Clinical trial NCT00331682: Docetaxel and Flavopiridol in Treating Patients With Refractory Metastatic Pancreatic Cancer
Official title: An Open-Label, Non-Randomized Phase II Study of Alvocidib (Flavopiridol) in Combination With Docetaxel in Refractory, Metastatic Pancreatic Cancer (NCI #6366)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage IV Pancreatic Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-05-31
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate as Measured by RECIST Criteria
timeFrame: Up to 2 years
Secondary outcomes:
measure: Time to Progression
timeFrame: Between the start of treatment until the criteria for progression are met, assessed up to 2 years
measure: Overall Survival
timeFrame: Between the start of treatment until patient death, assessed up to 2 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Eileen O'Reilly
role: PRINCIPAL_INVESTIGATOR
References: