Clinical Trial Finder

DISEASE CHARACTERISTICS:

• - Histologically confirmed* malignant solid tumor, including brain tumor, at original diagnosis or relapse.

• - Refractory disease NOTE: *Histologic confirmation not required for intrinsic brain stem tumors.

• - Measurable or evaluable disease.

• - No known curative therapy OR therapy proven to prolong survival with an acceptable quality of life exists.

• - No known bone marrow metastases.

PATIENT CHARACTERISTICS: Age.

• - 1 to 21.

Performance status.

• - Lansky 50-100% (for patients ≤ 10 years of age) - Karnofsky 50-100% (for patients > 10 years of age) Life expectancy.

• - Not specified.

Hematopoietic.

• - Absolute neutrophil count ≥ 1,000/mm^3.

• - Platelet count ≥ 100,000/mm^3 (transfusion independent) - Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed) Hepatic.

• - ALT ≤ 110 U/L (upper limit of normal [ULN] for ALT is 45 U/L) - Bilirubin ≤ 1.5 times ULN.

• - Albumin ≥ 2 g/dL.

Renal.

• - Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR.

• - Creatinine based on age as follows: - No greater than 0.8 mg/dL (for patients ≤ 5 years of age) - No greater than 1.0 mg/dL (for patients 6 to 10 years of age) - No greater than 1.2 mg/dL (for patients 11 to 15 years of age) - No greater than 1.5 mg/dL (for patients > 15 years of age) Other.

• - Not pregnant or nursing.

• - Negative pregnancy test.

• - Fertile patients must use effective contraception.

• - Neurologic deficits in patients with CNS tumors must be stable for ≥ 1 week prior to study entry.

• - No uncontrolled infection.

• - No documented allergy to cephalosporins or dacarbazine.

PRIOR CONCURRENT THERAPY: Biologic therapy.

• - Recovered from prior immunotherapy.

• - At least 3 months since prior stem cell transplantation or rescue without total-body irradiation.

• - No evidence of active graft-versus-host disease.

• - At least 7 days since prior antineoplastic biologic agents.

• - At least 7 days since prior hematopoietic growth factors.

• - No concurrent biologic therapy or immunotherapy.

• - No concurrent prophylactic filgrastim (G-CSF) during the first course of study treatment.

Chemotherapy.

• - Recovered from prior chemotherapy.

• - Prior temozolomide, vincristine, irinotecan, or topotecan allowed.

• - No prior coadministration of temozolomide and irinotecan.

• - No disease progression during treatment with either irinotecan or temozolomide.

• - More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) - No other concurrent chemotherapy.

Endocrine therapy.

• - Patients with CNS tumors must be on a stable or decreasing dose of dexamethasone for ≥ 7 days prior to study entry.

Radiotherapy.

• - Recovered from prior radiotherapy.

• - At least 6 months since prior total-body irradiation, craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis.

• - At least 6 weeks since other prior substantial bone marrow radiotherapy.

• - At least 2 weeks since prior local palliative radiotherapy (small port) - No concurrent radiotherapy.

Surgery.

• - Not specified.

Other.

• - No other concurrent investigational drugs.

• - No other concurrent anticancer therapy.

• - No concurrent enzyme-inducing anticonvulsants, including any of the following: - Phenobarbital.

• - Phenytoin.

• - Carbamazepine.

• - Oxcarbazepine.

• - No concurrent administration of any of the following: - Rifampin.

• - Voriconazole.

• - Itraconazole.

• - Ketoconazole.

• - Aprepitant.

- Hypericum perforatum (St. John's wort) - No concurrent treatment for clostridium difficile infection

OBJECTIVES: Primary.

• - Determine the maximum tolerated dose and recommended phase II dose of irinotecan when administered with temozolomide and vincristine in young patients with refractory solid tumors, including brain tumors.

• - Determine the toxic effects of this regimen in these patients.

• - Compare the toxic effects of this regimen in patients with low- vs.#46;high-risk UGT1A1 genotypes.

• - Determine the pharmacokinetics of irinotecan in these patients.

Secondary.

• - Determine, preliminarily, the antitumor activity of this regimen in these patients.

• - Correlate UGT1A1, UGT1A7, UGT1A9, and BCRP genotypes with the pharmacokinetics and pharmacodynamics of irinotecan and its metabolites in these patients.

OUTLINE: This is a multicenter, dose-escalation study of irinotecan. Patients are stratified according to UGT1A1 genotype (high-risk [7/7 or 6/7 genotype AND bilirubin ≥ 0.6 mg/dL] vs.#46;low-risk [absence of high-risk criteria]) if a high-risk patient experiences a dose-limiting toxicity (DLT). Patients receive oral temozolomide on days 1-5 and oral irinotecan on days 1-5 and 8-12. Patients also receive vincristine IV over 1 minute on days 1 and 8. Treatment repeats every 21 days for up to 17 courses 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 determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience DLT. After completion of study treatment, patients are followed for 1 month and then annually thereafter. PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 18 months.

Arms

Experimental: Oral Irinotecan, temozolomide and vincristine sulfate

see detailed description

Interventions

Drug: - irinotecan hydrochloride

Drug: - temozolomide

Drug: - vincristine sulfate