Gemcitabine Plus Flavopiridol in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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Phase I trial to study the effectiveness of gemcitabine plus flavopiridol in treating patients who have advanced solid tumors. 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.

Detailed Description
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OBJECTIVES: I. Determine the maximum tolerated dose of gemcitabine and flavopiridol in patients with advanced solid tumors. II. Determine the toxicity and safety profile of this regimen in these patients. III. Determine the pharmacokinetic profile of this regimen in this patient population. OUTLINE: This is a dose-escalation study. Patients receive gemcitabine IV over 1-2.5 hours on days 1 and 8 and flavopiridol IV continuously over 24 hours on days 2 and 9. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gemcitabine and flavopiridol until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. PROJECTED ACCRUAL: Approximately 6-58 patients will be accrued for this study.

Official Title
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A Phase I Trial Of Gemcitabine Followed By Flavopiridol In Patients With Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven solid tumor for which gemcitabine is a treatment option or for which no effective therapy exists Previously untreated disease allowed No large and potentially symptomatic pericardial effusion or undrained pleural effusion (with or without pleurodesis) No CNS metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 12 weeks Hematopoietic: Absolute neutrophil count at least 2,000/mm3 Platelet count at least 100,000/mm3 No prior thrombotic events Hepatic: Bilirubin no greater than 1.5 mg/dL SGOT no greater than 2 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL Cardiovascular: No clinically significant cardiac disease No prior deep venous thrombus No prior arterial vascular event No prior myocardial infarction No unstable angina No prior transient ischemic attack or cerebrovascular accident No cardiac arrhythmias that could be related to cardiac ischemia Pulmonary: No clinically significant pulmonary disease No history of pulmonary embolism Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active infection No severe malnutrition or intractable emesis No chronic diarrheal disease within the past 6 months PRIOR CONCURRENT THERAPY: Chemotherapy: No more than 1 prior chemotherapy regimen At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered Prior gemcitabine or flavopiridol allowed No other concurrent chemotherapy Radiotherapy: At least 3 weeks since prior radiotherapy and recovered No prior radiotherapy to more than 50% of bone marrow No concurrent radiotherapy

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive gemcitabine IV over 1-2.5 hours on days 1 and 8 and flavopiridol IV continuously over 24 hours on days 2 and 9. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gemcitabine and flavopiridol until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. | Drug: alvocidib<br> <br> Drug: gemcitabine hydrochloride<br> <br> |

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