Irinotecan and Selenium in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Selenium may allow higher doses of irinotecan to be given. Giving irinotecan together with selenium may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of selenium when given together with irinotecan in treating patients with advanced solid tumors.

Detailed Description
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OBJECTIVES: Primary Determine the optimal loading and maintenance doses of selenium necessary to achieve selenium concentrations exceeding 15 μM when administered with irinotecan in patients with advanced solid tumors. Secondary Determine the pharmacokinetics of this regimen in these patients. Determine the toxic effects of this regimen in these patients. Determine any observed tumor response to this regimen in these patients. OUTLINE: This is a dose-escalation study of selenium. Patients receive a loading dose* of oral selenium twice daily on days -6 to 0. Patients then receive oral selenium once daily on days 1-42 and irinotecan IV over 90 minutes on days 1, 8, 15, and 22. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. NOTE: *The loading dose is administered prior to course 1 only. Cohorts of 3-6 patients receive escalating doses of selenium until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. PROJECTED ACCRUAL: A total of 2-36 patients will be accrued for this study within 18 months.

Official Title
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A Phase I and Pharmacokinetic Study of Selenomethionine With Fixed Dose Irinotecan in Advanced Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Dietary Supplement: selenium
* Drug: irinotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed solid tumor Metastatic or unresectable disease Standard curative or palliative treatments do not exist or are no longer effective OR treatment with single-agent irinotecan does not constitute a reasonable treatment option No known untreated or progressive brain metastases Previously treated brain metastases allowed provided all of the following are true: No significant neurological deficit No requirement for anti-epileptic medications Disease stable by brain CT scan or MRI PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy At least 12 weeks Hematopoietic WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin normal AST and ALT ≤ 3 times upper limit of normal Albumin ≥ 3.0 g/dL No Gilbert's disease Renal Creatinine normal OR Creatinine clearance ≥ 60 mL/min Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No clinically significant cardiac arrhythmia Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Able to receive oral medications No active inflammatory bowel disease or chronic diarrhea No known HIV positivity No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study drugs No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF) Chemotherapy At least 4 weeks since prior chemotherapy (6 weeks for carmustine or mitomycin) Endocrine therapy Not specified Radiotherapy At least 4 weeks since prior radiotherapy Surgery Not specified Other No other concurrent investigational agents No other concurrent anticancer therapy No concurrent Hypericum perforatum (St. John's wort)

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Dietary Supplement: selenium|nan|
|Drug: irinotecan hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose |  |  | 

 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