Irinotecan and Selenium in Treating Patients With Advanced Solid Tumors

Roswell Park Comprehensive Cancer Center

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Drug: irinotecan hydrochloride

Dietary Supplement: selenium

Study type

Interventional

Funder types

Other

Identifiers

NCT00112892

RPCI-I-32804

CDR0000427616

Details and patient eligibility

About

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.

Full description

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.

Enrollment

36 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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