Docetaxel and Flavopiridol in Treating Patients With Refractory Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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An Open-Label, Non-Randomized Phase II Study of Alvocidib (Flavopiridol) in Combination With Docetaxel in Refractory, Metastatic Pancreatic Cancer (NCI #6366)

Conditions
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Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage IV Pancreatic Cancer

Intervention / Treatment
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* Drug: alvocidib
* Drug: docetaxel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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 (docetaxel and alvocidib)<br>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. | Drug: alvocidib<br>* Given IV<br>* Other names: L-868275;Drug: docetaxel<br>* Given IV<br>* Other names: TXT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate as Measured by RECIST Criteria | Objective response rate as measured by RECIST criteria | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Will be computed using Kaplan-Meier methods. | Between the start of treatment until the criteria for progression are met, assessed up to 2 years | 
| Overall Survival | Will be computed using Kaplan-Meier methods. | Between the start of treatment until patient death, assessed up to 2 years |