Background
Glioblastoma (GBM, WHO grade IV glioma) is the most common primary malignant brain tumor among adults.
Regardless of the treatment regimen, many patients relapse and are faced with limited treatment options. The aggressive infiltration of GBM throughout the brain typically limits the efficacy of repeat surgical resection, and tumor cells frequently acquire resistance to further cytotoxic therapy. Therefore, recurrent GBM does not respond well to repeat surgery, re-irradiation, and additional rounds of chemotherapy. At the same time, these interventions may moderately increase overall survival, but the prognosis for these patients remains exceptionally poor.
Given the persistent medical need for improved treatments, NeOnc began investigating a type of intervention, intranasal delivery of perillyl alcohol (POH, NEO100), for patients with recurrent GBM. Extensive preclinical studies provided strong evidence of POH’s natural anticancer potential. Though the exact mechanism of POH’s anticancer effect is unclear, it most likely results from the pleiotropic effects including cell cycle arrest, endoplasmic reticulum stress, and induction of apoptosis.
Protocol
In the two-year study conducted at the Cleveland Clinic at the University of Washington/Seattle, the University of Wisconsin, and the University of Southern California study, 12 patients were enrolled and divided into four cohorts. Candidates for the clinical study needed to meet the following criteria:
- Were 18 years of age or older.
- Had a confirmed progression or recurrent grade IV Glioma.
- Had been on a stable dose of steroids for at least five days.
- Had failed previous radiation and Temozolomide treatment.
- Had an ECOG1 performance status of 0-2, or;
- Had Karnofsky’s 2 performance status ≥60.
- Had an expected survival rate of at least 3 months.
- Showed a baseline MRI with gadolinium within two weeks of trial.
- Had seizures which were being controlled on a stable dose of anti-epileptics for two weeks prior to
enrollment.
