Irinotecan and Flavopiridol in Treating Patients With Advanced Liver Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as irinotecan and flavopiridol, 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. PURPOSE: This phase II trial is studying how well giving irinotecan together with flavopiridol works in treating patients with advanced liver cancer.

Detailed Description
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OBJECTIVES: Primary Determine the time to progression in patients with advanced hepatocellular carcinoma treated with irinotecan and flavopiridol. Secondary Determine the response rate and overall survival in patients treated with this regimen. Determine the toxicity of this regimen in these patients. OUTLINE: This is an open-label, non-randomized study. Patients receive irinotecan IV over 30 minutes and flavopiridol IV over 1 hour on days 1, 8, 15, and 22. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 16-32 patients will be accrued for this study within 2 years.

Official Title
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A Non-Randomized Phase II Study of Sequential Irinotecan (CPT-11) And Flavopiridol In Patients With Advanced Hepatoma

Conditions
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Liver Cancer

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 or cytologically confirmed hepatocellular carcinoma Advanced disease Measurable disease At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan Prior local therapy (e.g., surgery, hepatic arterial embolization, radiofrequency ablation, or cryoablation) allowed provided therapy was completed ≥ 8 weeks before study entry AND ≥ 1 of the following conditions are met: Target lesion was not subjected to local therapy 25% increase in the size of target lesion within the field of prior local therapy Lesions treated with external beam radiotherapy are not acceptable as target lesions Child-Pugh class A or B status if liver cirrhosis is present Score 7 or 8 only No known brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 70-100% Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 75,000/mm^3 WBC ≥ 3,000/mm^3 Hepatic See Disease Characteristics AST and ALT ≤ 2.5 times upper limit of normal Bilirubin ≤ 1.5 mg/dL Renal Creatinine normal OR Creatinine clearance ≥ 60 mL/min Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No deep vein thrombosis within the past 6 months Patients maintained on anticoagulation therapy for an event that occurred more than 6 months ago are eligible No myocardial infarction within the past 6 months No cardiac arrhythmia within the past 6 months Rate-controlled atrial fibrillation allowed if stable for at least 6 months Pulmonary No pulmonary embolus within the past 6 months Patients maintained on anticoagulation therapy for an event that occurred more than 6 months ago are eligible Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study participation No prior allergic reaction attributed to compounds of similar chemical or biological composition to flavopiridol or irinotecan No clinically significant gastrointestinal bleeding requiring hospitalization within the past month No active or ongoing infection No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness No other malignancy within the past 3 years except carcinoma in situ of the cervix, adequately treated basal cell skin cancer, or superficial bladder tumors [Ta, Tis, or T1] PRIOR CONCURRENT THERAPY: Biologic therapy No prior systemic biologic therapy Chemotherapy No prior systemic chemotherapy for hepatocellular carcinoma No other concurrent chemotherapy Endocrine therapy Not specified Radiotherapy See Disease Characteristics Surgery See Disease Characteristics No prior organ allograft Other No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent vitamins, antioxidants, or herbal preparations and supplements Single-tablet multivitamin allowed No other concurrent investigational agents No other concurrent anticancer agents or therapies

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
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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adult primary hepatocellular carcinoma, advanced adult primary liver cancer, recurrent adult primary liver cancer