Flavopiridol and Irinotecan in Treating Patients With Advanced Solid Tumors

An Open-Labeled, Non-Randomized Phase I Study Of Flavopiridol Administered With Irinotecan (CPT-11) 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 irinotecan in treating patients who have locally advanced or metastatic solid tumors.

Study Overview

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

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of flavopiridol when combined with irinotecan in patients with advanced solid tumors.
• Determine the clinical pharmacokinetics of this regimen, as well as the plasma levels of the active metabolite SN-38 and metabolic product SN-38 glucuronide in these patients.
• Determine, in a preliminary manner, the therapeutic activity of this regimen in these patients.
• Determine the role of p21 relative to treatment response and apoptosis in these patients treated with this regimen.

OUTLINE: This is a dose-escalation, open-label, non-randomized study of flavopiridol.

Patients receive irinotecan IV over 30 minutes followed 7 hours later by flavopiridol IV over 1 hour on days 1, 8, 15, and 22. Treatment continues every 6 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity. During the first week of the second course, patients receive flavopiridol alone on day 1 and irinotecan alone on day 2.

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 2 or more of 6 patients in the initial cohort experience dose limiting toxicity during the first course of treatment. An additional 10 patients are treated at the MTD.

PROJECTED ACCRUAL: A total of 44-50 patients will be accrued for this study within 1 year.

• 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 proven locally advanced or metastatic solid tumor that is refractory to standard therapy or for which no standard therapy exists

• Eligible for treatment at the maximum tolerated dose only if disease accessible for tissue biopsy by Tru-Cut, CT guidance, or endoscopy

  • Pleural effusions or abdominal ascites do not constitute adequate tissue for biopsy
• No known CNS metastasis or primary CNS tumor

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT and SGPT no greater than 2.5 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No cardiac arrhythmias, congestive heart failure, or myocardial infarction within the past 6 months

Other:

• Not pregnant or nursing (during and for at least 2 months after study)
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 2 months after study
• No concurrent serious or uncontrolled infection
• HIV negative
• No other medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior immunotherapy and recovered

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• Prior irinotecan allowed

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• See Disease Characteristics

Other:

• Recovered from prior therapy
• No other concurrent investigational medication
• No concurrent vitamins (except a single multivitamin tablet), antioxidants, or herbal preparations or supplements
• No concurrent subcutaneous heparin or heparinoids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: September 1, 2000
• Primary Completion (Actual): December 1, 2003

Study Registration Dates

• First Submitted: November 6, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): December 15, 2009
• Last Update Submitted That Met QC Criteria: December 13, 2009
• Last Verified: June 1, 2003

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; Topoisomerase Inhibitors; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Topoisomerase I Inhibitors; Irinotecan; Alvocidib
• Other Study ID Numbers: CDR0000068316; MSKCC-00091; NCI-2272