| Inclusion Criteria: | 1) Patients must have histologically or cytologically confirmed one of the histologies shown below and should be stratified into one of the seven treatment cohorts defined below Ewing's sarcoma (Ewing's family of tumors, ESFT) cohorts -Primary cohort: Ewing's sarcoma primary cohort (defined as those patients who have relapsed </= 24 months from diagnosis, and received at least 2 prior chemotherapy programs (one initial and a second for 1st relapse) and are unresectable).
2) Continued from #1 - Secondary cohort: Ewing's sarcoma non-primary cohort (defined as those patients who have relapsed >/= 24 months from diagnosis or have only received only 1 prior chemotherapy program) -Expanded cohort: Patients with recurrent or relapsed Ewing's sarcoma regardless of number of prior number of salvage regimens and regardless of time to relapse. The dose and schedule of R1507 in this cohort will differ from that of all other cohorts, as will the PK, PD, safety, and HAHA assessments.
3) Continued from # 2 -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
4) Patients must have had histological verification of malignancy by central pathology review (to be completed within 6 weeks of study entry).
5) 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.
6) Age >/= 2 years. For patients enrolled in the expanded Ewing's sarcoma cohort 3 only, age must be >/= 2 and < 21 years.
7) Life expectancy of at least 6 weeks.
8) Karnofsky performance status of >/= 70%
9) 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, lesions seen on PET scan will not be considered measurable. -For patients enrolled in all cohorts with the exception of expanded Ewing's sarcoma cohort 3, lesions that are situated in a previously irradiated area will not be considered measurable. criteria will be considered measurable .
10) Continued from # 9 - For patients enrolled in the expanded Ewing's sarcoma cohort 3 only, lesions that are situated in an area of prior irradiation that have progressed and are measurable by WHO criteria will be considered measurable .
11) Adequate organ function requirements defined as: Bone marrow (in the absence of bone marrow involvement by neoplasia), Absolute neutrophil count >/= 1.5 x 10^9/L (being >/= 2 weeks off growth factors, Platelet count >/= 75,000/microliter *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.
12) Hepatic-Total bilirubin </= 1.5 times the ULN for age. ALT/AST (SGPT/SGOT) </= 3x the ULN for the reference lab( </= 5x the ULN for the reference lab in the presence of known hepatic metastasis, adjusted for age)
13) Renal-Creatinine clearance >/= 70 ml/min/1.73m2 or Serum creatinine < 1.5 x ULN per age.
14) Prior Therapy-Time elapsed from previous therapy must be >/= 3 weeks. Patients must be recovered (toxicities </= grade 1 except for alopecia) from the effects of any prior surgery, radiotherapy or systemic therapy, including any investigational therapy.
15) Patients who have undergone autologous hematopoietic stem cell transplantation (HSCT) will be eligible once they have recovered from all toxicities from therapy (</= grade 1 except for alopecia). Patients who have received allogenic 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.
16) Patients with 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 >/= 6 weeks from completion of brain irradiation.
17) 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.
18) 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.
19) 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. |