Docetaxel and Flavopiridol in Treating Patients With Refractory Metastatic Pancreatic Cancer

Phase 2

Completed

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

Interventions: Drug: alvocidib
Drug: docetaxel

Registration Number: NCT00331682

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (docetaxel and alvocidib)	docetaxel	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.
Treatment (docetaxel and alvocidib)	alvocidib	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.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate as Measured by RECIST Criteria	Up to 2 years	Objective response rate as measured by RECIST criteria

Secondary Outcome Measures

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