A Phase I Study of Temozolomide, Oral Irinotecan, and Vincristine for Children With Refractory Solid Tumors

ADVL0414

RATIONALE: Drugs used in chemotherapy, such as temozolomide, vincristine, and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan when given together with temozolomide and vincristine in treating young patients with refractory solid tumors.

2005-10-01

2009-06-01

2011-01-01

Completed

Early phase I

42

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 42, 'type': 'ACTUAL'}}

2023-10-02