Inclusion Criteria:

          1. Provision to sign and date the consent form (if individual is a minor, provision of a
             parent or legal guardian to sign and date the consent form and provision of individual
             to provide assent for study).

          2. Stated willingness to comply with all study procedures and be available for the
             duration of the study.

          3. Male or female aged 10-40 years old.

          4. Histologically confirmed osteosarcoma (at either original diagnosis or relapse) that
             has either recurred or progressed after at least one prior systemic therapy and for
             which no curative therapy exists.

               -  Patients with surface or periosteal osteosarcoma are not eligible.

               -  Patients with active CNS metastasis are not eligible. Previously treated CNS
                  metastases which occurred 3 months or more prior, without evidence of active
                  recurrence, are acceptable.

          5. Disease status

               -  Dose Escalation (Part A): Patients must have measurable or evaluable disease.

               -  Cohort Expansion (Part B): Patients with measurable or evaluable disease and
                  those with completely resected disease are eligible.

          6. Performance status:

             • ECOG performance status (>18 years old) ≤ 2 or Karnofsky performance score (<18
             years old) > 50.

          7. Prior Therapy:

               -  Patients must have fully recovered from the acute toxic effects of all prior
                  anti-cancer therapy and must meet the following minimum duration from prior
                  anti-cancer directed therapy prior to enrollment. If after the required
                  timeframe, the numerical eligibility criteria are met (e.g., blood count
                  criteria) the patient is considered to have recovered adequately.

                    -  Cytotoxic chemotherapy or other anti-cancer agents known to be
                       myelosuppressive. At least 21 days after the last dose of cytotoxic or
                       myelosuppressive chemotherapy (42 days if prior nitrosourea).

                    -  Anti-cancer agents not known to be myelosuppressive (e.g. not associated
                       with reduced platelet or ANC counts): ≥ 7 days after the last dose of agent.

                    -  Antibodies: ≥ 21 days must have elapsed from infusion of last dose of
                       antibody, and toxicity related to prior antibody therapy must be recovered
                       to Grade ≤ 1.

                    -  Corticosteroids: ≥ 14 days must have elapsed since last dose of
                       corticosteroid.

                    -  Hematopoietic growth factors: ≥ 14 days after the last dose of a long-
                       acting growth factor (e.g., pegfilgrastim) or 7 days for short-acting growth
                       factor.

                    -  Interleukins, Interferons and Cytokines (other than hematopoietic growth
                       factors): ≥ 21 days after the completion of interleukins, interferon or
                       cytokines (other than Hematopoietic Growth Factors).

                    -  Stem cell Infusions: Autologous stem cell infusion, including boost
                       infusion: ≥ 42 days.

                    -  Cellular Therapy: ≥ 42 days after the completion of any type of cellular
                       therapy (e.g., modified T cells, NK cells, dendritic cells, etc.)

                    -  XRT/External Beam Irradiation including protons: ≥ 14 days after local XRT;
                       ≥ 150 days after TBI, craniospinal XRT or if radiation to ≥ 50% of the
                       pelvis; ≥ 42 days if other substantial bone marrow radiation.

               -  NOTE: Patients with history of cardiac irradiation with mean cardiac dose > 15 Gy
                  are not eligible (see exclusion criteria).

          8. Adequate bone marrow function, defined as:

               -  Peripheral absolute neutrophil count (ANC) ≥ 750/mm3

               -  Platelet count ≥ 75,000/mm3 (transfusion independent, defined as not receiving
                  platelet transfusions for at least 7 days prior to enrollment).

               -  Hemoglobin ≥ 8 g/dL (with or without transfusion)

          9. Adequate renal function, defined as:

             • Creatinine clearance or radioisotope GFR > 70 mL/min/1.73 m2 OR a serum creatinine
             based on age/gender as follows:

             Age 2 to <6: Male=0.8, Female=0.8; Age 6 to <10: Male=1, Female=1; Age 10 to <13:
             Male=1.2, Female=1.2; Age 13 to <16: Male=1.5, Female=1.4; Age >/= to 16: Male=1.7,
             Female=1.4

         10. Adequate hepatic function, defined as:

               -  Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age

               -  SGPT (ALT) ≤ 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.

