,"startDateStruct":123,"completionDateStruct":125,"leadSponsor":127,"locationsCount":80},"100497418","improving-understanding-of-glioblastoma-through-preservation-of-biologically-active-brain-tissue-100497418","NCT05756985","Improving Understanding of Glioblastoma Through Preservation of Biologically Active Brain Tissue","Improving Understanding of Glioblastoma Through Preservation of Biologically Active Brain Tissue (PRESERVE GBM)","Inclusion Criteria:\n\n1. Have the appearance of high-grade glioma on magnetic resonance (MR) imaging if allowed to consent and will undergo the procedure if the frozen is consistent with glioblastoma or gliosarcoma OR Patients with a history of histologically confirmed diagnosis of World Health Organization Grade glioblastoma or gliosarcoma that are undergoing repeat resection of a recurrent tumor as identified on preoperative MR imaging\n2. Aged ≥ 18 years old\n3. Contrast-enhancing tumor volume of at least 10 cc on the preoperative, volumetric MRI within 1 month prior to surgery\n4. Provision of signed and dated informed consent form by participant or legally authorized representative (LAR), if applicable\n\nExclusion Criteria:\n\n1\\. Has a history or current evidence of any medical condition, therapy, or laboratory abnormality that might confound the results of the study or is not in the best interest of the participant, in the opinion of the treating investigator.",{"count":114,"type":20},120,"OBSERVATIONAL","To collect and preserve glioblastoma tissue during standard of care tumor resection surgery and blood for future molecular and genetic testing. Tissue for research will be collected from three different regions within the same tumor to study how these regions differ in their structure, DNA, and RNA and also to compare the data obtained from this testing to imaging data found in the medical record. The goal of this study is to help us better understand what the glioblastoma tumor tissue looks like and how it functions. This understanding can lead to new therapies for the treatment of glioblastoma in the future.",[26,62,27],[119],"specimen banking","2026-02-02",{"date":122,"type":38},"2026-02-04",{"date":124,"type":38},"2024-12-11",{"date":126,"type":20},"2029-01",{"name":128,"class":45},"Baptist Health South Florida",{"id":130,"slug":131,"hasResults":11,"nctId":132,"briefTitle":133,"officialTitle":134,"acronym":4,"eligibilityCriteria":135,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":136,"targetDuration":4,"studyType":21,"phases":138,"briefSummary":139,"conditions":140,"keywords":141,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":146,"lastUpdatePostDateStruct":147,"startDateStruct":149,"completionDateStruct":151,"leadSponsor":153,"locationsCount":80},"100445745","phase-1-study-of-pembrolizumab-and-m032-nsc-733972-100445745","NCT05084430","Study of Pembrolizumab and M032 (NSC 733972)","A Phase I\u002FII Study of Pembrolizumab and M032 (NSC 733972), a Genetically Engineered HSV-1 Expressing IL-12, in Patients With Recurrent\u002FProgressive and Newly Diagnosed Glioblastoma Multiforme, Grade 3 or Grade 4 Astrocytoma, or Gliosarcoma","Inclusion Criteria:\n\nPhase I\u002FCohort I: Participants are eligible to be included in the study only if all of the following criteria apply:\n\nPatients must have histologically or cytologically confirmed glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma, and is deemed a potential candidate for resection of the recurrent tumor.\n\nPrior therapy: Patients must have failed external beam radio-therapy to the brain, and if eligible and tolerated, undergone appropriate treatment with temozolomide chemotherapy. All radiation and additional chemotherapies must have been completed at least 4 weeks prior to enrollment. Prior therapy with nitrosoureas must have been completed at least 6 weeks prior to enrollment.\n\nPhase I\u002FCohort II or Phase II: Participants are eligible to be included in the study only if all of the following criteria apply:\n\nPatient must have MRI findings consistent with probable malignant glioma, have no previous diagnosis of glioma, and have had either no history of any surgery for brain tumor. The exception to this requirement is that patients who have under-gone biopsy for diagnosis only and have not received any other treatment. All patients must be potential candidates for resection of the probably malignant glioma tumor.\n\nShould a patient in Phase I\u002FCohort II or Phase II be found on final pathologic diagnosis to not have a glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma, he\u002Fshe will receive no other doses of M032 other than that administered at the time of craniotomy, nor will he\u002Fshe receive any doses of Pembrolizumab. He\u002Fshe will be followed for evidence of toxicity of M032 only and will be considered off-study for all efficacy and other secondary endpoints.\n\nAll patients, whether in Phase I\u002FCohort II or Phase II shall also be required to meet the following eligibility and be subject to the exclusion criteria below:\n\n1. Age ≥18 years. Because no dosing or adverse event data are currently available on the use of M032 in patients \\\u003C16 years of age, children are excluded from this study but will be eligible for future pediatric phase 1 single-agent trials.\n2. Karnofsky Performance Status (KPS) ≥70% (see Appendix B).\n3. Life expectancy of greater than 4 weeks.\n4. Preoperatively, the lesion must be ≥1.0 cm in diameter as determined by MRI.\n5. The effects of M032 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for six months after receiving the final dose of M032. Because it is currently unknown if M032 can be transmitted by sexual contact, a barrier method of birth control must be employed and for six (6) months following the administration of the last dose of this study drug. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately. Subjects should also refrain from donating blood during the trial.\n6. Ability to understand and the willingness to sign a written informed con-sent document.