INCLUSION CRITERIA:
1. Patients must have histologically or cytologically confirmed
-Ewing's sarcoma (Ewing's family of tumors, ESFT)
-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. For the patients with Ewing's and ESFT subtype, patients must have documented progressive disease by WHO criteria.
4. Age greater than or equal to 12 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:
8a. 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 30 days off growth factors.
2. Platelet count greater than or equal to 75,000/mL.
Note: in patients with documented 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 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. There should be no sign or symptom of ketosis at enrollment or within 30 days prior to enrollment.
13. The ESFT population for whom the time from diagnosis to first relapse is less than or equal to 24 months, patients must have received at least two distinct chemotherapy programs (one for initial systemic therapy and a second for first relapse) and be surgically unresectable.
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. Current or previous treatment (within the past 6 months) with chronic, pharmacologic doses of corticosteroids, immunosuppressive agents or medications that inactivate or may interfere with the pharmacologic activity of R1507.
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.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 09/16/2008