Irinotecan and Gemcitabine in Treating Patients With Refractory 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 irinotecan with gemcitabine in treating patients who have refractory advanced solid tumors.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of irinotecan when administered with gemcitabine in patients with refractory advanced solid tumors. Determine the antitumor activity and toxicity of this regimen in these patients. Determine the pharmacokinetics and pharmacodynamics of this regimen in these patients. Determine the optimal dose and time interval for this regimen in these patients. OUTLINE: This is an open-label, non-randomized, dose-escalation study of irinotecan. Patients receive irinotecan IV over 90 minutes on days 1 and 8 and gemcitabine IV over 30 minutes 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 irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 8 weeks. PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study within 2 years.

Official Title
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Escalating Irinotecan (CPT-11) Administered 24 Hours Prior To Gemcitabine In Patients With Refractory Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed advanced solid tumor that is refractory to prior treatment Considered incurable with other modalities Measurable or evaluable disease The following are not considered measurable or evaluable: Bone metastases Pleural, pericardial, or peritoneal effusions Irradiated lesions (unless progression is documented after radiotherapy) Metastatic disease that has been followed using serum tumor markers allowed No symptomatic brain metastases Brain metastases may not be sole site of metastatic disease PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy At least 12 weeks Hematopoietic WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic AST and ALT no greater than 1.5 times normal Bilirubin no greater than 1.5 mg/dL No clinically apparent jaundice Renal Creatinine no greater than 1.6 mg/dL OR Creatinine clearance at least 50 mL/min Cardiovascular Cardiac function normal No uncontrolled heart disease No myocardial infarction within the past 3 months No congestive heart failure No unstable or uncontrolled angina Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix No active infection requiring systemic therapy No uncontrolled seizures No uncontrolled diabetes mellitus PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior gemcitabine No prior camptothecin compounds Prior irinotecan allowed No other concurrent chemotherapy Endocrine therapy Not specified Radiotherapy See Disease Characteristics At least 14 days since prior radiotherapy No concurrent radiotherapy Surgery Not specified Other More than 30 days since prior clinical trial participation No other concurrent investigational medications

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: gemcitabine hydrochloride|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