Safety Study of XL184 (Cabozantinib) in Combination With Temozolomide and Radiation Therapy in the...
GlioblastomaGiant Cell Glioblastoma1 moreThe purpose of this study is to determine the highest safe dose of XL184 administered orally in combination with temozolomide (TMZ, Temodar®) and radiation therapy (RT). XL184 is a new chemical entity that inhibits VEGFR2, MET, and RET, kinases implicated in tumor formation, growth and migration. Temozolomide (TMZ, Temodar®) is an orally administered alkylating agent. It is approved by the Food and Drug Administration (FDA) for the treatment of newly diagnosed glioblastoma (GB) patients when given in combination with radiation therapy (RT) followed by maintenance treatment. First-line treatment for patients with GB consists of a concurrent phase (6-7 weeks in duration) during which TMZ is given with RT, followed by a rest phase (4 weeks in duration; to allow for recovery from delayed toxicity, if present), and a maintenance phase, during which patients receive TMZ for approximately twelve 28-day cycles. To determine the highest safe dose, subjects will receive different amounts of XL184 at different times according to the phase of TMZ and radiation therapy. The first group of subjects will receive the lowest dose of XL184. As long as no medically unacceptable side effects are noted, the dose will be increased for the next group. If the dose is not well-tolerated by the first group of subjects, the dose will be lowered for the next group.
Temsirolimus, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma...
Adult Giant Cell GlioblastomaAdult Glioblastoma1 moreThis phase I trial is studying the side effects and best dose of temsirolimus when given together with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma multiforme. Temsirolimus 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving temsirolimus together with temozolomide and radiation therapy may kill more tumor cells.
Sorafenib Combined With Erlotinib, Tipifarnib, or Temsirolimus in Treating Patients With Recurrent...
Adult Giant Cell GlioblastomaAdult Glioblastoma2 moreThis phase I/II trial is studying the side effects and best dose of erlotinib, tipifarnib, and temsirolimus when given together with sorafenib and to see how well they work in treating patients with recurrent glioblastoma multiforme or gliosarcoma. Sorafenib, erlotinib, tipifarnib, and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib and tipifarnib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with erlotinib, tipifarnib, or temsirolimus may kill more tumor cells.
Lapatinib in Treating Young Patients With Recurrent or Refractory Central Nervous System Tumors...
Recurrent Childhood Anaplastic AstrocytomaRecurrent Childhood Brain Stem Glioma6 moreThis phase I/II trial studies lapatinib to see how well it works in treating young patients with recurrent or refractory central nervous system (CNS) tumors. Lapatinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.
A Phase I/II Trial of BMS-247550 for Treatment of Patients With Recurrent High-Grade Gliomas
Adult Anaplastic AstrocytomaAdult Giant Cell Glioblastoma2 moreDrugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. This phase I/II trial is studying the side effects and best dose of ixabepilone and how well it works in treating patients with recurrent glioma.
Erlotinib in Treating Patients With Recurrent Malignant Glioma or Recurrent or Progressive Meningioma...
Adult Anaplastic AstrocytomaAdult Anaplastic Oligodendroglioma7 morePhase I/II trial to study the effectiveness of erlotinib in treating patients who have recurrent malignant glioma or recurrent or progressive meningioma. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.
Safety Study of AP23573 in Patients With Progressive or Recurrent Glioma (8669-023)(COMPLETED)
Malignant GliomaGlioblastoma1 moreA Phase I, open-label, non-randomized, sequential dose escalation cohort trial of the safety, tolerability, and maximum tolerated dose (MTD) of AP23573 when administered intravenously as a 30-minute infusion, once daily for five days, repeated every two weeks, to patients with progressive or recurrent malignant glioma.
Evaluate the Safety and Effectiveness of Intranasal Administration of Temozolomide in Patients With...