               -  Serum albumin ≥ 2.8 g/dL

         11. Adequate cardiac function, defined as:

               -  Current cardiac ejection fraction ≥ 50% by biplane Simpson method on
                  echocardiogram

               -  QTc ≤ 480 ms

         12. Patients with preexisting hyper- or hypothyroidism must be on a stable dose of
             medication.

         13. Ability to take and retain oral medications. NOTE: Medication can be administered via
             nasogastric or gastrostomy tube.

        Exclusion Criteria:

          1. Patients who underwent major surgery within 14 days prior to start of treatment are
             not eligible. NOTE: Core biopsy or central line placement are considered minor and are
             allowed within any time limitations.

          2. Patients with uncontrolled coagulopathy or bleeding disorder, or any active bleeding
             (i.e. gastrointestinal or pulmonary) deemed to be clinically significant by
             investigator are not eligible.

          3. Patients with history of pulmonary embolism or significant thromboembolic event with
             the preceding 28 days. Patients with thromboembolic events > 28 days before enrollment
             who are stable on or completed an anticoagulation course are eligible.

          4. Patients with history of cardiac irradiation with mean cardiac dose > 15 Gy are not
             eligible.

          5. Patients with symptomatic cardiac disease (i.e. New York Heart Association or Modified
             Ross Heart Failure Classification for Children > class 2) are not eligible.

          6. Patients with any history of cardiac dysfunction including prior abnormal
             echocardiogram (ejection fraction < 50%), severe or unstable angina, peripheral
             vascular disease, congenital prolonged QTc syndrome, clinically significant cardiac
             arrhythmias, stroke, or myocardial infarction are not eligible.

          7. Pregnancy

               -  Pregnant or breast-feeding women will not be entered on this study because there
                  is not yet available information regarding human fetal or teratogenic toxicities.
                  Pregnancy tests must be obtained in females who are post-menarchal.

               -  Males or females of reproductive potential may not participate unless they have
                  agreed to practice 1 highly effective and 1 additional effective (barrier) method
                  of contraception at the same time during the entire study treatment period and
                  through 3 months after the last dose of study drug, or agree to practice true
                  abstinence, when this is in line with the preferred and usual lifestyle of the
                  subject. Patients who themselves or their partners have undergone female or male
                  sterilization do not require 2 methods of contraception. Highly effective methods
                  are defined as those with <1% failure rate with perfect use and include: oral
                  contraceptive pills (combined or progesterone only), intrauterine devices (IUD),
                  hormonal implant or injection, contraceptive patch, and vaginal ring.

          8. Concomitant medications:

               -  Anti-hypertensives: Patients requiring more than one antihypertensive medication
                  to control blood pressure, or have baseline blood pressure > 95th percentile for
                  age are not eligible (see Appendix VIII).

               -  Corticosteroids: Patients receiving systemic corticosteroids are not eligible. >
                  14 days must have elapsed since last systemic corticosteroid. Note: patients
                  using topical or inhaled corticosteroids are eligible.

               -  Investigational Drugs: Patients currently receiving another investigational drug
                  are not eligible.

               -  Anti-cancer agents: Patients currently receiving other anti-cancer agents are not
                  eligible.

               -  Drug interactions: Patients who require treatment with medications that are
                  strong inhibitors or inducers of CYP3A4 or inhibitors of CYP2A9 or have received
                  these medications in the 7 days prior to enrollment, are not eligible. Patients
                  who require treatment with enzyme inducing anticonvulsants are not eligible (see
                  Appendix III).

               -  Medications that prolong QTc: Patients who require treatment with medications
                  known to prolong QTc are not eligible