Clinical Trial of Perifosine and Temsirolimus in Recurrent Malignant Gliomas with Molecular Correlates of Efficacy
Led by Andrew B. Lassman, MD at Memorial Sloan-Kettering Cancer Center
The Lynn Kohlman Memorial Grant
Approximately 70% of glioblastomas exhibit abnormal activity with respect to a certain chemical, called AKT. AKT activates another chemical, which increases the likelihood of tumor growth, invasion, and resistance to treatments usually employed to treat gliobastomas, such as radiation therapy.
Perifosine is a new drug that inhibits AKT, and has shown benefit in patients with other types of cancer. A trial was conducted by these investigators to evaluate the ability to treat recurrent glioblastoma patients, and although not toxic, it was also not effective.
These investigators believe that another drug, temsirolimus and perifosine together may have benefit in treating patients with glioblastoma.
Laboratory trials have shown promise for this combination in mice.
The refractory nature of brain tumors challenges neuro-oncologists to refine current treatment approaches and test new therapies. Glioblastomas (GBM) are the most common malignant brain tumor in adults and are one of the most resistant of all cancers to treatment. Memorial Sloan-Kettering Cancer Center’s Department of Neurology has been on the forefront of research in this area.
With funding from Voices Against Brain Cancer, Dr. Andrew Lassman has been working with pathologists, geneticists, radiologists, neurosurgeons and statisticians on a study to evaluate the safety and effectiveness of a novel combination of medications.
Brain tumor molecular biology research has revealed that AKT, a protein, provides a key signal instructing tumor cells to proliferate, invade normal brain tissue and resist traditional therapies. Two drugs, perifosine and temsirolimus, have been shown to work synergistically to kill brain tumor cells in mice. Dr. Lassman is conducting a clinical trial utilizing this combination therapy. In collaboration with laboratory investigators, brain tumor tissue will be examined to determine why some patients respond better than others and how individualized treatment regimens can be devised.
The clinical trial formally opened to accrual on January 28, 2010. To date, five patients have been treated without unacceptable side effects. Accrual to the study continues and tissue analysis is ongoing.
During the next year the goals of this project are to:
- Complete the phase I portion and determine the maximum dosages of both drugs that can be administered safely.
- Complete the phase II portion and assess the effect of the treatment on patient survival.
- Explore the association of pre-treatment molecular phenotype with response to treatment and molecular effects during treatment.
Click here for a full list of research grants funded by Voices Against Brain Cancer.