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Oxidative Phosphorylation Targeting In Malignant Glioma Using Metformin Plus Radiotherapy Temozolomide
Tailored approaches targeting crucial oncogenes and pathways have shown successful results in a number of cancer types and offer exciting perspective in neuro-oncology. IDH (Isocitrate dehydrogenase) wild-type (IDHwt) glioblastoma (GBM) (10%) present a unique and homogenous energetic metabolism which is specifically dependent on the oxidative phosphorylation (OXPHOS) rather than on the aerobic glycolysis. OXPHOS+ IDHwt GBMs overexpress mitochondrial markers and can be specifically inhibited by mitochondrial inhibitors in vitro and in vivo. Metformin is an oral inhibitor of mitochondrial complex I and is a widely used drug in diabetic and non-diabetic patients, safe and well...
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Paxalisib With a High Fat, Low Carb Diet and Metformin for Glioblastoma
This study is for patients with newly diagnosed glioblastoma, as well as patients who have recurring glioblastoma. Subjects will be given daily paxalisib and metformin while also maintaining a ketogenic diet. The purpose of this study is to assess the safety of Paxalisib while maintaining a ketogenic diet (a high fat, low carbohydrate diet) and Metformin (a drug approved by the Food and Drug Administration to treat type 2 diabetes), and to see what effects it has on glioblastoma.
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Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG
Indoximod was developed to inhibit the IDO (indoleamine 2,3-dioxygenase) enzymatic pathway, which is important in the natural regulation of immune responses. This potent immune suppressive mechanism has been implicated in regulating immune responses in settings as diverse as infection, tissue/organ transplant, autoimmunity, and cancer. By inhibiting the IDO pathway, we hypothesize that indoximod will improve antitumor immune responses and thereby slow the growth of tumors. The central clinical hypothesis for the GCC1949 study is that inhibiting the pivotal IDO pathway by adding indoximod immunotherapy during chemotherapy and/or radiation is a potent approach for breaking immune...
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Peposertib and Radiation Therapy, Followed by Temozolomide for the Treatment of Patients With Newly Diagnosed MGMT Unmethylated Glioblastoma or Gliosarcoma
This phase I trial investigates the side effects and best dose of Peposertib, and to see how well it works in combination with radiation therapy in treating patients with newly diagnosed MGMT unmethylated glioblastoma or gliosarcoma. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Peposertib may further stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving Peposertib with radiation therapy may work better...
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Personalized Cancer Stem Cell High-Throughput Drug Screening for Glioblastoma
Proposed treatment of subjects with newly diagnosed glioblastoma with novel personalized drug regimens identified to be effective in vitro using cancer stem cells derived from their individual tumors, alongside standard of care radiation and TMZ.
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Personalized Functional Profiling in Metastatic Gastrointestinal Cancer or Recurrent Glioblastoma Patients in Luxembourg.
The investigators are developing a novel standardized and centralized approach named Integrated Personalized Functional Profiling (PFP) in Luxembourg. Based on recent improvements in cancer biopsy-derived 3D-culture technologies the PFP process will screen patient derived cells (PDCs) with FDA/EMA-approved drugs to generate personalized functional response profiles. The selected drug through PFP technology will provide personalized treatment recommendation for the patient. This pilot study will evaluate the clinical feasibility of setting-up an effective workflow as a first step. Outcomes from this study will be used subsequently to help plan the clinical validation of the...
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Personalized NeoAntigen Cancer Vaccine w RT Plus Pembrolizumab for Patients With Newly Diagnosed GBM
This research study is studying a new type of vaccine as a possible treatment for patients with glioblastoma. This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the intervention to use for further studies. "Investigational" means that the intervention is being studied and that research doctors are trying to find more about it. It also means that the FDA (U.S. Food and Drug Administration) has not approved the Personalized NeoAntigen Cancer Vaccine for any use in patients, including people with glioblastoma. The purpose of the initial study cohort (Cohort 1) is to determine if...
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Personalized Targeted Glioblastoma Therapies by ex Vivo Drug Screening
Patient derived cell line (PDC) -based drug screening will be applied to formulate a personalized treatment approach.
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PET-imaging of Two Vartumabs in Patients With Solid Tumors
VARTUTRACE is a first-in-human PET/CT molecular imaging study in patients with solid tumors. This study will investigate the biodistribution and pharmacology of two antibody fragments binding oncofetal Chondroitin Sulfate (CS). Oncofetal CS are tumor-specific carbohydrate motifs present in proteoglycans and identified by VAR2 Pharmaceuticals as expressed during fetal development. Oncofetal CS reappears in the vast majority of cancers while remaining largely absent from normal tissues. VAR2 Pharmaceuticals recently developed antibodies specific for oncofetal CS. VARTUTRACE uses two of these as radiolabeled antibody fragments to study biodistribution, tumor accumulation,...
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Phase 1 Open-label Study of 123I-ATT001 in Subjects with Relapsed Glioblastoma
Phase I open-label trial of 123I-ATT001 monotherapy and in combination with treatment therapies in subjects with relapsed glioblastoma.