Flavopiridol and Irinotecan in Treating Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00006485
First received: November 6, 2000
Last updated: December 13, 2009
Last verified: June 2003

November 6, 2000
December 13, 2009
September 2000
December 2003   (final data collection date for primary outcome measure)
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Complete list of historical versions of study NCT00006485 on ClinicalTrials.gov Archive Site
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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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
Unspecified Adult Solid Tumor, Protocol Specific
  • Drug: alvocidib
  • Drug: irinotecan hydrochloride
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
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December 2003   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00006485
CDR0000068316, MSKCC-00091, NCI-2272
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Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
Study Chair: Gary K. Schwartz, MD Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
June 2003

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP