Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors

You may be eligible if

• DISEASE CHARACTERISTICS:
• Histologically confirmed malignant solid tumor that did not respond to or relapsed after standard first-line chemotherapy or other antineoplastic therapy (if the standard therapy for the tumor is generally recognized to be beneficial)
• * Must have been initially diagnosed with malignancy prior to 25 years of age
• * Radiographic, nuclear image, or biopsy confirmation of disease within the past 4 weeks
• Meets one of the following criteria:
• * Phase I: Relapsed/refractory malignant solid tumor (excluding CNS tumors)
• * Patients with recurrent or metastatic disease that was completely resected just prior to study entry are eligible
• * Phase II: Patients are stratified according to one of the following diagnoses:
• * Stratum A: Relapsed sarcoma (rhabdomyosarcoma, osteosarcoma, or Ewing sarcoma)
• * Stratum B: Other relapsed solid tumors, including any of the following:
• * Other soft tissue sarcomas
• * Kidney tumors
• * Lymphoma
• * CNS tumors\*
• * Other solid tumors (neuroblastoma, gonadal and germ cell tumors, liver tumors, or miscellaneous tumors)
• * Stratum C: Newly diagnosed, poor-risk metastatic sarcoma consisting of unresectable pulmonary metastases (≥ 6 nodules) and/or disease involving multiple bones or other organs NOTE: \*Patients with recurrent primary CNS tumors are eligible for the phase II portion of this study provided there are no significant intratumoral bleeding toxicities seen in either COG pediatric phase I studies of dasatinib or the phase I portion of this study
• Radiographically measurable disease (Phase II)
• * Measurable disease is not required for patients who are enrolled in the phase I portion of this study
• No bone marrow involvement (Phase I)
• * Patients with bone marrow involvement are eligible for the phase II portion of this study provided they are not known to be refractory to red cell or platelet transfusions
• PATIENT CHARACTERISTICS:
• Lansky performance status (PS) 50-100% (patients 1-16 years of age) or Karnofsky PS 50-100% (patients \> 16 years of age)
• Life expectancy ≥ 8 weeks
• ANC \> 1,000/μL
• Platelet count \> 75,000/μL
• Creatinine clearance or GFR ≥ 70 mL/min OR creatinine \< 1.5 times upper limit of normal (ULN)
• Bilirubin \< 1.5 times ULN for age
• SGOT or SGPT \< 2.5 times ULN for age (\< 5 times ULN if liver involvement by tumor)
• Ejection fraction normal by MUGA OR shortening fraction \> 28%
• No evidence of cardiac arrhythmias requiring therapy
• Corrected QTc interval \< 450 msecs
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to comply with the safety monitoring requirements of this study
• No uncontrolled infection
• No swallowing dysfunction that would preclude oral medication intake
• * Gastric or jejunal tube allowed provided it is functioning
• No history of significant bleeding disorder unrelated to cancer, including the following:
• * Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
• * Acquired bleeding disorder diagnosed within the past year (e.g., acquired anti-factor VIII antibodies)
• * Ongoing or recent (within the past 3 months) significant gastrointestinal bleeding
• PRIOR CONCURRENT THERAPY:
• See Disease Characteristics
• Recovered from all prior therapy
• At least 7 days since prior and no concurrent drugs known to cause Torsades de Pointes, including the following:
• * Procainamide or disopyramide
• * Amiodarone, sotalol, ibutilide, or dofetilide
• * Erythromycin or clarithromycin
• * Chlorpromazine, haloperidol, mesoridazine, or thioridazine
• * Bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, or lidoflazine
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosourea-containing therapy)
• At least 3 months since prior ifosfamide, carboplatin, and/or etoposide phosphate in the exact combination and dosage as administered in this study
• More than 7 days since prior filgrastim (G-CSF), sargramostim (GM-CSF), or interleukin-11
• More than 14 days since prior pegfilgrastim
• More than 30 days since prior epoetin alfa
• No prior cranial-spinal irradiation at doses \> 2,400 cGy
• No prior radiotherapy, including total-body irradiation, to \> 50% of the bone marrow space
• No other concurrent investigational drugs or anticancer agents
• No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, phenobarbital, felbamate, primdone, oxcarbazepine, or carbamazepine)
• No concurrent anti-thrombotic or anti-platelet agents (e.g., warfarin, heparin, low molecular weight heparin, aspirin, ibuprofen, or other NSAIDs)
• No concurrent CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, or voriconazole)
• No concurrent highly active antiretroviral therapy for HIV-positive patients
• No concurrent St. John's wort
• No IV bisphosphonates during the first 8 weeks of dasatinib therapy