Combination Chemotherapy in Treating Patients With Advanced Solid Tumors

Single Center Open-Label Non-Comparative Phase I Dose Finding Study Of Weekly Flavopiridol In Combination With Weekly Docetaxel In Patients With Advanced Solid Tumors

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 with 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 maximum tolerated dose of flavopiridol when administered in combination with 2 different doses of docetaxel in patients with advanced solid tumors.
• Determine the clinical pharmacokinetics of this regimen in these patients.
• Determine, preliminarily, the therapeutic activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of flavopiridol.

Patients receive docetaxel IV over 30 minutes followed at least 4 hours later by flavopiridol IV over 1 hour on days 1, 8, and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Separate MTDs of flavopiridol are determined when flavopiridol is combined with 2 different doses of docetaxel. A total of 10 patients are treated at each flavopiridol MTD.

Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 6-56 patients will be accrued for this study.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • 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

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced solid tumor that is refractory to standard therapy or for which no standard therapy exists
• Measurable or evaluable disease
• No symptomatic or untreated CNS metastases or primary CNS neoplasm

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,500/mm3
• Absolute neutrophil count at least 1,500/mm3
• Platelet count at least 100,000/mm3
• Hemoglobin at least 8 g/dL

Hepatic

• Bilirubin no greater than upper limit of normal (ULN)
• SGOT/SGPT no greater than 2.5 times ULN if alkaline phosphatase no greater than ULN OR
• Alkaline phosphatase no greater than 2.5 times ULN if SGOT/SGPT no greater than ULN

Renal

• Creatinine no greater than 1.5 mg/dL

Cardiovascular

• No history of cardiac arrhythmias
• No congestive heart failure
• No myocardial infarction within the past 6 months

Other

• No concurrent serious or uncontrolled infection
• No diabetes not adequately controlled with medication
• No peripheral neuropathy greater than grade 1
• No known allergy to docetaxel or other medications formulated in Polysorbate 80
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 4 weeks since prior immunotherapy

Chemotherapy

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• Prior taxanes allowed
• No prior flavopiridol

Endocrine therapy

• At least 4 weeks since prior hormonal therapy

Radiotherapy

• At least 4 weeks since prior radiotherapy

Surgery

• Not specified

Other

• Recovered from prior therapy
• No prior enrollment in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2002
• Primary Completion (Actual): January 1, 2006
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: September 6, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): May 30, 2013
• Last Update Submitted That Met QC Criteria: May 29, 2013
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: 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: AVENTIS-HMR1275A/1501; MSKCC-02034; NCI-G02-2106; CDR0000256563 (Registry Identifier: PDQ (Physician Data Query))