Pancreatic Cancer - Phase I/IIa Clinical Trial of BC-819

Pancreatic Cancer - A Background

Pancreatic cancer is one of the most aggressive and devastating human malignancies. That the number of estimated pancreatic cases is almost identical to the number of pancreatic cancer related deaths illustrates its aggressiveness. Pancreatic cancer ranks as the fifth leading cause of cancer-related deaths in Western countries. It is more common in smokers than in nonsmokers and in males than in females, and it appears to be linked to a Western diet.

The majority of patients with pancreatic cancer present metastatic disease at the time of diagnosis. Pancreatic cancer metastasizes locally and regionally, to the lymph nodes, liver, lung, peritoneal cavity and adrenal gland. Surgery offers the only possibility of cure, but this is possible in only a small number of patients. Even when resection is possible, median survival times of 13-25 months and five-year survival rates of 10-20% have been reported. Prognosis is poor because of a high rate of local recurrence and metastasis, despite resection. A certain number of patients have carcinoma of the pancreas with an inoperable but non-metastasized tumor. In these patients, the tumor locally involves the mesenteric vessels, the superior mesenteric artery and vein, but usually the superior mesenteric vein or the portal vein to the extent that resection is impossible.

Medical Center Statistics

BioCancell's clinical partners report that 10-20% of patients presenting with pancreatic cancer have resectable tumors and will undergo surgical resection as the first option for treatment. Between 50 and 60% present with locally advanced unresectable disease that meets the inclusion criteria of BioCancell's Phase I/IIa pancreatic cancer clinical trial. The remaining 30-40% have metastatic disease. For those with locally advanced pancreatic cancer, a typical standard of care is combination chemoradiation, with the percentage of resection after neoadjuvant therapy around 5% or less. Thus, a new treatment that is well tolerated and can improve the percentage of patients whose tumor can be resected would offer a significant clinical benefit to patients with pancreatic cancer.

Phase I/IIa Clinical Trial Treatment Plan

The treatment plan for patients with locally advanced, unresectable pancreatic cancer is down-staging the tumor by shrinking its volume to the extent that vascular involvement is lessened and resection becomes possible. Recently, many investigators have reported the utility of chemotherapy using gemcitabine. In early studies with gemcitabine, patients experienced an improvement in disease-related symptoms, however, the median survival time (5.65 months) and the 12-month survival rate (18%) for gemcitabine-treated patients is disappointing. The combination of gemcitabine and irradiation caused both acute and late toxicity of the gastrointestinal tract.

Trial Objectives

The trial is designed primarily to assess the safety, tolerability and preliminary efficacy of the BC-819 plasmid administered intratumorally in patients with unresectable, locally advanced pancreatic cancer.

Trial Design

The selective initiation of toxin expression results in selective tumor cell destruction via inhibition of protein synthesis in the tumor cell, enabling highly targeted cancer treatment.

After obtaining informed consent, patients will be screened over a period of up to four weeks. If eligible, each patient will receive two weeks of twice weekly intratumoral BC-819, using a CT-guided percutaneous approach (PTA) or endoscopic ultrasound (EUS). The sites injected will be rotated over the two weeks of treatment such that a new site is injected at each treatment to the extent possible. Adverse events (AEs) and concomitant medication use will be assessed at each visit. Blood chemistries, hematology, coagulation indices, and urinalysis will be assessed after each treatment and at the tumor response assessment. Patients will be treated in the outpatient setting on the day of each BC-819 administration procedure and will remain in the hospital for an appropriate period of time after treatment for safety assessments.

Patients will be assessed during the fourth week of treatment for tumor response and possible tumor resection during the following weeks. Patients who have a tumor response (complete response, partial response, or stable disease) or who have their tumor resected will be followed up for tumor recurrence for one year after the start of treatment.

Inclusion/Exclusion Criteria

To be eligible to participate in this study, patients must meet a number of inclusion/exclusion criteria.

Enrollment information

This trial is no longer recruiting patients.