\n7. Females of childbearing potential must not be pregnant; this will be con-firmed by a negative serum pregnancy test within 14 days prior to starting study treatment.\n8. Patients must have normal organ and marrow function as defined below:\n\n   1. leukocytes……………………. \\>3,000\u002Fμl\n   2. absolute neutrophil count………. \\>1,500\u002Fμl\n   3. platelets…………………………... \\>100,000\u002Fμl\n   4. total bilirubin……………………. within normal institutional limits\n   5. AST(SGOT)\u002FALT(SGPT)………… \\\u003C2.5 X institutional upper limit of normal creatinine within normal institutional limits Or\n   6. creatinine clearance……………... \\>60 mL\u002Fmin\u002F1.73 m2 for patients with creatinine levels above insti-tutional normal\n\n      Exclusion Criteria:\n\n      A Woman of Child Bearing Potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to allocation.(see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.\n\n      Has received prior therapy with an anti-PD-1, anti-PD-L1, or antiPDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137).\n\n      Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation.\n\n      Note: Participants must have recovered from all adverse events (AEs) due to previous thera-pies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.\n\n      Note: If participant received major surgery, they must have recovered adequately from the toxicity and\u002For complications from the intervention prior to starting study treatment.\n\n      Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella\u002Fzoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.\n\n      Is currently participating in or has participated in a study of an interventionally-directed investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.\n\n      Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent or if the agent is directed at analysis and not treatment (e.g., certain PET tracers, etc.).\n\n      Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 2 mg daily of dexamethasone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.\n\n      Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.\n\n      Has severe hypersensitivity (≥Grade 3) to pembrolizumab and\u002For any of its excipients.\n\n      Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pitu-tary insufficiency, etc.) is not considered a form of systemic treatment.\n\n      Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.\n\n      Has an active infection requiring systemic therapy.\n\n      Has a known history of Human Immunodeficiency Virus (HIV).\n\n      Has a known history of Hepatitis B (defined as Hepatitis B surface anti-gen \\[HBsAg\\] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.\n\n      Has a known history of active Bacillus Tuberculosis (TB).\n\n      Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.\n\n      Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.\n\n      Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening vis-it through 120 days after the last dose of trial treatment.\n\n      Patients who have had chemotherapy, cytotoxic therapy, immunotherapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas), surgical resection within 4 weeks prior to entering the study, or have received experimental viral therapy or gene therapy at any time (e.g., adenovirus, retrovirus or herpes virus protocol). However, this does not preclude re-treatment with M032 at a later date.\n\n      Patients who have not recovered from adverse events due to therapeutic interventions administered more than 4 weeks earlier.\n\n      History of allergic reactions attributed to compounds of similar biologic composition to M032 or to IL-12.\n\n      Tumor involvement which would require ventricular, brainstem, basal ganglia, or posterior fossa inoculation or would require access through a ventricle in order to deliver treatment.\n\n      History of encephalitis within the past 5 years, any history of multiple sclerosis or other CNS infection. Bacterial infections associated with previous cranial operations such as bone flap infections, cerebral abscesses, etc., that have been completely treated will not be exclusions for this trial\n\n      For Phase I, Cohort I: Required steroid increase within 2 weeks of scheduled M032 administration. All study candidates: When possible, the patient should be on a dexamethasone equivalent dose of ≤ 2mg daily at the time of treatment.\n\n      Active herpes lesion.\n\n      Concurrent therapy with any drug active against HSV (acyclovir, valacyclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir).\n\n      Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any other medical condition that precludes surgery.\n\n      Patients with known history of allergic reaction to IV contrast material that is not amenable to pre-treatment by protocol.\n\n      Patients with pacemakers, ferro-magnetic aneurysm clips, metal infusion pumps, metal or shrapnel fragments or certain types of stents.\n\n      Receipt of Gliadel Therapy.\n\n      Receipt of Bevacizumab (Avastin) therapy within 4 weeks of scheduled M032 administration. (Receipt of Bevacizumab (Avastin) greater than 4 weeks of scheduled M032 administration does not exclude patient.",{"count":137,"type":20},28,[23,57],"This Phase I (Cohort I and Cohort II) and Phase II trial is designed to confirm the safety and tolerability of Pembrolizumab when given in conjunction with M032, an Oncolytic Herpes Simplex Virus (oHSV) that expresses IL-12 and perform the Phase II portion using a Recommended Phase 2 Dose (RP2D) of M032 (provided by the Phase I) when given in conjunction with Pembrolizumab for recurrent malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, or glio-sarcoma).",[62,95,27],[142,143,144,145],"Recurrent","Progressive","M032","Pembrolizumab","2026-01-20",{"date":148,"type":38},"2026-01-22",{"date":150,"type":38},"2022-02-25",{"date":152,"type":20},"2028-03-01",{"name":154,"class":45},"University of Alabama at Birmingham"]