Paclitaxel and Bryostatin 1 in Treating Patients With Advanced Pancreatic Cancer

PRIMARY OBJECTIVES:

I. To determine the response rates to weekly, sequential paclitaxel/ bryostatin-1 in patients with unresectable and metastatic pancreatic cancer.

II. To determine the toxicity of therapy. III. To determine patient survival after therapy. IV. To determine Bryostatin-1 pharmacokinetics.

OUTLINE: This is an open-label, multicenter study.

Patients receive paclitaxel IV over 1 hour on day 1 followed by bryostatin 1 IV over 1 hour on day 2 of weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Inclusion criteria

• Histologic proof of adenocarcinoma of the pancreas that is locally advanced and considered surgically not resectable or metastatic
• Patients with or without prior treatment are eligible for treatment on protocol; prior treatment may have included one treatment course of chemo/RT and/ or one course of chemotherapy, but not two prior courses of chemotherapy;
• Measurable disease
• ECOG performance status of 0-1
• Ability to sign an informed consent form indicating awareness of the investigational nature of this study, in keeping with the policies of the hospital
• Patients may not be receiving any other concurrent chemotherapy, immunotherapy, or radiotherapy; the most recent treatment for pancreatic cancer, within the limitations of allowed prior therapy must be 28 days or longer prior to enrollment on study
• Absolute granulocytes > 1,500/mm^3
• Platelets > 150,000/mm^3
• Serum bilirubin < 1.5 mg/dl
• Serum creatinine < 1.5 mg/dl

Exclusion criteria

• Presence of any ongoing toxic effect from prior treatment
• Brain metastases
• History of active angina or myocardial infarction within 6 months; history of significant ventricular arrhythmia requiring medication with antiarrhythmics; well controlled atrial fibrillation on standard management will be permitted
• Pregnant or lactating women
• Pre-existing neurotoxicity that is graded 3+ or greater
• Serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy
• Psychiatric disorders rendering patients incapable of complying with the requirements of the protocol
• HIV infection
• Any other medical condition or reason that, in the investigator's opinion, makes the patient unsuitable to participate in a clinical trial (for example a history of prior poor compliance with treatment)