Threshold Pharmaceuticals Inc. has initiated patient enrolment for a phase 2 clinical trial evaluating the efficacy and safety of glufosfamide in patients with previously treated, advanced, soft tissue sarcoma. Soft tissue sarcoma includes cancers of cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.

"The treatment of advanced, soft tissue sarcoma remains a major unmet medical need that disproportionately affects younger patients," said Lee Cranmer, MD, PhD, Arizona Cancer Centre, and a clinical investigator for the trial. "New agents are definitely needed. I am hopeful that glufosfamide may provide a new treatment option for these patients. I look forward to collaborating with this important exploratory trial."

Twenty-two patients with previously treated, advanced, soft tissue sarcoma are planned to enrol in the phase II, open-label, clinical trial at various sites in the United States. All patients are to receive 5000 mg/m^2 of glufosfamide every three weeks for up to six cycles.

The primary efficacy endpoint of the trial is objective response rate. The secondary endpoints of the trial include duration of response, progression- free survival, overall survival and various safety parameters. Tumour response will be evaluated at baseline and every six weeks using the Response Evaluation Criteria In Solid Tumours (RECIST). One exploratory objective of the trial is to evaluate the biological effects of glufosfamide on metabolic profile as determined by FDG-PET (fluorodeoxyglucose-positron emission tomography).

The role of this procedure is to detect metabolically active malignant lesions and to monitor their metabolic response to glufosfamide therapy. An additional exploratory objective of the trial is to correlate efficacy endpoints with expression of tumour-associated glucose transporter proteins.

Soft tissue sarcomas are treated with surgery, chemotherapy and radiation. Usually a combination of these modalities offers the best chance to treat the disease successfully. Doxorubicin and ifosfamide are the most commonly used chemotherapeutic agents in patients with advanced soft tissue sarcoma, but response rates are low and toxicity is significant. The American Cancer Society estimates that 9,220 people will be diagnosed with a soft tissue sarcoma in the United States in 2007, and approximately 3,560 people will die from these diseases.