INCLUSION CRITERIA:
1. Patients must have histologically or cytologically confirmed
-Ewing's sarcoma (Ewing's family of tumors, ESFT)
---Ewing's sarcoma primary cohort (defined as those patients who have relapsed less than 24 months from diagnosis, and received at least 2 prior chemotherapy programs (one initial and a second for 1st relapse) and are unresectable).
---Ewing's sarcoma non-primary cohort ((defined as those patients who have relapsed greater than 24 months from diagnosis or have only received only 1 prior chemotherapy program.
-Osteosarcoma
-Synovial sarcoma
-Rhabdomyosarcoma
-Other sarcomas of the following subtypes:
---Alveolar soft part sarcoma
---Desmoplastic small round cell tumors
---Extraskeletal myxoid chondrosarcoma
---Clear cell sarcoma
---Myxoid Liposarcoma
2. Patients must have had histological verification of malignancy by central pathology review (to be completed within 6 weeks of study entry).
3. All patients must have recurrent or refractory tumors with no known curative treatment options according to the judgment of the investigator and must have documented progressive disease by WHO criteria.
4. Age greater than or equal to 2 years.
5. Life expectancy of at least 6 weeks.
6. Karnofsky performance status of greater than or equal to 70%.
7. Patients must have measurable disease defined as lesions that can be measured in 2 dimensions by medical imaging techniques such as CT or MRI. Ascites, pleural fluid, bone marrow disease and lesions seen on PET scan only are not considered measurable.
8. Adequate organ function requirements defined as:
8.a. Bone marrow (in the absence of bone marrow involvement by neoplasia).
1. Absolute neutrophil count greater than or equal to 1.5 times 10(9)/L (being greater than or equal to 2 weeks off growth factors.
2. Platelet count greater than or equal to 75,000/mL.
Note: in patients with documented (confirmed by bone marrow biopsy) bone marrow involvement by neoplasia, no minimum ANC or platelet count is necessary at the discretion of the investigator.
8b. Hepatic
1. Total bilirubin less than or equal to 1.5 times the upper limit of normal for age.
2. ALT /AST (SGPT/SGOT) less than or equal to 3 times the ULN for the reference lab (less than or equal to 5 times the ULN for the reference lab in the presence of known hepatic metastasis, adjusted for age).
8c. Renal
1. Creatinine clearance greater than or equal to 70 ml/min/1.73m(2) or
2. Serum creatinine less than 1.5 times ULN per age.
9. Prior Therapy
1. Time elapsed from previous therapy must be greater than or equal to 3 weeks. Patients must be recovered (toxicities less than grade 1 except for alopecia) from the effects of any prior surgery, radiotherapy or systemic therapy, including any investigational therapy.
2. Patients who have undergone autologous hematopoietic stem cell transplantation (HSCT) will be eligible once they have recovered from all toxicities from therapy (greater than or equal to grade 1 except for alopecia). Patients who have received allogeneic HSCT will be eligible 6 months after the procedure provided there is no evidence of active graft-versus-host disease and immunosuppressive treatment has been discontinued for at least 30 days.
3. Patients with central nervous system (CNS) disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS metastatic disease, have been off glucocorticoids for at least 4 weeks, have no overt evidence of neurological deficit and are greater than or equal to 6 weeks from completion of brain irradiation.
10. Patients or their legal representative must be able to read, understand and provide written informed consent to participate in the trial. Patients younger than 18 years of age should provide assent to participate in the trial.
11. 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. An effective form of contraception is use of an oral contraceptive, a double barrier method, or commitment to sexual abstinence.
12. Diabetic patients must have well controlled disease. Controlled disease is considered if there has been no change in medications (oral or insulin) greater than 10% for the past 30 days.
EXCLUSION CRITERIA:
1. Clinically significant unrelated systemic illness (such as serious infections requiring active systemic therapy; cardiovascular disease [congestive heart failure, recent myocardial infarction, unstable angina, inadequately controlled hypertension], poorly controlled diabetes; hepatic renal or other organ dysfunction) which would, in the judgment of the treating physician, compromise the patient's ability to tolerate the investigational agent or be likely to interfere with the study procedures or results.
2. Known hypersensitivity to any of the components of R1507 or prior hypersensitivity reactions to monoclonal antibodies.
3. Concomitant use of any other investigational agent(s). An investigational therapy is defined as treatment for which there is currently no approved indication from regulatory authorities. Prior use of investigational agent(s) is acceptable if at least 3 weeks have elapsed since last dose and no future doses are planned.
4. Treatment within the past 2 weeks with pharmacologic doses of corticosteroids [equivalent to equal 20 mg prednisone daily (or equal to 0.5 mg/kg in patients less than 10 years old)] or other immunosuppressive agents.
5. Current or prior therapy with IGF inhibitor (monoclonal or specific kinase inhibitor).
6. Pregnant patients or patients who are breast feeding. Subjects capable of pregnancy (post menarche and not post-menopausal, defined as over 12 months since final menstrual period) must have a negative pregnancy test within 7 days prior to first dose.
7. History of solid organ transplant.
8. Other malignant disease diagnosed within the previous 5 years, excluding intra-epithelial cervical neoplasia or non-melanoma skin cancer.
9. Active central nervous system disease.