Phase II trial to study the effectiveness of combining paclitaxel and bryostatin-1 in treating patients who have locally advanced unresectable or metastatic pancreatic cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Bryostatin-1 may help paclitaxel kill more cancer cells by making tumor cells more sensitive to the drug.

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)