Pharmacyclics Completes Patient Enrollment in Pivotal Xcytrin Phase III Trial For Brain Metastases
Company Plans to Announce Top-Line Results by End of 2001
SUNNYVALE, Calif., March 14 /PRNewswire/ -- Pharmacyclics, Inc. (Nasdaq: PCYC - news), announced today that patient enrollment has been completed in its pivotal international randomized controlled Phase III clinical trial of Xcytrin® (motexafin gadolinium) Injection for the treatment of brain metastases, i.e., cancer that has spread to the brain from another part of the body.
This trial was conducted at more than 60 leading cancer centers in the United States, Canada and Europe and enrolled 428 patients. It is designed to compare the safety and efficacy of standard whole brain radiation to standard whole brain radiation plus Xcytrin. Improvement in survival and time to neurologic progression are the co-primary efficacy endpoints of this trial, and the U.S. Food and Drug Administration has indicated that either one or both could serve as the basis of approval.
``Thanks to the dedicated efforts and commitment of our clinical investigators and their staffs, this is the most comprehensive and fastest enrolling clinical trial in brain metastases ever performed,'' said Markus Renschler, M.D., senior director of clinical development for Pharmacyclics. ``According to the protocol design, patients will now be followed for an additional six months. During that time, we will collect and analyze the co-primary endpoint data, and should be able to announce a top-line analysis of results by the end of this year.''
Xcytrin is the first of a new class of drugs called texaphyrins. Xcytrin selectively accumulates in cancer cells and disrupts cellular metabolism by a unique mechanism of action. By interfering with the flow of energy in cancer cells, Xcytrin makes the tumor more responsive to the effects of radiation and chemotherapy without increasing damage to normal tissue.
``Clinical data reported to date indicate that Xcytrin appears to improve local tumor control in the brain, with few patients experiencing tumor progression, neurologic deterioration, or death due to tumor progression,'' said Minesh Mehta, M.D., associate professor and interim chair, Department of Human Oncology, University of Wisconsin Medical School, Madison, and co-chairman of the Phase III trial.
Xcytrin has been well tolerated, and the most commonly occurring side effects have been nausea and reversible liver enzyme abnormalities. The trial's independent Data Safety Monitoring Board (DSMB) met earlier this year to perform a formal interim analysis of the data on the initial 341 randomized patients. The DSMB commended the trial's design and data management procedures and had no concerns regarding the drug's safety, recommending that the trial be continued without any design changes.
This is the first trial of its kind to comprehensively and objectively evaluate brain function using neurological signs and symptoms, a battery of standard neurocognitive tests, and regularly scheduled, standardized magnetic resonance imaging of the brain. Neurologic progression is determined by an independent Events Review Committee that is blinded to the treatment assignment.
``In addition to definitively determining whether Xcytrin improves radiation therapy for this increasingly common condition, this trial also establishes a new standard for clinical trials involving the treatment of all types of brain tumors,'' said Walter Curran, M.D., chairman of the Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, the other co-chairman of the Phase III trial. ``Xcytrin has potential not only in treating brain metastases, but also in becoming an important new therapy for the treatment of many types of cancer.''
Studies with Xcytrin in other types of cancer are also underway. Under a cooperative research and development agreement with Pharmacyclics, the National Cancer Institute is conducting clinical trials of Xcytrin for the treatment of primary brain tumors, non-small-cell lung cancer, childhood gliomas (life-threatening brain tumors in children), and pancreatic cancer. Several other trials, including a Phase II trial in primary brain tumors, are in the planning stages and will be initiated throughout the year.
``Investigators will report clinical results for Xcytrin treatment of primary brain tumors and childhood gliomas at the American Society of Clinical Oncology (ASCO) annual meeting in May,'' added Dr. Renschler. ``There are several other presentations at ASCO describing Xcytrin's mechanism of action, tumor localization and pharmacokinetics.''
Brain Metastases: An Increasing Clinical Problem
Brain metastasis is one of the most common conditions treated with radiation therapy. There are about 170,000 cases per year in the United States and the incidence is increasing. The most common causes of brain metastases are lung and breast cancer. Brain metastases occur when cancer cells spread to the brain and grow, causing major neurologic complications and, in many cases, death. Patients with brain metastases usually suffer serious deterioration of neurocognitive function, such as loss of short-term memory, compromised verbal skills and fine motor coordination, and reduction in cognitive performance. Most patients with brain metastases have multiple lesions and are not candidates for surgical resection or radiosurgery. The goal of whole brain radiation therapy is to reverse or prevent neurological deterioration and prevent death due to tumor progression in the brain. No new treatments have been approved to enhance the efficacy of whole brain radiation... |
