Experimental Drug and New Delivery System in Multi-Center Phase III Clinical Trial Throughout North America, Europe, Israel
Sep 23, 2004
Physician-scientists at NewYork-Presbyterian Hospital/Weill Cornell Medical Center will join roughly 50 other medical centers around the world in studying whether an experimental drug delivered directly into the brain can extend the lives of people with Glioblastoma Multiforme (GBM), the most common and aggressive form of primary brain tumor.
Even after doctors surgically remove a tumor, cancerous cells inevitably remain in the area surrounding a tumor site. They are generally embedded in tissue and, especially in the case of GBM, tend to proliferate rapidly, leaving the patient with a high risk of recurrence.
In a trial known as the PRECISE Trial, an experimental drug called IL13-PE38QQR, and a delivery system known as "convection-enhanced delivery" (CED), will be tested to determine their effectiveness in treating these deadly cancerous cells. IL13-PE38QQR is made by combining a human protein (IL13) with the bacterial toxin protein, Pseudomonas Exotoxin (PE). Metaphorically, IL13 is the "glue" that binds the drug to cancer while PE is the "hammer" that destroys it.
PRECISE is a Phase III clinical trial, and at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, its principal investigator is Dr. Theodore Schwartz. "The initial results from Phase I and II studies of IL13-PE38QQR are extremely exciting and offer new hope to patients who may have run out of options," says Dr. Schwartz, Assistant Attending Neurological Surgeon at NewYork-Presbyterian/Weill Cornell, and Assistant Professor of Neurological Surgery at Weill Cornell Medical College.
"Trials such as this," notes Dr. Philip Stieg, Neurological Surgeon-in-Chief at NewYork-Presbyterian/Weill Cornell, and Chair and Professor of Neurological Surgery at Weill Cornell Medical College, "are a reason why academic medical centers are so important in developing new treatments. We have the ability here to combine research with clinical care and offer patients something that is perhaps their best hope."
A Multi-Staged Process
Treating a GBM tumor is conducted in several stages. In the first stage, Dr. Schwartz and his team surgically remove as much of the tumor as can be removed safely. Within a few days following surgery, the patient undergoes an MRI of the tumor site to help plan the placement of the CED catheters to introduce IL13-PE38QQR.
During a second operation, the surgical team passes catheters through the skull, either using the opening from the previous surgery or by creating small new holes in the skull. An image guidance system ensures that the catheters are in their correct position, and from here, convection-enhanced delivery takes place. With CED, a pump slowly pushes the drug through the catheters and into the area surrounding the surgical resection. It typically takes place over a four-day period, and during that time, a patient is able to walk about, although not engage in activities that are too rigorous. Treatment occurs in the hospital.
Convection-enhanced delivery is important because it allows a drug to bypass something called the "blood-brain barrier." In most parts of the body, the smallest blood vessels, called capillaries, are lined with endothelial tissue. Endothelial tissue has small spaces between each individual cell, allowing substances to move readily between the inside and the outside of the vessel. However, in the brain, the endothelial cells fit tightly together and prohibit most intravenous chemotherapy agents from reaching cancerous cells within the brain.
Following surgery, the patient undergoes routine follow-up MRI scans to ensure that cancer has not returned.
The PRECISE Trial
The PRECISE Trial is occurring at sites in North America, Europe, and Israel, and it will eventually enroll approximately 300 patients. Participants in the study will be assigned to one of two groups — two-thirds receiving IL13-PE38QQR and one-third receiving U.S. Food and Drug Administration-approved chemotherapeutic "wafers." Wafers are placed in the tumor cavity and slowly dissolve over a two- to three-week period, releasing chemotherapeutic drugs to the area. They are now the standard treatment for GBM brain tumors, and although wafers are effective in extending survival by a few months, tumors often still recur. It is believed that IL13-PE38QQR, which preferentially binds to cancerous cells over healthy ones, will give patients a better chance at living longer and without the unwanted side effects of chemotherapy.
About GBM Brain Tumors
Glioblastoma Multiforme (GBM) is the most common and aggressive form of primary brain tumor and, in most cases, will occur in people between the ages of 40 and 60. The glioma family of tumors account for slightly less than half (44 percent) of all primary brain tumors, with GBM being the most common and aggressive. GBM is a highly malignant tumor that infiltrates the normal brain tissue surrounding the tumor. Most gliomas are known to re-grow close to the cavity left after the removal of the tumor, but the cancerous cells may also invade the membranes covering the brain or spread to other areas of the body via spinal fluid.
Most people live for less than one year after diagnosis of GBM and, on average, four to six months after the first recurrence or progression, due in large part to the very limited treatment options. People with GBM typically suffer from a varied degree of symptoms that could include headaches, nausea and vomiting, personality changes, seizures, vision loss, and slowing of cognitive function.
Current methods to destroy the remaining cancer cells with radiation or chemotherapy have resulted in a median survival rate after initial diagnosis of about nine to 12 months.
NeoPharm Inc., a company based in Lake Forest, Illinois, funds the PRECISE Trial and supplies the IL13-PE38QQR, which was developed in the Laboratory of Molecular Tumor Biology of the U.S. Food and Drug Administration.
For information on the PRECISE Trial at NewYork-Presbyterian Hospital/Weill Cornell Medical Center please contact:
Jennifer Serventi, R-PAC
Division of Neuro-Oncology
NewYork-Presbyterian Hospital/Weill Cornell Medical Center
Participants must be at least 18 years of age and have a diagnosis of first recurrence Glioblastoma Multiforme (GBM). The tumor must have recurred after surgical removal, radiation, and chemotherapy were used to treat the initial tumor.