Track topics on Twitter Track topics that are important to you
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as temsirolimus, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib and temsirolimus may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving sorafenib together with temsirolimus may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of temsirolimus when given together with sorafenib and to see how well they work in treating patients with recurrent glioblastoma.
- Establish a maximum tolerable dose of temsirolimus in combination with sorafenib in patients with recurrent glioblastoma not receiving enzyme-inducing anticonvulsants (EIACs). (Phase I [closed to accrual as of 11/21/07])
- Define the safety profile of temsirolimus and sorafenib in these patients. (Phase I [closed to accrual as of 11/21/07])
- Assess the evidence of antitumor activity. (Phase I [closed to accrual as of 11/21/07])
- Assess the efficacy, as measured by progression-free survival, of temsirolimus and sorafenib in patients with recurrent glioblastoma not receiving EIACs . (Phase II)
- Assess the safety and toxicities of this regimen in these patients. (Phase II)
- Correlate tumor and blood biomarkers with clinical outcome of patients treated with temsirolimus and sorafenib.
- Evaluate tumor tissue specimens for evidence of bioactivity of these agents.
OUTLINE: This is a multicenter, phase I (closed to accrual as of 11/21/07), dose-escalation study of temsirolimus followed by a phase II open-label study.
- Phase I (closed to accrual as of 11/21/07): Patients receive oral sorafenib twice daily on days 1-28 and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients are assigned to 1 of 2 treatment groups.
- Group 1 (patients not undergoing surgery): Patients receive sorafenib and temsirolimus as in phase I (closed to accrual as of 11/21/07) at the MTD.
- Group 2 (patients undergoing surgery): Patients receive oral sorafenib twice daily on days 1-8 (15 doses) and temsirolimus IV at the MTD on day 1. Patients undergo surgery on day 8. After recovering from surgery, patients receive sorafenib and temsirolimus as in phase I (closed to accrual as of 11/21/07) at the MTD.
- Group 3 (patients who have received prior anti-VEGF therapy and are not undergoing surgery): Patient receive sorafenib and temsirolimus as in phase I (closed to accrual as of 11/21/07) at the MTD.
Biopsy or resected tissue and blood are collected prior to treatment (usually at diagnosis) and analyzed for biomarkers.
After completion of study treatment, patients are followed every 6 months for 5 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 141 patients will be accrued for this study.
Masking: Open Label, Primary Purpose: Treatment
Brain and Central Nervous System Tumors
sorafenib tosylate, temsirolimus
Mayo Clinic Scottsdale
National Cancer Institute (NCI)
Published on BioPortfolio: 2014-08-27T03:44:27-0400
RATIONALE: 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 s...
RATIONALE: Temsirolimus and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving temsirolimus together with sorafenib tosyla...
RATIONALE: Sorafenib and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib may also stop the growth of tumor cells by blocki...
RATIONALE: Sorafenib may stop the growth of tumor cells by stopping blood flow to the tumor and by blocking the enzymes necessary for their growth. PURPOSE: This phase I trial is studying...
RATIONALE: 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 ...
Hemangioblastomas (HBs) are benign vascular tumors of the central nervous system and histologically contain abundant microvessels. Therefore, they clinically exhibit vascular malformation-like charact...
Central nervous system (CNS) tumors are a leading cause of death in pediatric oncology. New drugs are desperately needed to improve survival. We evaluated the outcome of children and adolescents with ...
The aim of this study is to review the effects of thymoquinone (TQ) against central nervous systems (CNS) tumors.
Multiple cerebral gliomas (MCGs), usually classified into multifocal and multicentric subtypes, represent major diagnostic challenges as their clinical, radiologic, and pathohistological features are ...
Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.
A group of malignant tumors of the nervous system that feature primitive cells with elements of neuronal and/or glial differentiation. Use of this term is limited by some authors to central nervous system tumors and others include neoplasms of similar origin which arise extracranially (i.e., NEUROECTODERMAL TUMORS, PRIMITIVE, PERIPHERAL). This term is also occasionally used as a synonym for MEDULLOBLASTOMA. In general, these tumors arise in the first decade of life and tend to be highly malignant. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2059)
Diseases of the parasympathetic or sympathetic divisions of the AUTONOMIC NERVOUS SYSTEM; which has components located in the CENTRAL NERVOUS SYSTEM and PERIPHERAL NERVOUS SYSTEM. Autonomic dysfunction may be associated with HYPOTHALAMIC DISEASES; BRAIN STEM disorders; SPINAL CORD DISEASES; and PERIPHERAL NERVOUS SYSTEM DISEASES. Manifestations include impairments of vegetative functions including the maintenance of BLOOD PRESSURE; HEART RATE; pupil function; SWEATING; REPRODUCTIVE AND URINARY PHYSIOLOGY; and DIGESTION.
The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.
A vascular anomaly characterized by a radial or wedge-shaped arrangement of dilated VEINS draining into a larger vein in the brain, spinal cord, or the meninges. Veins in a venous angioma are surrounded by normal nervous tissue, unlike a CENTRAL NERVOUS SYSTEM CAVERNOUS HEMANGIOMA that lacks intervening nervous tissue. Drainage of venous angioma is fully integrated with the body's venous system, therefore, in most cases there is no clinical signs and rare bleeding.
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...
Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...