Irinotecan in Treating Children With Refractory or Advanced Solid Tumors Who Are Receiving Anticonvulsants

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of irinotecan in treating children with refractory or advanced solid tumors who are receiving anticonvulsants.

OBJECTIVES:

* Determine the maximum tolerated dose of irinotecan in children with refractory or advanced solid tumors receiving anticonvulsants.
* Determine the dose-limiting toxicity of irinotecan in this patient population.
* Evaluate the pharmacokinetic behavior of this treatment regimen in these patients.
* Determine, preliminarily, the antitumor activity of this treatment regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to type of concurrent anticonvulsant (enzyme activating anticonvulsants vs valproic acid vs other anticonvulsants).

Patients receive irinotecan IV over 1 hour daily for 5 days. Treatment repeats 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 reached. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 6 months for up to 4 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 3-25 patients will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed malignancy refractory to conventional therapy or for which no conventional therapy exists

  * Histologic confirmation not required for brain stem tumors
* Concurrently on anticonvulsants at a steady level for at least 2 weeks

PATIENT CHARACTERISTICS:

Age:

* 1-21 years old

Performance status:

* Karnofsky 50-100% (over 10 years of age)
* Lansky 50-100% (10 years of age or under)

Life expectancy:

* At least 8 weeks

Hematopoietic:

* Neutrophil count at least 1,000/mm3
* Platelet count at least 100,000/mm3 (transfusion independent)
* Hemoglobin at least 8.0 g/dL (red blood cell transfusions allowed)

Hepatic:

* Bilirubin no greater than 1.5 times normal for age
* SGPT less than 5 times normal for age
* Albumin at least 2 g/dL

Renal:

* Creatinine no greater than 1.5 times normal for age OR
* Creatinine clearance or radioisotope glomerular filtration rate at least lower limit of normal for age

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No uncontrolled infection
* No evidence of active graft-vs-host disease
* Neurologic deficits for CNS tumors stable for at least 2 weeks prior to study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 1 week since prior antineoplastic biologic therapy
* At least 6 months since prior allogeneic stem cell transplantation
* At least 1 week since prior growth factors
* No concurrent sargramostim (GM-CSF)
* No concurrent prophylactic growth factors during first course of study therapy
* Recovered from prior immunotherapy

Chemotherapy:

* At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosourea) and recovered

Endocrine therapy:

* Concurrent dexamethasone for CNS tumors with increased intracranial pressure allowed if dose stable or decreasing for at least 2 weeks prior to study

Radiotherapy:

* At least 2 weeks since prior local palliative radiotherapy (small part)
* At least 6 months since prior craniospinal radiotherapy
* At least 6 months since prior radiotherapy to at least 50% of pelvis
* At least 6 weeks since prior substantial bone marrow radiotherapy
* Recovered from prior radiotherapy

Surgery:

* Not specified

Other:

* No other concurrent investigational agent