Track topics on Twitter Track topics that are important to you
A recent study by Plotkin et al. showed that bevacizumab (Avastin) treatment was followed by clinically meaningful hearing improvement, tumor-volume reduction, or both in some, but not all, patients with Vestibular Schwannoma (VS) who were at risk for complete hearing loss or brain-stem compression from growing VS. Because of the promising results in preliminary studies of Bevacizumab and because of significant experience with the safety of the dosages proposed in this study, this study will offer a safe treatment for patients with VS. Therefore, this phase I clinical research trial will test the hypothesis that Bevacizumab can be safely used by direct intracranial superselective intraarterial infusion up to a dose of 10mg/kg to ultimately enhance survival and hearing function of patients with VS.
Newer techniques in interventional neuroradiology have allowed for a more selective delivery of catheters higher up into the arterial tree where agents such as chemotherapies, can be delivered without the risk of adverse affects such as blindness. In fact, studies here at Cornell have developed very new and exciting super selective intraarterial delivery treatment for Retinoblastoma and Malignant Glioma brain tumors with little toxicity. Therefore, this trial will ask one simple question: Is it safe to deliver a first dose of Avastin intraarterially using these super selective delivery techniques instead of the standard intravenous route of administration? This should not only increase the amount of drug that gets to the VS but also spare them of any adverse effects from a less selective delivery. During that single dose of intraarterial Avastin, they will also receive a dose of mannitol that opens up the blood brain barrier to improve delivery of the agent to the tumor. After that single dose of Mannitol and Avastin intraarterially, the patient will be evaluated for 4 weeks to assess for toxicity. If no toxicity, then the will go on and get MRI of the brain every two months to assess for response up to 12 months. After this, the subject is done with the "experimental" aspects of the protocol. This is a Phase I trial that is designed to test the safety of the single dose intraarterial delivery of Avastin and Mannitol,.
Current Standard of Care: Surgery or radiosurgery: IV Avastin
Experimental portion of this proposal:
Day 0: Intraarterial Avastin single dose (starting at 2mg/kg and up to 10mg/kg) after Mannitol to open the blood brain barrier Day 28 (and every two months thereafter): MRI brain with contrast
Therefore the experimental aspects of this treatment plan will include:
1. Subjects will first be treated with Mannitol prior to chemotherapy infusion (Mannitol 25%; 3-10 mL/s for 30seconds) in order to disrupt the blood brain barrier. This technique has been used in several thousand patients in previous studies for the IA delivery of chemotherapy for malignant glioma.
2. To add a single intraarterial delivery (SIACI) of the Avastin with VS.
3. The dose escalation algorithm is as follows: We will use a single intracranial superselective intraarterial infusion of Avastin, starting at a dose of 2mg/kg in the first three patients. Assuming no dose limiting toxicity during the first 28 days after IA infusion, an MRI of the brain will be performed. The doses will be escalated to 4,6,8 and finally 10mg/kg in this Phase I trial.
Inclusion criteria Include: Males or females, >=18 years of age, with documented Radiologic or histologic diagnosis of VS
Both hematologic and non-hematologic toxicity will be determined and scored according to the NCI Common Toxicity Criteria (version 3.0). Monitoring will be conducted by post procedure history, neurological and physical examinations together with serial blood counts, prothrombin time (PT), partial thromboplastin time (PTT) and chemistries.
Response will be evaluated after 4 weeks via a MRI with the injection of contrast. The following will be evaluated every cycle, and then during follow-up: neurological examination, physical examination, performance status, laboratory parameters and review of adverse reactions. Contrast enhanced MRI (MRI with gadolinium is the preferable imaging study. The following subjects will be taken off protocol: those with progressive disease; those who experience dose-limiting toxicity (DLT). Follow-up will continue until disease progression or death. Survival will be measured from the time of the first dose of IA Avastin® (given at the start of each treatment cycle).
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Weill Cornell Medical College- NewYork Presbyteryan Hospital
Not yet recruiting
Weill Medical College of Cornell University
Published on BioPortfolio: 2014-08-27T03:15:19-0400
Surgical removal of vestibular schwannoma causes acute vestibular symptoms, including postoperative vertigo and oscilopsia due to nystagmus. In general, the dominant symptom postoperativel...
Previous studies have shown that vertigo is the symptoms that mostly affect quality of life in patients with vestibular schwannoma. There is still limited knowledge as to why some patients...
Response Prediction after Gamma Knife Surgery (GKS) in Patients with Vestibular Schwannoma using Dynamic Contrast-Enhanced (DCE) MR Imaging
This is a phase II prospective, randomized, double-blind, longitudinal study evaluating whether the administration of aspirin can delay or slow tumor growth and maintain or improve hearing...
Our hypothesis is that this study design, in which bevacizumab is added to one of six single agent chemotherapies with proven activity in metastatic breast cancer, will result in regressio...
There is a rare type of vestibular schwannoma, scarcely discussed in the literature, known as a hypervascular vestibular schwannoma (HVS).
To evaluate post-surgical postural stability when treating patients with remaining vestibular function with intratympanic gentamicin (PREHAB) prior to schwannoma surgery.
Vestibular schwannoma (VS) is a benign tumor that develops in the internal auditory canal and the cerebellopontine angle, potentially diminishing hearing or balance. Most VS tumors arise from one of ...
Resection of a vestibular schwannoma may result in facial paralyiss and hearing loss on the side of tumor. Authors have encountered a young female of neurofibromatosis type 2, who developed contralate...
Grade IV vestibular schwannoma (Koos classification) is generally considered to be an indication for microsurgical resection or combined radiosurgery-microsurgery. However, the place of Gamma knife st...
A benign SCHWANNOMA of the eighth cranial nerve (VESTIBULOCOCHLEAR NERVE), mostly arising from the vestibular branch (VESTIBULAR NERVE) during the fifth or sixth decade of life. Clinical manifestations include HEARING LOSS; HEADACHE; VERTIGO; TINNITUS; and FACIAL PAIN. Bilateral acoustic neuromas are associated with NEUROFIBROMATOSIS 2. (From Adams et al., Principles of Neurology, 6th ed, p673)
The vestibular part of the 8th cranial nerve (VESTIBULOCOCHLEAR NERVE). The vestibular nerve fibers arise from neurons of Scarpa's ganglion and project peripherally to vestibular hair cells and centrally to the VESTIBULAR NUCLEI of the BRAIN STEM. These fibers mediate the sense of balance and head position.
Vestibular nucleus lying immediately superior to the inferior vestibular nucleus and composed of large multipolar nerve cells. Its upper end becomes continuous with the superior vestibular nucleus. (From Dorland, 28th ed)
Pathological processes of the VESTIBULAR LABYRINTH which contains part of the balancing apparatus. Patients with vestibular diseases show instability and are at risk of frequent falls.
The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (COCHLEAR NERVE) which is concerned with hearing and a vestibular part (VESTIBULAR NERVE) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the SPIRAL GANGLION and project to the cochlear nuclei (COCHLEAR NUCLEUS). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the VESTIBULAR NUCLEI.
Hearing, auditory perception, or audition is the ability to perceive sound by detecting vibrations, changes in the pressure of the surrounding medium through time, through an organ such as the ear. Sound may be heard through solid, liquid, or gaseous mat...
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase 'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...