Threshold Pharmaceuticals, Inc. announced that results from its ongoing pivotal phase 3 trial of glufosfamide for the second-line treatment of pancreatic cancer will not be available until 2007. The company continues to expect top line results from a phase 2 trial of glufosfamide in combination with gemcitabine for first-line treatment of pancreatic cancer by the end of this year. Additionally, the company expects to have clinical trial sites open and patient screening underway for two additional phase 2 trials of glufosfamide in patients with ovarian cancer and patients with small cell lung cancer by the end of this year.
The phase 3 clinical trial results are based upon an event driven analysis that will be performed following notification of the 258th patient death in the trial. That event had previously been projected to occur in late November or early December, but the company, based upon a recently completed survival sweep, now expects this event to be reported in January 2007. Data analysis will occur within 4-6 weeks thereafter and the results then reported. The survival sweep consisted of a thorough outreach effort to all the clinical sites participating in the trial in order to get a current count of the survivors who remain in the clinical trial.
"In an event-driven analysis such as this, projecting the timing of the study completion is an inexact science. It is dependent on individual survival times of all patients in the trial as well as other prognostic factors such as performance status and extent of disease," said Barry Selick, Ph.D., Threshold's chief executive officer. "We have not, at this time, reached the 258th death but we are working towards being able to complete our analysis of the data and report results as quickly as possible following that event."
The phase 3 trial will evaluate approximately 300 previously-treated patients with metastatic pancreatic cancer who receive glufosfamide (4500mg/m2) once every 3 weeks or best supportive care (BSC). Best supportive care includes all medical or surgical interventions that a pancreatic cancer patient should receive to palliate the cancer but excludes treatment with systemic therapies intended to kill the cancer cells. The primary endpoint of this trial is overall survival as measured by time from randomization to death. The timing of the final analysis is therefore event-driven and will be conducted after the 258th death has occurred. In addition, the trial will investigate the potential efficacy of glufosfamide as determined by response rate, duration of response and progression-free survival, pain score, as well as safety. The company remains blinded to the individual patient data and is not aware of the number of deaths in each patient group (glufosfamide vs. BSC). As a result, the delay announced should not be interpreted as any one group living longer than the other.
The phase 3 trial is being conducted under a Special Protocol Assessment (SPA). In 2004, the FDA (Food and Drug Administration) granted fast track status to this program which provides for expedited regulatory review for new drugs that demonstrate the potential to address unmet medical needs for the treatment of serious or life-threatening conditions. In September 2006, the company received orphan drug designation from the FDA.
The ongoing phase 2 trial will evaluate up to 28 previously-untreated patients with locally advanced and/or metastatic pancreatic cancer who receive the standard dose of gemcitabine (1000mg/m2) weekly for 3 of every 4 weeks plus glufosfamide (4500mg/m2) administered once every 4 weeks. In addition to safety, the trial will investigate the efficacy of glufosfamide in combination with gemcitabine as determined by response rate, duration of response, progression-free survival, overall survival, six- and twelve-month survival and change in serum tumour marker levels.
The American Cancer Society estimates that 33,730 patients will be diagnosed with pancreatic cancer in the US in 2006, and approximately 32,300 patients will die from the disease. Only 15-20 per cent of newly diagnosed patients are eligible for surgery, which is typically followed by radiation and chemotherapy. Patients with inoperable pancreatic cancer are treated with radiation and chemotherapy, or in the case of advanced disease, chemotherapy alone as the advantages of radiation are reduced.
Threshold is a biotechnology company focused on the discovery and development of small molecule therapeutics for the potential treatment of cancer. By selectively targeting abnormally proliferating tumour cells, the company's drug candidates are designed to be potentially more effective and less toxic to healthy tissues than conventional treatments.