RATIONALE: 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.

PURPOSE: 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.

Condition	Treatment or Intervention	Phase
stage II pancreatic cancer stage III pancreatic cancer recurrent pancreatic cancer adenocarcinoma of the pancreas stage IVA pancreatic cancer stage IVB pancreatic cancer	Drug: bryostatin 1  Drug: paclitaxel  Procedure: chemosensitization/potentiation  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the complete and partial response rates in patients with locally advanced unresectable or metastatic adenocarcinoma of the pancreas treated with sequential paclitaxel and bryostatin 1.
• Determine the survival of patients treated with this regimen.
• Determine the toxicity and pharmacokinetics of this regimen in these patients.

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.

PROJECTED ACCRUAL: A total of 18-35 patients will be accrued for this study within 1 year.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the pancreas
• Locally advanced and unresectable disease OR
• Metastatic disease
• At least 1 unidimensionally measurable lesion
• At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• Indicator lesion within field of prior irradiation must have evidence of disease progression
• No brain metastases

PATIENT CHARACTERISTICS: Age:

• Over 18

Performance status:

• ECOG 0-1 OR
• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute granulocyte count greater than 1,500/mm^3
• Platelet count greater than 150,000/mm^3

Hepatic:

• Bilirubin less than 1.5 mg/dL

Renal:

• Creatinine less than 1.5 mg/dL

Cardiovascular:

• No history of active angina
• No myocardial infarction within the past 6 months
• No history of significant ventricular arrhythmia requiring antiarrhythmics
• Well-controlled atrial fibrillation on standard management allowed

Other:

• No history of HIV disease
• No other active malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• Prior T1a or b prostate cancer (detected incidentally during transurethral resection of prostate [TURP] and comprising less than 5% of resected tissue) is allowed provided PSA normal since TURP
• No serious concurrent infection
• No concurrent uncontrolled nonmalignant medical illness (control must not preclude study participation)
• No psychiatric disorder that would preclude study participation
• No other medical condition that would preclude study participation
• No pre-existing neurotoxicity grade 3 or greater
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study participation

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Prior biologic therapy (e.g., trastuzumab [Herceptin], epidermal growth factor receptor antagonists, or ras inhibitors) allowed
• Prior adjuvant vaccine therapy allowed
• No prior biological response modifiers
• No concurrent immunotherapy

Chemotherapy:

• No more than 2 courses of prior standard cytotoxic chemotherapy for pancreatic cancer, including any of the following:
• One course of neoadjuvant, adjuvant, or definitive chemoradiotherapy
• One course of chemotherapy alone (e.g., gemcitabine or combination chemotherapy)
• One course of chemoradiotherapy followed by chemotherapy alone (e.g., gemcitabine)
• No prior taxanes (e.g., paclitaxel) for pancreatic cancer
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• See Chemotherapy
• Prior radiotherapy allowed
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• Recovered from prior therapy
• At least 4 weeks since other prior therapy for this disease

New York
      Albert Einstein Clinical Cancer Center, Bronx,  New York,  10467,  United States
      Mount Sinai Medical Center, NY, New York,  New York,  10029,  United States
      North Shore University Hospital, Manhasset,  New York,  11030,  United States
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States

Study chairs or principal investigators

Andreas Kaubisch, MD,  Study Chair,  Albert Einstein Cancer Research Center   

Study ID Numbers:  CDR0000069216; AECM-019224; NCI-5624
Record last reviewed:  December 2003
Last Updated:  October 13, 2004
Record first received:  March 8, 2002
ClinicalTrials.gov Identifier:  NCT00031694
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08