Flavopiridol, Gemcitabine, and Irinotecan in Treating Patients With Unresectable or Metastatic Solid Tumors - Full Text View

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:

Drug Information available for: Gemcitabine Irinotecan Irinotecan hydrochloride Gemcitabine hydrochloride

U.S. FDA Resources

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 (Adult, Senior)
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

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Ian Rabinowitz	University of New Mexico

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
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 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

ClinicalTrials.gov processed this record on September 23, 2016