INCLUSION CRITERIA:
Patients must be less than 22 years of age at the time of study entry.
Patients must have had histologic verification of the solid ttumor/malignancy at the time of original diagnosis (excluding brain sten and optic pathway tumors).
The following histologies are eligible:
All brain tumors
Osteogenic sarcoma
Rhabdomyosarcoma
Soft tissue sarcomas (excluding Ewing's)
Neuroblastomas
Germ cell tumors
Patient's disease must be one for which there is no curative therapy.
Karnofsky greater than or equal to 50% for patients greater than 10 years of age and Lansky greater than or equal to 50 for patients less than or equal to 10 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
Life Expectancy: Must be greater than or equal to 8 weeks.
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
a. Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study (4 weeks if prior nitrosourea).
b. Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent.
c. XRT: greater than or equal to 2 wks for local palliative XRT (small port): greater than or equal to 6 months must have elapsed if prior craniospinal XRT or if greater than or equal to 50% of the pelvis has been radiated; greater than or equal to 6 wks must have elapsed if other substantial BM radiation. Patients with recurrent brain tumors should be greater than or equal to 8 weeks from completion of standard fraction radiation unless there is biopsy proof of the presence of recurrent tumor. Patients who underwent radiosurgery within 9 months must have documentation of progressive disease either by biopsy, PET scan or MR spectroscopy.
d. Stem Cell Transplant (SCT): No evidence of active graft vs. host disease and greater than or equal to 3 months must have elapsed.
Concomitant Medications:
a. Growth factor(s): Must not have received within 1 week of entry onto this study.
b. Steroids: Systemic corticosteroid therapy is permissible only in patients with CNS tumors for treatment of increased intracranial pressure or symptomatic tumor edema. Patients with CNS tumors who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to study entry.
c. Study Specific: Patients on enzyme-inducing anticonvulsants will not be allowed on this study. Patients receiving protonpump inhibitor or H2 blockers will not be allowed on study. Patients taking antacids will be allowed on study although they should not take the antacid for two hours before or two hours after taking OSI-774.
Patients should not have received a CYP3A4 inhibitor within 1 week of study entry and should not have received a CYP3A4 inducer within 4 weeks of study entry.
Organ Function Requirements:
Adequate Bone Marrow Function Defined as:
For patients with solid tumors including status post SCT:
-Peripheral absolute neutrophil count (ANC) greater than 1000/microL
-Platelet count greater than 100,000/microL (transfusion independent, i.e. patients must not have received platelet transfusions within 7 days of enrollment)
-Hemoglobin greater than 8.0 gm/dL (may receive RBC transfusions)
Adequate Renal Function Defined As:
-Creatinine clearance or radioisotope GFR greater than or equal to 70ml/min/m(2) OR:
-A serum creatinine based on age as follows:
Age (Years) of less than or equal to 5 and a Maximum Serum Creatinine (mg/dL) of 0.8
Age greater than 5, but less than or equal to 10 and a Maximum Serum Creatinine (mg/dL) of 1.0
Age greater than 10, but less than or equal to 15 and a Maximum Serum Creatinine (mg/dL) of 1.2
Age greater than 15 and a Maximum Serum Creatinine (mg/dL) of 1.5
Adequate Liver Function Defined As:
-Total bilirubin less thsn 1.5 x upper limit of normal (ULN) for age,
and
-SGPT (ALT) less than 2.5 x upper limit of normal (ULN) for age and albumin greater than or equal to 2 g/dL.
EXCLUSION CRITERIA:
Pregnancy or Breast-Feeding.
Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
Patients who have an uncontrolled infection.
Patients who have previously received OSI-774.
Patients with third space fluid collections (e.g. pleural or pericardial effusions or ascites).
Patients receiving enzyme-inducing anticonvulsants.
Patients who have received any proton-pump inhibitors within 5 days of study entry or H2 blockers within 2 days of study entry.
Patients who have received a CYP3A4 inhibitor within 1 week of study entry or a CYP3A4 inducer within 4 weeks of study entry.
Exclusion Criteria for Less Heavily Treated Stratum:
Based on preclinical toxicology and adult Phase I data, we do not expect OSI-774 to cause myelosuppression. However, temozolomide frequently causes myelosuppression, particularly in heavily pretreated patients. Therefore, if myelosuppression is a dose-limiting toxicity for at least two patients at any dose level in the first course of the combination phase, then the protocol will henceforth exclude:
Patients who have received more than two prior multi-agent myelosuppressive chemotherapy regimens.
Patients who have had prior craniospinal or pelvic radiation or bone marrow transplantation
Patients with bone marrow involvement.
Regulatory:
All patients and/or their parents or legal guardians must sign a written informed consent.
All institutional, FDA, and NCI requirements for human studies must be met.
Warren Grant Magnuson Clinical Center (CC)