Ewing’s sarcoma and other sarcoma subtypes MedDRA version: 9.1 Level: LLT Classification code 10015560 Term: Ewing's sarcoma
Conditions
Interventions
Product Name: R1507
Product Code: RO4858696 (CHO)
Pharmaceutical Form: Powder for concentrate for solution for infusion
CAS Number: 89957-37-9
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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 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. *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 investigatorand must have documented progressive disease by WHO criteria (see Appendix B). 4. Age >2 years - For patients enrolled in the expanded Ewing’s sarcoma cohort 3 only, age must be = 2 and = 21 years. 5. Life expectancy of at least 6 weeks. 6. Karnofsky performance status of > 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, 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. (see section 11.1.1) -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 . (see section 11.1.1). 8. Adequate organ function requirements (see protocol for definition) 9. 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. - 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 allogeneic HSCT will be eligible 6 months after
Exclusion criteria
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 (refer to section 8.3 for study drug formulation). 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. 9) Active central nervous system disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To determine the overall objective response rate of R1507 in patients with recurrent or refractory osteosarcoma, synovial sarcoma, rhabdomyosarcoma and other sarcomas of the following subtypes: alveolar soft part sarcoma, desmoplastic small round cell tumor, extraskeletal myxoid chondrosarcoma, clear cell sarcoma, and myxoid liposarcoma. 2. To determine the progression-free survival at 18 weeks from start of treatment of patients with progressive, recurrent or refractory Ewing’s sarcoma (Ewing’s family of tumors) treated with R1507. 3. To determine the safety and response rate for patients with recurrent or refractory Ewing’s sarcoma/Ewing’s family of tumors regardless of prior therapy or time to progression when treated with R1507 on an every three week schedule. ; Secondary Objective: 1. To estimate the duration of response, time to progression, failure-free survival , OS, PFS rate at 18 weeks from start of treatment and overall PFS of pts with recurrent or refractory, Ewing’s sarcoma nonprimary cohort, osteosarcoma, synovial sarcoma, rhabdomyosarcoma and other sarcomas who were treated with R1507. 2. To determine the overall objective response rate, response duration, time to progression, failure-free survival, overall PFS and OS of pts with progressive, recurrent or refractory Ewing’s sarcoma/Ewing’s family of tumors primary cohort treated with R1507. 3. To define the population pharmacokinetic profile of R1507 in selected study patients. 4. To define the tolerability and adverse event profile of R1507 in sarcoma pts. ; Primary end point(s): • For Ewing’s sarcoma (primary cohort): a one-sided 97.4% confidence interval will be calculated around the 18-week progression-free survival rate. • For osteosarcoma, rhabdomyosarcoma, synovial sarcoma, Ewing’s sarcoma (non-primary cohort), expanded Ewin | — |
Countries
France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom
Outcome results
None listed