A Group Wide Biology and Banking Study for Phase II Study of R1507

Background:

• R1507 is a recombinant, fully human monoclonal IgG1 antibody that binds specifically to the human IGF-1R, resulting in direct inhibition of ligand binding and loss of receptor protein on the cell surface following intracellular internalization and degradation.
• Binding of R1507 has been shown to inhibit signal transduction and proliferation and survival functions mediated by the IGF-1R in cancer cells. Pre-clinical toxicology and safety pharmacology studies have been performed with R1507 and phase 1 studies in adults have resulted in a recommended intravenous dose of 9 mg/kg weekly. Phase 1 studies are ongoing in children.
• A Phase II study (SARC011/Roche NO21157): A Phase II Trial of R1507, a Recombinant Human Antibody to the Insulin-Like Growth Factor-1 Receptor for the treatment of patients with recurrent or refractory Ewing s sarcoma, osteosarcoma, synovial sarcoma, rhabdomyosarcoma and other sarcomas will allow an opportunity to collect tumor tissue and serum samples to further characterize the biology of sarcomas and their response to IGF1-R monoclonal antibody therapy.

Objectives:

• To analyze tumor tissue for IGF-1R, phosphor (p)-IGF-1R, Akt, p-Akt, PTEN, and other candidate markers related to the mechanism of action of R1507 in the treatment of patients with sarcoma and other solid tumors.
• To determine whether specific tissue-based assays performed on diagnostic specimens will allow for the identification of newer prognostic categories and potentially new molecular targets for treatment of patients with sarcoma and other solid tumors.
• To determine whether serum levels of free IGF-I/II, total IGF-I and shed IGF-1R are of significance in the outcome of patients with sarcoma and other solid tumors.
• To identify new treatment targets for therapy. Further testing of these potential targets will be carried out in hopes of expediting translation of these findings to the clinical setting.

Eligibility: