Irinotecan and Selenium in Treating Patients With Advanced Solid Tumors

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.

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)