Docetaxel and Flavopiridol in Treating Patients With Refractory Metastatic Pancreatic Cancer

• ClinicalTrials.gov Identifier: NCT00331682
• Recruitment Status: Completed
• First Posted: May 31, 2006
• Results First Posted: January 10, 2014
• Last Update Posted: May 28, 2014
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage IV Pancreatic Cancer	Drug: alvocidib; Drug: docetaxel	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: March 2006
• Actual Primary Completion Date: May 2008
• Actual Study Completion Date: May 2008

Arms and Interventions

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: RP 56976; Taxotere; TXT

Outcome Measures

Primary Outcome Measures :

1. Objective Response Rate as Measured by RECIST Criteria [ Time Frame: Up to 2 years ]
   Objective response rate as measured by RECIST criteria

Secondary Outcome Measures :

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

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, New York

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10065

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Eileen O'Reilly; Memorial Sloan Kettering Cancer Center

More Information

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00331682
• Other Study ID Numbers: NCI-2012-01471; 05-136; MSKCC-05136; NCI-6366; CDR0000472413; R01CA067819 ( U.S. NIH Grant/Contract )
• First Posted: May 31, 2006
• Results First Posted: January 10, 2014
• Last Update Posted: May 28, 2014
• Last Verified: November 2013

Additional relevant MeSH terms:

Adenocarcinoma; Pancreatic Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Docetaxel; Alvocidib; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Growth Inhibitors; Growth Substances; Physiological Effects of Drugs; Protein Kinase Inhibitors; Enzyme Inhibitors