Flavopiridol and Docetaxel in Treating Patients With Advanced Solid Tumors

Phase I Study Of Flavopiridol And Docetaxel (Taxotere) In Patients With Advanced Cancers

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining flavopiridol and docetaxel in treating patients who have advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: docetaxel; Drug: alvocidib

Detailed Description

OBJECTIVES:

• Determine the dose-limiting toxic effects and maximum tolerated dose of flavopiridol and docetaxel in patients with advanced solid tumors.
• Determine the objective response rate and duration of response in patients treated with this regimen.
• Determine the pharmacokinetics of these drugs in this patient population.

OUTLINE: This is a dose-escalation study.

Patients receive docetaxel IV over 60 minutes on day 1 and flavopiridol IV continuously over 24 hours on day 2. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of docetaxel and flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study within 9-11 months.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute

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

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic or unresectable solid tumor

  • No standard relatively effective curative or palliative measures exist

• Measurable disease in at least 1 dimension

  • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• No known clinically active and uncontrolled brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2
• Karnofsky 60-100%

Life expectancy:

• More than 12 weeks

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin normal
• ALT/AST no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN

Renal:

• Creatinine normal

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• No prior allergic reactions to compounds of similar chemical or biologic composition to flavopiridol or docetaxel
• No other uncontrolled concurrent illness that would preclude study participation
• No ongoing or active infection
• No psychiatric illness or social situations that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent immunotherapy

Chemotherapy:

• At least 6 months since prior taxane therapy
• At least 4 weeks since other prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy except contraceptives, appetite stimulants, or replacement steroids

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Barbara Ann Karmanos Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Philip A. Philip, MD, PhD, FRCP, Barbara Ann Karmanos Cancer Institute

Publications and helpful links

General Publications

• El-Rayes BF, Gadgeel S, Parchment R, Lorusso P, Philip PA. A phase I study of flavopiridol and docetaxel. Invest New Drugs. 2006 Jul;24(4):305-10. doi: 10.1007/s10637-005-4343-5.
• Patel B, El-Rayes BF, Gadgeel SM, et al.: A phase I study of flavopiridol and docetaxel. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-932, 2003.

Study record dates

Study Major Dates

• Study Start: March 1, 2001
• Primary Completion (Actual): February 1, 2003
• Study Completion (Actual): December 1, 2005

Study Registration Dates

• First Submitted: May 6, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): April 5, 2013
• Last Update Submitted That Met QC Criteria: April 3, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: 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: CDR0000068605; P30CA022453 (U.S. NIH Grant/Contract); WSU-C-2197; NCI-1610