GliomaMalignant2 moreThe purpose of this pilot study is to determine the safety, tolerability, and the maximum tolerated dose intranasal administration of temozolomide (TMZ) as a single agent in Treatment on the patients with GBM. Intranasal administration is a new method of treating brain tumours for the direct administration of drugs, inhibitors or viruses, with minimal involvement of the BBB. The investigators know the orally prescribed standard chemotherapy temozolomide (TMZ) is widely used to treat glioma tumours. Received evidence of safety and efficacy in a full cycle of preclinical trials (on GLP Standart) and tests of calculated doses of intranasal administration of TMZ in healthy volunteers. Intranasal administration of temozolomide is considered as GBM therapy, which provides direct access to a therapeutic dose of the drug into the brain (to the neoplastic process) with low toxicity
Pilot Study Using Amide Proton Transfer Magnetic Resonance Imaging Distinguishing Glioma
GliosarcomaGliomaThis research is being done to study the pattern of changes in various parts of the magnetic resonance imaging (MRI) studies that patients have done to help plan their radiation therapy and to evaluate the effects of therapy. The MRI of the brain is one of the major ways a participant's doctors determine how to treat a participant's tumor and if the participant's tumor is growing or not. In this study the investigators want to learn if new sequences added to the MRI that the investigators are already getting to guide partipants' radiation treatment can be analyzed to help make better treatment decisions. MRI sequences that examine the composition and structure of the tissues in the brain in a different way will be obtained. These are called called Amide Proton Transfer (APT) and Diffusion Weighted MRI. These scans will first be performed at the time of participants' radiation plannings scan done before treatment and near the end of the course of radiation treatments. This will allow the study team to investigate if there are changes in these sequences before radiation treatment and to see if using these MRI studies will allow us to better plan radiation treatments for patients in the future. This pre-treatment scan will be done at the same time as participants' standard radiation planning MRI, but will cause the scan to take longer. Participants will also have an extra MRI during one of the last 5 days of the planned 28-33 radiation treatments that are standardly used. This additional scan will not include administration of injected contrast agents, and would occur on a day when participants are also coming in for radiation. This scan will be compared with the first scan. The investigators will determine whether these changes may predict later long term outcome of treatment for patients. Patients who enroll in this study will get all of the standard therapy they would get for their tumor whether or not they participate in this study. There is no extra or different therapy given. The investigators anticipate that the radiation treatment volumes created using APT will largely overlap with the conventional plan but will be distinct at the margins. Disease failure is more likely to occur in areas with APT abnormalities suggestive of active tumor. In patients that have failure outside the contrast enhancing area, the region of failure will be predicted by regions of increased APT activity. Current MRI sequences do not allow for prediction of regions of recurrence or progression, or distinguish between tumor, pressure, or surgical injury as the cause of FLAIR/T2 abnormalities. Disease failure is more likely to occur in areas with APT abnormalities suggestive of active tumor. In patients that have failure outside the contrast enhancing area, the region of failure will be predicted by regions of increased APT activity. Current MRI sequences do not allow for prediction of regions of recurrence or progression, or distinguish between tumor, pressure, or surgical injury as the cause of FLAIR/T2 abnormalities. Volume containing elevated APT signal may be associated with outcome (survival). In an exploratory analysis, the investigators will evaluate whether there are characteristic patterns that should be prospectively studied in a larger trial.
Study of the IDO Pathway Inhibitor, Indoximod, and Temozolomide for Pediatric Patients With Progressive...
Glioblastoma MultiformeGlioma6 moreThis is a first-in-children phase 1 trial using indoximod, an inhibitor of the immune "checkpoint" pathway indoleamine 2,3-dioxygenase (IDO), in combination with temozolomide-based therapy to treat pediatric brain tumors. Using a preclinical glioblastoma model, it was recently shown that adding IDO-blocking drugs to temozolomide plus radiation significantly enhanced survival by driving a vigorous, tumordirected inflammatory response. This data provided the rationale for the companion adult phase 1 trial using indoximod (IND#120813) plus temozolomide to treat adults with glioblastoma, which is currently open (NCT02052648). The goal of this pediatric study is to bring IDO-based immunotherapy into the clinic for children with brain tumors. This study will provide a foundation for future pediatric trials testing indoximod combined with radiation and temozolomide in the up-front setting for patients with newly diagnosed central nervous system tumors.