| Inclusion Criteria: | 1) A subject must be 11 years of age or older and may be of any race, and gender (subjects between 4 and 10 years of age, inclusive, may be considered on a site-by-site basis).
2) A subject must have a diagnosis of histologically confirmed osteosarcoma or Ewing's sarcoma.
3) Group 1: Relapsed and resectable osteosarcoma that: has recurred after prior systemic treatment with active chemotherapy agents (eg, prior exposure to at least one chemotherapy regimen, ie, platinum and doxorubicin); and - must have had the confirmed relapse within 6 months of the immediate prior definitive treatment rendering the study in remission (eg, surgical metastasectomy) of the osteosarcoma (longer intervals require discussion with the sponsor).
4) Group 1 (continued): Must have a surgical or core biopsy tumor specimen (available to determine historical tumor proliferation), and the subject must not have been receiving tumor directed therapy at the time the specimen was obtained, or must have been progressing while on that treatment. The specimen should have been obtained within 8 months of study entry (specimens >8 months before study entry require discussion with the sponsor).
5) Group 2: Relapsed and resectable osteosarcoma that: has recurred after prior systemic treatment with active chemotherapy agents (eg, prior exposure to at least one chemotherapy regimen, ie, platinum and doxorubicin); and - must have had the confirmed relapse within 6 months of the immediate prior treatment of the osteosarcoma (longer intervals require discussion with the sponsor).
6) Group 3: Ewing's sarcoma that is refractory to standard systemic therapies (ie, prior treatment with at least 3 of these agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, and vincristine). The subject must have measurable disease on a CT or MRI study performed during Screening (within 21 days of Day 1).
7) A subject > 16 years of age must have an Eastern Cooperative Oncology Group (ECOG) performance status of < / = 2; a subject < / = 16 years of age must have a Karnofsky performance status between 50% and 100% or a Lansky play scale between 50% and 100%.
8) A subject must have a minimum life expectancy of > 8 weeks.
9) A subject must have adequate organ function within 3 weeks prior to Day 1 as evidenced by: a. hemoglobin > / = 9 g/dL, (> / = 8 g/dL in subjects with Ewing's sarcoma), b. absolute neutrophil count > / = 1.5 x 109/L, (> / = 1.0 x 109/L in subjects with Ewing's sarcoma), c. platelet count > / = 100 x 109/L, (> / = 50 x 109/L in subjects with Ewing's sarcoma), d. creatinine <1.5 x upper limit of normal (ULN) or creatinine clearance > / = 60 mL/min;
10) # 9, continued: e. total bilirubin <1.5 x ULN, except for subjects with Gilbert's disease, f. aspartate aminotransferase (AST)/serum glutamic-oxalacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) < 3 x ULN, or in the presence of documented liver metastases < / = 5 x ULN. Subjects with evidence of bone marrow involvement or single hematologic abnormalities (eg, ITP) may be permited on study on a case-by-case basis. Out-of-range laboratory values at Screening may be repeated once during the Screening Period.
11) A subject (and/or parent/guardian for subjects under the age of legal consent) must give written informed consent and be able to adhere to dose and visit schedules.
12) A female subject and a male subject's female partner, of childbearing potential, must agree to use a medically accepted method of contraception prior to Screening, while receiving protocol-specified medication, and for 2 months after stopping the medication. Acceptable methods of contraception include abstinence; oral, transdermal, or injectable hormonal contraceptive; and surgical sterilization (eg, hysterectomy or tubal ligation).
13) # 12, continued: Condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, and medically prescribed intrauterine devices may be acceptable according to local regulations. A woman of child-bearing potential who is not currently sexually active must agree to use a medically accepted method of contraception should she become sexually active while participating in the study. Any other tumor-directed therapy must be discussed with the sponsor on a case-by-case basis. |