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

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: alvocidib; Drug: gemcitabine hydrochloride; Drug: irinotecan hydrochloride	Phase 1

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	24 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase I Study of Flavopiridol in Combination With Gemcitabine and Irinotecan in Patients With Metastatic Cancer
Study Start Date :	April 2004
Actual Primary Completion Date :	October 2007

Arms and Interventions

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Arm	Intervention/treatment
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

Outcome Measures

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Primary Outcome Measures :

1. 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 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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

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Locations

United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87106

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Ian Rabinowitz	University of New Mexico

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00079352 History of Changes
Other Study ID Numbers:	NCI-2012-02580; UNM-0903C; CDR0000355358 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted:	March 10, 2004
Last Update Posted:	January 25, 2013
Last Verified:	January 2013

Additional relevant MeSH terms:

Gemcitabine; Irinotecan; Camptothecin; Alvocidib; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents	Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents, Phytogenic; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Growth Inhibitors; Growth Substances; Protein Kinase Inhibitors