Blood and Tissue Study of Patients in NIH Protocol 08-C-0800
Condition: Sarcomas
MeSH terms: Sarcoma
Study type: Observational

Summary: 
      Background:

        -  This study is a companion biology study to NIH protocol 08-C-0080, 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.

        -  Analysis of tumor tissue and blood samples from patients with sarcomas who are receiving
           treatment with the experimental drug R1507 may help elucidate the biology of sarcomas
           and how they respond to certain therapies with monoclonal antibodies.

      Objectives:

        -  To study the effect over time of R1507 on the proteins and cells in the blood and tissue
           of patients with sarcoma in order to learn more about how patients respond to the
           treatment and what changes occur in their cells.

        -  To discover possible new treatments for cancer.

      Eligibility:

        -  Participants in NIH protocol 08-C-0080 for the study of R1507 to treat people with
           various sarcomas.

      Design:

        -  Patients who previously agreed as part of protocol 08-C-0800 to have blood sampling for
           pharmacodynamic studies (blood draws to test blood for levels of R1507 and how the body
           affects R1507) will not have any additional blood drawn as part of this study.

        -  Patients who did not previously agree to pharmacodynamic sampling as part of the
           protocol 08-C-0800 will be asked to give 6 blood samples at various time periods during
           the study.

        -  Pathology slides or tissue blocks obtained under protocol 08-C-0800 will be forwarded to
           F. Hoffmann-La Roche laboratories for analysis.
    

Detailed description: 
      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:

      -All patients enrolled on the Phase II study SARC011/Roche NO21157 will be eligible for
      enrollment.

      Design:

        -  Unstained tumor tissue slides from samples sent for confirmatory diagnosis will be
           forwarded for further analysis from Central Pathology Labs in New York or Leiden to
           Roche Clinical Sample Operations (CSO). Tissue based assays to evaluate the status of
           IGF-1R downstream pathway will be performed by Roche Central Lab (HistoGeneX) and NCI
           Lab.

        -  Serum based assays of free serum IGF-I/II, total serum IGF-I and shed IGF-1R receptor
           will be run using the samples obtained prior to the first dose of R1507 and at specified
           times during treatment as described in Table 3.3. All serum samples will be shipped to
           the Roche CSO and forwarded for analysis to the designated laboratories. Serum based
           assays will be performed by Roche Central Lab (MicroCoat) and Roche Diagnostics
           (Penzberg).
    

Observational model: Case-Only
Time perspective: Prospective
Keywords: Biomarker Analysis; Sarcomas; Ewing's Sarcoma; Osteosarcoma; Rhabdomyosarcoma; Synovial Sarcoma; Other Sarcoma