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

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Drug: gemcitabine hydrochloride

Drug: alvocidib

Drug: irinotecan hydrochloride

Study type

Interventional

Funder types

NIH

Identifiers

NCT00079352

NCI-2012-02580

CDR0000355358 (Registry Identifier)

UNM-0903C

Details and patient eligibility

About

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

Full 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.

Enrollment

24 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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