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This phase II clinical trial is studying how well RO4929097 works in treating patients with recurrent or progressive glioblastoma. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth
I. 6-month progression-free survival (PFS6) (Group A) II. Efficiency of neurosphere generation after pretreatment with RO4929097. (Group B)
I. Radiographic response rate. (Group A) II. Toxicities associated with this regimen. (Group A) III. Overall survival. (Group A) IV. Expression levels of Notch pathway components and downstream targets. (Group B) V. Tumor propagation. An extension of lifespan by 50% in tumor bearing mice (mice bearing fresh tumor tissue). (Group B) VI. Patient event-free survival in correlation with expression levels of Notch pathway components and downstream targets.
VII. 6-month progression-free survival (PFS6). VIII. Toxicities associated with this regimen. IX. Overall survival.
OUTLINE: Patients are assigned to 1 of 2 treatment groups.
Group A: Patients receive oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, 15-17, and 22-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group B (surgical resection indicated): Patients receive oral gamma-secretase inhibitor RO4929097 once daily on days -6 to -1. Patients undergo surgical resection on day 0. Within 30 days after surgical resection, patients receive gamma-secretase inhibitor RO4929097 as in group A.
After completion of study treatment, patients are followed up every 2 months.
Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Adult Giant Cell Glioblastoma
gamma-secretase/Notch signalling pathway inhibitor RO4929097, therapeutic conventional surgery, pharmacological study, laboratory biomarker analysis
Adult Brain Tumor Consortium
Active, not recruiting
National Cancer Institute (NCI)
Published on BioPortfolio: 2014-07-23T21:09:05-0400
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Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PROTEIN precursors. PSEN2 mutations cause ALZHEIMER DISEASE type 4.
Integral membrane proteins and essential components of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PROTEIN precursors. Mutations of presenilins lead to presenile ALZHEIMER DISEASE with onset before age 65 years.
Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PROTEIN precursors. PSEN1 mutations cause early-onset ALZHEIMER DISEASE type 3 that may occur as early as 30 years of age in humans.
A disintegrin and metalloproteinase domain-containing protein that cleaves the membrane-bound precursor of TUMOR NECROSIS FACTOR-ALPHA to its mature form. It cleaves several other CELL SURFACE PROTEINS, including INTERLEUKIN-1 RECEPTOR TYPE II; TRANSFORMING GROWTH FACTOR ALPHA; L-SELECTIN; MUCIN-1; and AMYLOID BETA-PROTEIN PRECURSOR. It can also function as an activator of the Notch signaling pathway by mediating the cleavage of NOTCH RECEPTORS.
An analogue of GAMMA-AMINOBUTYRIC ACID. It is an irreversible inhibitor of 4-AMINOBUTYRATE TRANSAMINASE, the enzyme responsible for the catabolism of GAMMA-AMINOBUTYRIC ACID. (From Martindale The Extra Pharmacopoeia, 31st ed)
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...