Paclitaxel and Bryostatin 1 in Treating Patients With Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase II Study of Sequential Paclitaxel and Bryostatin-1 for Patients With Advanced Pancreatic Cancer

Conditions
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Acinar Cell Adenocarcinoma of the Pancreas, Duct Cell Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer

Intervention / Treatment
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* Drug: paclitaxel
* Drug: bryostatin 1


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (paclitaxel, bryostatin 1)<br>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. | Drug: paclitaxel<br>* Given IV<br>* Other names: Taxol;Drug: bryostatin 1<br>* Given IV<br>* Other names: Bryostatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate of at Least 30% | Number of participants with a Response rate of at least 30%. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). | Up to 8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events |  | Up to 8 years | 
| Overall Survival | Computed using the Kaplan-Meier estimator. | Up to 8 years |