An Open-Label, Non-Randomized Phase II Study of Alvocidib (Flavopiridol) in Combination With Docetaxel in Refractory, Metastatic Pancreatic Cancer (NCI #6366)
An Open-Label, Non-Randomized Phase II Study of Alvocidib (Flavopiridol) in Combination With Docetaxel in Refractory, Metastatic Pancreatic Cancer (NCI #6366)
Drugs used in chemotherapy, such as docetaxel and flavopiridol, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Flavopiridol may also help docetaxel work better by making tumor cells more sensitive to the drug. This phase II trial is studying how well giving docetaxel followed by flavopiridol works 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
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
Documented progression with measurable metastatic disease including any 1 of the following criteria:
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
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
No concurrent combination antiretroviral therapy for HIV-positive patients