Top Read: Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma.

Br J Cancer. 2014 May 27;110(11):2655-61. doi: 10.1038/bjc.2014.209. Epub 2014 May 1.

Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma.

Abstract

Background:Sorafenib (Sb) is a multiple kinase inhibitor targeting both tumour cell proliferation and angiogenesis that may further act as a potent radiosensitizer by arresting cells in the most radiosensitive cell cycle phase. This phase I open-label, noncontrolled dose escalation study was performed to determine the safety and maximum tolerated dose (MTD) of Sb in combination with radiation therapy (RT) and temozolomide (TMZ) in 17 patients with newly diagnosed high-grade glioma.Methods:Patients were treated with RT (60 Gy in 2 Gy fractions) combined with TMZ 75 mg m(-2) daily, and Sb administered at three dose levels (200 mg daily, 200 mg BID, and 400 mg BID) starting on day 8 of RT. Thirty days after the end of RT, patients received monthly TMZ (150-200 mg m(-2) D1-5/28) and Sb (400 mg BID). Pharmacokinetic (PK) analyses were performed on day 8 (TMZ) and on day 21 (TMZ&Sb) (Clinicaltrials ID: NCT00884416).Results:The MTD of Sb was established at 200 mg BID. Dose-limiting toxicities included thrombocytopenia (two patients), diarrhoea (one patient) and hypercholesterolaemia (one patient). Sb administration did not affect the mean area under the curve(0-24) and mean Cmax of TMZ and its metabolite 5-amino-imidazole-4-carboxamide (AIC). Tmax of both TMZ and AIC was delayed from 0.75 (TMZ alone) to 1.5 h (combined TMZ/Sb). The median progression-free survival was 7.9 months (95% confidence interval (CI): 5.4-14.55), and the median overall survival was 17.8 months (95% CI: 14.7-25.6).Conclusions:Although Sb can be combined with RT and TMZ, significant side effects and moderate outcome results do not support further clinical development in malignant gliomas. The robust PK data of the TMZ/Sb combination could be useful in other cancer settings.

New Clinical Trial:Minimally Invasive Surgery Plus rt-PA for ICH Evacuation Phase III (MISTIE III)

See All Stroke Trials

The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, is looking for individuals to participate in clinical studies.  Participating in clinical trials allows you to play an active role in research on the nature and causes of many disorders of the brain and nervous system, and to possibly help physician-scientists develop future treatments.  The information below is designed to help you quickly learn about actively recruiting research studies for which you or someone you know may be eligible.

Description:

The purpose of this study is to test a minimally invasive surgical procedure with a drug called rt-PA (recombinant tissue plasminogen activator) as a treatment for intracerebral hemorrhage (ICH).

ICH occurs when a blood vessel in part of the brain bursts open, causing blood to leak into the brain and clot.  Currently, there is no standard treatment for ICH and most people with ICH face a long recovery and have long term deficits.

MISTIE III will test a minimally invasive surgical procedure in which a hollow tube, called a catheter, is used to remove the blood clot and administer rt-PA into the ICH to break up the blood clot.  Rt-PA is the standard treatment for ischemic stroke (a type of stroke in which a blood vessel is blocked by a clot).

Five hundred participants will be randomly assigned to one of two groups:  medical treatment or surgical treatment.  In the medical group, participants will receive standard medical interventions for treating ICH.  In the surgical group, participants will undergo a minimally invasive surgical procedure to put in place a catheter that will be used to administer rt-PA directly into the blood clot.  After being assigned to a study group, participants will be monitored in the hospital for seven days.  During this time, the medical group will receive the best currently available ICH treatments.  The surgical group will receive up to 9 doses of rt-PA through the catheter every eight hours plus the same care the medical group receives.  Both groups will have daily computed tomography (CT) brain scans.

Participants will be followed for a year after their ICH to determine if the surgical procedure and rt-PA will help them to recover more fully.  Follow-up will include three outpatient visits to the clinic and two telephone interviews.

Knowledge gained from this study may provide scientists with information on how to better treat ICH.

 

Eligibility Criteria:

Please follow this link for trial eligibility information to share with your doctor.

Study Design:

Interventional

Study Locations:

Multiple locations worldwide

For more information:

Contact:  Amanda Bistran-Hall; Tel: 410-955-2536, email:  abistran1@jhmi.edu; or Karen Lane, CMA; Tel: 410-614-3461; email: klane@jhmi.edu; or visit: http://clinicaltrials.gov/ct2/show/NCT01827046 orwww.braininjuryoutcomes.com External link

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