Flavopiridol and Irinotecan in Treating Patients With Advanced Solid Tumors

Memorial Sloan Kettering Cancer Center

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Interventions

alvocidibDRUG

irinotecan hydrochlorideDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Data from ClinicalTrials.gov

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