Objective
High-grade gliomas are the most frequent type of primary brain tumor in adults. Despite optimal multi-modality treatment the disease almost always recurs, at which point median survival is less than a year. Vorinostat (suberoylanilide hydroxamic acid) is the first member of a new class of anti-cancer compounds - histone deacetylase (HDAC) inhibitors, that modulate global gene expression. The drug potentiates the anti-cancer activity of cytotoxic agents in a range of tumor types. The standard dosing schedule is low-dose drug for a long-duration. Recently ‘high-dose short-duration’ vorinostat in combination with chemotherapy has been shown to be well tolerated by subjects with colon cancer and leukemia.
Radiation therapy kills cancer cells by inflicting DNA damage. Vorinostat potentiates radiation induced cell death (radiosensitization) through down-regulation of DNA repair. Clinical trials assessing combined low-dose vorinostat and radiation are in progress. In this proposal we investigate short-duration very high-dose vorinostat in combination with hypofractionated radiation therapy (RT) for recurrent glioma.
Method: A phase I dose-escalation trial for subjects with recurrent glioma scheduled to undergo surgery followed by RT. Vorinostat will be administered both before surgery and post-operatively concurrently with RT. Tissue removed at surgery (exposed to vorinostat) will be compared with previously resected tumor from the same patient at the time of original diagnosis (unexposed to vorinostat), enabling analysis of how the drug modulates the levels of DNA repair enzymes. The overall goal of the proposal is to demonstrate the feasibility and biological rationale for this combined modality approach in recurrent glioma, laying the groundwork for a subsequent randomized phase II trial. Exploratory analyses will attempt to correlate response with DNA repair enzyme expression – a possible stratification factor in future trials.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine surgery
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine oncology colorectal cancer
- medical and health sciences clinical medicine oncology leukemia
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2011-CIG
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
52621 Ramat Gan
Israel
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.