| Inclusion Criteria: | 1) AGE: >/= 2 years to < 18 years of age.
2) DIAGNOSES: Histologically confirmed solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, germ cell tumors, and primary brain tumors. In patients with brain stem or optic gliomas the requirement for histological confirmation can be waived if a biopsy was not performed.
3) TUMOR STATUS: Measurable or evaluable tumors. Patients with neuroblastoma that is only detectable by MIBG are eligible and considered to have measurable disease using the Curie scale. Patients with neuroblastoma that is only detected by bone marrow aspirate/biopsy are eligible and considered to have evaluable disease.
4) PRIOR THERAPY: The patient's cancer must have relapsed after or failed to respond to frontline curative therapy or there must not be other potentially curative treatment options available. Curative therapy may include surgery, radiation therapy, chemotherapy, or any combination of these modalities. Patients must have fully recovered to grade </=1 from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
5) Myelosuppressive chemotherapy: The last dose of all myelosuppressive anticancer drugs must be at least 3 weeks prior to study entry.
6) Biologic (anti-cancer agent): The last dose of all biologic agents for the treatment of the patient's cancer (such as retinoids) must be at least 7 days prior to study entry. The last dose of other monoclonal antibodies must be at least 30 days prior to study entry.
7) Investigational anti-cancer agent: The last dose of all investigational agents must be at least 30 days prior to study entry.
8) Radiation therapy: The last dose of radiation (including therapeutic ^131 MIBG) to more than 25% of marrow containing bones (pelvis, spine, skull) must be at least 4 weeks prior to study entry. The last dose of all other local palliative (limited port) radiation must be at least 2 weeks prior to study entry.
9) Stem Cell Transplantation. Patients must be at least 2 months post-autologous transplant and must have recovered from toxicities. Patients must be at least 6 months post-allogeneic transplant, must have recovered from toxicities, and must have no evidence of active graft-versus-host disease. Patients must also have been off of immunosuppressive treatment at least 30 days.
10) Number of prior treatment regimens: No limitation on the number of prior chemotherapy regimens that the patient may have received prior to study entry.
11) Colony stimulating factors: The last dose of colony stimulating factors, such as filgrastim, sargramostim, and epoetin, must be at least 48 hours prior to study entry, and the last dose of long-acting colony stimulating factors, such as pegfilgrastim, must be at least 10 days prior to study entry.
12) PERFORMANCE SCORE: 60-100 (Karnofsky scale, for patients >/=10 years of age) or 60-100 (Lansky scale, for children younger than 10 years of age).
13) HEMATOLOGIC FUNCTION: (a) Absolute neutrophil count (ANC) >/= 1.5 x 10^9/L; (b) Platelet count >/= 100 x 10\^9/L; (c) Patients with an ANC < 1.5 x 10^9/L or platelet count < 100 x 10^9/L due to bone marrow involvement by tumor or the effects of prior therapy are eligible only for the expanded cohort at the optimal dose/MTD on the qW schedule, but will not be evaluable for hematological toxicity. These patients should have an ANC > 0.5 x 10^9/L and a platelet count > 50 x 10^9/L.
14) RENAL FUNCTION: Age-adjusted normal serum creatinine OR a creatinine clearance >/= 60 mL/min/1.73 m^2 based on a 24 h urine collection. Normal Serum Creatinine in Children (maximum): 2 yrs to < 6 yrs: 0.8 mg/dl; 6 yrs to < 10 yrs: 1 mg/dl; 10 yrs to < 13 yrs: 1.2 mg/dl; 13 yrs to < 16 yrs: Male, 1.5 mg/dl, Female, 1.4 mg/dl; > 16 yrs: Male, 1.7 mg/dl, Female, 1.4 mg/dl.
15) HEPATIC FUNCTION: (a) Serum total bilirubin < 1.5 x ULN; (b) ALT/AST </= 2.5 x the ULN (</= 5 x the ULN for patients with known hepatic metastases).
16) CARDIAC FUNCTION: Left Ventricle Shortening fraction >/=28% (or equivalent left ventricular ejection fraction > 45%) by echocardiogram.
17) Patients with CNS metastases are eligible for enrollment if they have received prior surgical resection of or radiotherapy to site(s) of CNS disease and have been off corticosteroids for at least 4 weeks. Neurological deficits in these patients must have been stable for at least 4 weeks.
18) Patients enrolled on the dose escalation portion of the trial must being willing to participate in the pharmacokinetic studies that are performed on cycle 1, because this represents the primary endpoint of the trial. Pharmacokinetic studies are optional in patients enrolled in the expanded cohort at the optimal dose/MTD.
19) Patients and their legal representatives must be able to read, understand and provide written informed consent to participate in the trial.
20) Females of childbearing potential as well as fertile males and their partners must agree to use an effective form of contraception during the study and for 120 days following the last dose of study medication (effective forms of contraception include abstinence, a contraceptive or a double barrier method). |