Direct Therapeutics Inc has received approval to begin the first European trial of DTI-015, a novel chemotherapy designed for direct injection to brain tumors. The single-center study will be conducted in England at the Walton Centre for Neurology and Neurosurgery under the direction of physicians from the University of Liverpool. It will examine the clinical safety and efficacy of DTI-015 administered at time of tumor biopsy to patients with newly diagnosed primary anaplastic astrocytoma (grade III brain tumor) or glioblastoma multiforme (grade IV brain tumor) and will also examine the effects of DTI-015 on tumor vasculature.

The company received approval to begin the trial from the United Kingdom's Medicines Control Agency, which expressed no objections to the company's Clinical Trial Exemption application. In addition to initiating study of DTI-015 in a new indication, the trial also paves the way for DTI-015 to be considered for marketing approval throughout the European Union, where it has already received Orphan Drug designation for the treatment of gliomas.

After treatment with DTI-015, patients enrolled in the study will go on to receive standard therapies for the treatment of their brain tumors as directed by their physician. In the United Kingdom, these treatments primarily include radiation therapy and intravenous chemotherapies, and, less commonly, surgery to remove the tumor or reduce its mass.

Two earlier Phase I/II studies, both conducted in the United States, established the Maximum Tolerated Dose of DTI-015 and demonstrated its safety and activity in patients with recurrent inoperable high-grade gliomas. A single-center, physician-sponsored Phase I/II trial, conducted at the University of Texas M.D. Anderson Cancer Center (Houston) in patients with recurrent inoperable high-grade gliomas, demonstrated a doubling of median overall survival time -- from the expected 25 weeks to 55 weeks - for patients with recurrent inoperable glioblastoma multiforme who were treated at or below Maximum Tolerated Dose. Direct Therapeutics recently concluded the treatment portion of its multi-center, company-sponsored, Phase I/II study of DTI-015 in patients with recurrent inoperable glioblastoma multiforme.

Patients in both the Direct Therapeutics and M.D. Anderson studies had recurrent tumors that were deemed inoperable. All had been heavily treated for their disease before entering the study. Many had undergone two or more surgical procedures, all received radiation therapy, and most received intravenous chemotherapy with nitrosoureas.

DTI-015 contains the active ingredient carmustine (1-3 bis [2-chloroethyl]-1-nitrosourea) in an ethanol solvent base. Carmustine is commonly used to treat brain tumors by intravenous injection, a method that limits the dose because it exposes the whole body to the serious toxicities of the drug. DTI-015, in contrast, is injected directly to brain tumors using standard image-guided stereotactic injection, a minimally invasive surgical procedure similar to that used for obtaining brain tumor biopsies. The ethanol solvent vehicle in DTI-015 transports the carmustine selectively throughout the tumor mass and into both the aqueous and lipid compartments of tumor cells. As a result, DTI-015 rapidly, thoroughly, and selectively saturates tumor tissue with high doses of carmustine not achievable by other means.

According to the American Cancer Society, there are 36,000 new cases of primary brain cancer diagnosed each year in the United States. Nearly all patients with glioblastoma multiforme and anaplastic astrocytoma die from the disease or its complications.