Docetaxel and Flavopiridol in Treating Patients With Refractory Metastatic Pancreatic Cancer

PRIMARY OBJECTIVES:

I. Determine the response rate in patients with refractory, metastatic pancreatic cancer treated with weekly, sequential docetaxel and flavopiridol.

SECONDARY OBJECTIVES:

I. Determine the time to progression and overall survival of patients treated with this regimen.

II. Assess the toxicity of this regimen.

OUTLINE: This is a non-randomized, open-label, prospective study.

Patients receive docetaxel IV over 30 minutes followed 4-6 hours later by flavopiridol IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Inclusion criteria

• Histologically or cytologically confirmed adenocarcinoma of the pancreas

• Evidence of metastatic disease
• Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20mm with conventional techniques or as ≥ 10 mm with spiral CT scan

• The primary site is not a measurable lesion
• Documented progression with measurable metastatic disease including any 1 of the following criteria:

• Receiving adjuvant therapy for resected disease
• Receiving therapy for locally advanced disease
• Within 3 months of completing adjuvant therapy or therapy for locally advanced disease
• On 1 prior regimen in the metastatic setting
• No documented brain metastases
• Karnofsky performance status (PS) 80-100% OR ECOG PS 0-1
• WBC ≥ 2,500/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT < 2.5 times ULN
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Alkaline phosphatase ≤ 5 times ULN
• No history of allergic reactions to compounds of similar chemical orbiological composition to flavopiridol
• No known allergy to docetaxel or medications formulated in polysorbate 80 (Tween 80)
• No uncontrolled diabetes
• No uncontrolled intercurrent illness including, but not limited to any of the following:

• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia or myocardial infarction within the past 6 months

• Rate-controlled atrial fibrillation stable for ≥ 6 months allowed
• Psychiatric illness or social situations that would limit compliance with study requirements
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• No peripheral neuropathy > grade 1
• No immune deficiency
• Atl east 2 weeks since prior chemotherapy (6 weeks for nitrosoureas, carmustine, or mitomycin C) and recovered
• At least 2 weeks since prior targeted therapy (e.g., antiangiogenic therapy [e.g., bevacizumab] or epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor [e.g., erlotinib hydrochloride]) and recovered
• At least 4 weeks since prior radiation therapy
• No prior docetaxel or flavopiridol
• No other concurrent chemotherapy or investigational agents
• No other concurrent anticancer agents or therapies
• No concurrent commonly used vitamins, antioxidants, orherbal preparations or supplements

• Single-tablet multivitamin allowed
• No concurrent combination antiretroviral therapy for HIV-positive patients