Flavopiridol, Gemcitabine, and Irinotecan in Treating Patients With Unresectable or Metastatic Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00079352
First received: March 8, 2004
Last updated: January 24, 2013
Last verified: January 2013
  Purpose

This phase I trial is studying the side effects and best dose of flavopiridol when given together with gemcitabine and irinotecan in treating patients with unresectable or metastatic solid tumors. Drugs used in chemotherapy, such as flavopiridol, gemcitabine, and irinotecan, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: alvocidib
Drug: gemcitabine hydrochloride
Drug: irinotecan hydrochloride
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Flavopiridol in Combination With Gemcitabine and Irinotecan in Patients With Metastatic Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Recommended phase II dose of flavopiridol defined as the highest dose for which no more than one patient develop a >= grade 3 toxicity [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: April 2004
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (gemcitabine, irinotecan, alvocidib)
Patients receive gemcitabine IV over 30 minutes followed by irinotecan IV over 30 minutes on days 1 and 15. Patients also receive flavopiridol IV over 60 minutes on days 2 and 16. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: alvocidib
Given IV
Other Names:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose and recommended phase II dose of flavopiridol in combination with gemcitabine and irinotecan in patients with unresectable or metastatic solid tumors.

II. Determine the toxicity profile of this regimen in these patients.

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

Patients receive gemcitabine IV over 30 minutes followed by irinotecan IV over 30 minutes on days 1 and 15. Patients also receive flavopiridol IV over 60 minutes on days 2 and 16. Treatment repeats every 28 days for up to 6 courses 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 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed solid tumor that is metastatic or unresectable
  • Standard curative or palliative measures do not exist or are no longer effective
  • No known brain metastases
  • Performance status - ECOG 0-2
  • Performance status - Karnofsky 60-100%
  • More than 12 weeks
  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin normal
  • AST and ALT ≤ 2.5 times upper limit of normal
  • Creatinine normal
  • Creatinine clearance ≥ 60 mL/min
  • No venous thrombosis within the past 6 months
  • No thrombotic cerebrovascular accident within the past 6 months
  • No myocardial infarction within the past 6 months
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • No ongoing or active infection
  • No prior allergic reaction attributed to compounds of similar chemical or biological composition to study agents
  • No other concurrent uncontrolled medical condition that would preclude study participation
  • No psychiatric illness or social situation that would preclude study participation
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Prior biologic therapy allowed
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • Prior endocrine therapy allowed
  • More than 4 weeks since prior radiotherapy and recovered
  • Prior surgery allowed
  • No other concurrent investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00079352

Locations
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87106
Sponsors and Collaborators
Investigators
Principal Investigator: Ian Rabinowitz University of New Mexico
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00079352     History of Changes
Other Study ID Numbers: NCI-2012-02580, UNM-0903C, CDR0000355358
Study First Received: March 8, 2004
Last Updated: January 24, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Gemcitabine
Irinotecan
Camptothecin
Flavopiridol
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Growth Inhibitors
Growth Substances
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014