Flavopiridol and Irinotecan in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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An Open-Labeled, Non-Randomized Phase I Study Of Flavopiridol Administered With Irinotecan (CPT-11) In Patients With Advanced Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: alvocidib
* Drug: irinotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: alvocidib|nan|
|Drug: irinotecan hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific