Active clinical trials for "Glioma"

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether temozolomide is more effective when given with or without bevacizumab in treating patients with recurrent glioma. PURPOSE: This randomized clinical trial is studying how well temozolomide works with or without bevacizumab in treating patients with recurrent glioma.

Treatment of patients with recurrent glioma includes neurosurgical resection, chemotherapy, or radiation therapy. In most cases, a full course of radiotherapy has been applied after primary diagnosis, therefore application of re-irradiation has to be applied cautiously. With modern precision photon techniques such as fractionated stereotactic radiotherapy (FSRT), a second course of radiotherapy is safe and effective and leads to survival times of 22, 16 and 8 months for recurrent WHO grade II, III and IV tumors. Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the Glioblastoma (GBM) cell line as well as the endpoint analyzed. Protons, however, offer an RBE which is comparable to photons. First Japanese Data on the evaluation of carbon ion radiation therapy for the treatment of primary high-grade gliomas showed promising results in a small and heterogeneous patient collective. In the current Phase I/II-CINDERELLA-trial re-irradiation using carbon ions will be compared to FSRT applied to the area of contrast enhancement representing high-grade tumor areas in patients with recurrent gliomas. Within the Phase I Part of the trial, the Recommended Dose (RD) of carbon ion radiotherapy will be determined in a dose escalation scheme. In the subsequent randomized Phase II part, the RD will be evaluated in the experimental arm, compared to the standard arm, FSRT with a total dose of 36 Gy in single doses of 2 Gy. Primary endpoint of the Phase I part is toxicity. Primary endpoint of the randomized part II is survival after re-irradiation at 12 months, secondary endpoint is progression-free survival.

An open-label phase 2, multicenter study in participants with recurrent malignant glioma.

The purpose of this study is to determine the safety and tolerability of XL765 in combination with Temozolomide in adults with anaplastic gliomas or glioblastoma on a stable Temozolomide maintenance dose. XL765 is a new chemical entity that inhibits the kinases PI3K and mTOR. In preclinical studies, inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells, whereas inactivation of mTOR has been shown to inhibit the growth of tumor cells. Temozolomide (TMZ, Temodar®) is an orally administered alkylating agent with activity against malignant gliomas. It is approved by the Food and Drug Administration for the following indications: 1) treatment of newly diagnosed glioblastoma multiforme (GBM) patients when given concomitantly with radiotherapy and then as maintenance treatment; 2) refractory anaplastic astrocytoma (AA), ie, patients who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine. Temozolomide is commonly used in the treatment of other anaplastic gliomas (AG) including oligodendroglial tumors and mixed gliomas.

The phase I portion of study is designed to determine the Maximum Tolerated Dose (MTD) of BSI-201 with two clinically relevant dosing regimens of temozolomide (TMZ). Secondary objectives in the phase I trial include determining the PK of BSI-201 in malignant glioma patients and correlating BSI-201 PK with degree of PARP-1 inhibition. A safety run-in will confirm the safety of BSI-201 added to standard TMZ and radiation therapy and the phase II portion of the study will assess the efficacy and tolerability of the MTD dose of BSI-201 with daily TMZ and radiation therapy followed by adjuvant TMZ in patients with newly diagnosed GBM and assess overall survival as the primary outcome measure. Information on each phase of the study will be listed when each phase opens for enrollment. Based on data generated by BiPar/Sanofi, it is concluded that iniparib does not possess characteristics typical of the PARP inhibitor class. The exact mechanism has not yet been fully elucidated, however based on experiments on tumor cells performed in the laboratory, iniparib is a novel investigational anti-cancer agent that induces gamma-H2AX (a marker of DNA damage) in tumor cell lines, induces cell cycle arrest in the G2/M phase in tumor cell lines, and potentiates the cell cycle effects of DNA damaging modalities in tumor cell lines. Investigations into potential targets of iniparib and its metabolites are ongoing.

RATIONALE: Specialized radiation therapy, such as proton beam radiation therapy, that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. PURPOSE: This phase I/II trial is studying the best way to give proton beam radiation therapy and to see how well it works in treating patients with low grade gliomas.

This phase I trial is studying the side effects and best dose of ABT-888 when given in combination with temozolomide in treating young patients with recurrent or refractory CNS tumors. ABT-888 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving ABT-888 together with temozolomide may kill more tumor cells.

This is a single-institution Phase I/II study designed to evaluate the safety and induction of an immune response, and preliminary clinical response of vaccinations with Type-1 alpha-DCs (alpha-DC1) loaded with glioma-associated antigen (GAA) epitopes and administration of poly-ICLC in patients with recurrent malignant gliomas. Approximately 30 subjects will be enrolled in this study at UPMC/UPCI Hillman Cancer Center. The study participants in this trial will be HLA-A2 positive male or female adults over 18 years of age. The primary objective is to establish the safety of this approach. The endpoints will be to determine the maximum tolerated dose (MTD) of alpha-DC1 vaccines in combination with a fixed dose of poly-ICLC, using standard criteria and close clinical followups. The secondary objectives are 1) to assess the immunological response against GAAs in patients with recurrent malignant gliomas immunized with DCs loaded with GAA-derived peptides using enzyme-linked immuno-spot (ELISPOT), delayed-type hypersensitivity (DTH) and tetramer assays; and 2) to assess the preliminary anti-tumor clinical activity of the vaccines as measured by radiological response (MRI), overall survival, and 4- and 6-month progression-free survival (PFS).

This phase I trial is studying the side effects and best dose of vorinostat when given together with bortezomib in treating young patients with refractory or recurrent solid tumors, including CNS tumors and lymphoma. Vorinostat and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

The outcome for children with high-grade gliomas and diffuse intrinsic brainstem gliomas remains poor despite the use of multi-modal therapy with surgery, radiation therapy and chemotherapy.