Docetaxel and Flavopiridol in Treating Patients With Refractory Metastatic Pancreatic Cancer

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.

Study Overview

• Status: Completed
• Conditions: Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage IV Pancreatic Cancer
• Intervention / Treatment: Drug: alvocidib; Drug: docetaxel

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (docetaxel and 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.	Drug: alvocidib; Given IV; Other Names: FLAVO; flavopiridol; HMR 1275; L-868275; Drug: docetaxel; Given IV; Other Names: Taxotere; RP 56976; TXT

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Eileen O'Reilly, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: May 30, 2006
• First Submitted That Met QC Criteria: May 30, 2006
• First Posted (Estimate): May 31, 2006

Study Record Updates

• Last Update Posted (Estimate): May 28, 2014
• Last Update Submitted That Met QC Criteria: May 12, 2014
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Docetaxel; Alvocidib
• Other Study ID Numbers: NCI-2012-01471; 05-136; R01CA067819 (U.S. NIH Grant/Contract); MSKCC-05136; NCI-6366; CDR0000472413