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.
- 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.
- 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
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.
- 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
- No known untreated or progressive brain metastases
- Previously treated brain metastases allowed provided all of the following are
- No significant neurological deficit
- No requirement for anti-epileptic medications
- Disease stable by brain CT scan or MRI
- 18 and over
- ECOG 0-1
- At least 12 weeks
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin normal
- AST and ALT ≤ 3 times upper limit of normal
- Albumin ≥ 3.0 g/dL
- No Gilbert's disease
- Creatinine normal OR
- Creatinine clearance ≥ 60 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No clinically significant cardiac arrhythmia
- 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:
- No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
- At least 4 weeks since prior chemotherapy (6 weeks for carmustine or mitomycin)
- Not specified
- At least 4 weeks since prior radiotherapy
- Not specified
- No other concurrent investigational agents
- No other concurrent anticancer therapy
- No concurrent Hypericum perforatum (St. John's wort)