Active clinical trials for "Glioblastoma"

The study is a prospective, single arm open label study, designed to test the to evaluate the tolerability and safety outcome of newly diagnosed GBM patients treated with NovoTTF-200A concomitant to Radiotherapy/Temozolomide followed by Temozolomide. The device is a portable, battery operated device for chronic administration of alternating electric fields (termed TTFields or TTF) to the region of the malignant tumor, by means of surface, insulated electrode arrays.

This phase IB/II trial is designed to investigate the safety and survival benefits for patients with recurrent glioblastoma with unmethylated MGMT promoter treated with Bortezomib and Temozolomide in a specific schedule.

This research study is studying a new schedule of radiation therapy for recurrent glioblastoma as a possible treatment for this diagnosis. This radiation schedule is based on a new model for radiation resistance in glioblastoma. The name of the radiation schedule involved in this study is: - Re-irradiation for glioblastoma using a novel Mathematical Model-Adapted Radiation Fractionation Schedule

This is a Phase II study in a single center to determine the efficacy of autologous dendritic cells (DCs) loaded with autogeneic glioma stem-like cells (A2B5+) administered as a vaccination in adults with glioblastoma multiforme (primary or secondary).

The investigators hypothesize that the rate of radiologically complete resections of contrast-enhancing brain tumors following surgeries aided by use of 5-ALA induced fluorescence guidance and use of an intraoperative ultra-low field MRI is higher compared to surgeries aided by 5-ALA induced fluorescene alone.

Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Despite maximal treatment tumor relapse occurs regularly accompanied by unfavourable prognosis. Among other reasons, it is believed that this could be in part due to the existence of the so-called tumor stem cells (TSCs), a cellular subfraction within GBM which escape therapy by being highly resistant to irradiation and chemotherapy and thus constituting the source of tumor recurrence. GBM, like many other cancers, show a sub-population of aldehyde dehydrogenase (ALDH) overexpressing TSCs. More specifically, ALDH1A1, a cytoplasmatic isoform of ALDH, proved to be a novel stem cell marker in human GBM. In addition, ALDH1A1 has been shown to be a mediator for resistance of GBM to temozolomide (TMZ) and a reliable predictor of clinical outcome; prognosis of patients with a high level of ALDH1A1 expression was poor compared with that of patients with low levels. Consequently, ALDH1A1 may serve as a potential target to improve treatment of human GBM through inhibition of the enzyme. Disulfiram (DSF) has been used for more than sixty years in the treatment of chronic alcoholism because of the unpleasant symptoms it provokes after ethanol intake. The underlying mechanism is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the liver ALDHs. Actually, DSF is a strong inhibitor of ALDH1A1 and relatively non-toxic at therapeutic (for chronic alcoholism) doses that can penetrate the blood-brain barrier. In addition, DSF has been shown to be cytotoxic on GBM stem-like cells, inhibiting the growth of TMZ resistant GBM cells and blocking self-renewal by ~100% , while it has been identified as an inhibitor of human GBM stem cells in high-throughput chemical screens. Interestingly, a number of these actions were copper-dependent. In the current Phase II clinical trial, DSF/copper combination will be tested as an adjunctive and concurrent chemotherapy in the treatment of newly diagnosed GBM. According to our hypothesis, initiation of DSF chemotherapy after the resection of the tumor and before the introduction of the standard radio-chemotherapy will inhibit ALDH1A1 of GBM TSCs making them more susceptible to radio-chemotherapy and possibly reducing the recurrence rate of GBM. On the other hand, the addition of copper will probably enhance the cytotoxic effects of DSF possibly through augmentation of its pro-apoptotic and proteasomal inhibitory actions.

Trial Hypothesis: Acute, progressing lethal neurooncological process can be transferred into chronic and non-lethal, the survival rates and life quality can be improved by of control of tumor cells (TCs) quantity and targeted regulation of effector functions of tumor stem cells (TSCs). Brief Description: The first line therapy of glioblastoma multiforme (GBM) involves allogeneic haploidentical hematopoietic stem cells (HSCs), dendritic vaccine (DV) and cytotoxic lymphocytes (CTLs). TCs and TSCs are isolated from GBM sample. Dendritic cells are isolated from peripheral blood mononuclear cells and cultured. Tumor sample provides tumor specific antigens to prepare DV. CTLs are obtained from peripheral blood after DV administrations. HSCs are harvested from closely related donor after granulocyte-colony-stimulating factor (G-CSF) administration. Allogeneic HSCs are administered intrathecally 5 times every 2 weeks, at day 1, 14, 28, 42, 56. DV is given 3 times every 2 weeks (day 14, 28, 42) subcutaneously in four points. CTLs are administered every 2 weeks for 3 months, then 3 times every 1 month intrathecally. Six months after the therapy completion, the efficiency is evaluated and the cohort demonstrating efficiency continues the therapy, while cohort demonstrating no efficiency is transferred to active comparator arm. Second line therapy involves DV with recombinant proteins, CTLs and autologous HSC with modified proteome. Autologous HSCs are mobilized by G-CSF. Carcinogenesis-free intracellular pathways of signal transduction able to respond to targeted regulation of therapeutic cell systems with specific properties, are detected in TSCs using complete transcriptome profiling of gene expression, proteome mapping and profiling of proteins, bioinformation and mathematical analysis and mathematical modeling of protein profiles. To find key oncospecific proteins in TSCs and TCs, the targets for TSCs regulation are detected, as well as protein ligands able to regulate reproductive and proliferative properties of TSCs. Using these data of TCs and TSCs proteins, the cell preparations to initiate adoptive immune response are prepared: DV loaded with recombinant proteins analogous to key tumor antigens, CTLs and autologous proteome-modified HSCs. Autologous proteome-modified HSCs, DV and CTLs are administered as in the first line therapy.

Simultaneous integrated boost (SIB), a field-in-field escalation technique, has been introduced to deliver higher radiation dose to the certain part of target with the same fractionation scheme. The aim of this study was to investigate the value of chemoradiation (CCRT) using SIB in glioblastoma and the correlation with surgical extent.

Bradmer Pharmaceuticals, Inc. (Bradmer) is requesting approval to study the safety of Neuradiab® when combined with Bevacizumab (Avastin) therapy given at a minimum of 30 days after Neuradiab administration in patients with a first or second recurrence of glioblastoma multiforme (GBM), in an attempt to manage life threatening recurrence of Grade IV malignant glioma.

GERT is a one-armed single-center phase I/II trial. In a first step, dose-escalation of TMZ from 50 mg/m2 to 75mg/m2 together with radiotherapy and cetuximab will be performed. Should safety be proven, the phase II trial will be initiated with the standard dose of 75mg/m2 of TMZ. Cetuximab will be applied in the standard application dose of 400mg/m2 in week 1, thereafter at a dose of 250mg/m2 weekly. A total of 46 patients will be included into this phase I/II trial. Primary endpoints are feasibility and toxicity, secondary endpoints are overall and progression-free survival. An interim analysis will be performed after inclusion of 15 patients into the main study. Patients' enrolment will be performed over a period of 2 years. The observation time will end 2 years after inclusion of the last patient.