A Phase II Trial of Avelumab in Patients With Recurrent or Progressive Osteosarcoma
Condition: Osteosarcoma
MeSH terms: Osteosarcoma
Study type: Interventional
Phase: Phase 2

Summary: 
      This clinical trial seeks to determine if avelumab will be effective in facilitating removal
      of all gross tumor in the event of a relapse of osteosarcoma in pediatric patients. Avelumab
      will be evaluated using dosing that has previously been determined in adult studies.

      Primary Objectives:

        -  To estimate the response rate to 4 cycles of avelumab in patients with recurrent or
           progressive osteosarcoma.

        -  To estimate the 16-week progression free survival of patients with recurrent or
           progressive osteosarcoma after treatment with avelumab.

      Secondary Objective:

        -  To describe the toxicities associated with the administration of avelumab in patients
           with recurrent or progressive osteosarcoma.

        -  To assess the quality of life of patients with recurrent or progressive osteosarcoma
           undergoing treatment with avelumab, and to explore relationships between clinical
           factors and patient-reported health-related quality of life (HRQOL) outcomes.

      Exploratory Objectives:

        -  To explore factors associated with response in patients treated with avelumab after
           recurrent or progressive osteosarcoma (e.g. tumor PD-L1 expression).

        -  To measure parameters of immune activation including subsets of peripheral blood
           mononuclear cells (PBMCs) and serum markers of immune activation.

        -  To evaluate the role of T-cells in immune checkpoint blockade via measures of cell
           proliferation, co-inhibitory receptor expression on CD8 T cells, T cell repertoire, and
           epigenetic programming.
    

Detailed description: 
      This is a Phase 2 study using a traditional Simon two-stage design. Patients 12 years or
      greater with recurrent/refractory osteosarcoma will be administered avelumab at a dose of 10
      mg/kg intravenously (IV) over 60 minutes on days 1 and 15 of each cycle, with a cycle lasting
      28 days.

      Patients will receive avelumab every 2 weeks in cycles of 28 days for up to 24 months, or 26
      cycles. Progression free survival and response to therapy after 4 cycles of treatment will be
      assessed. In addition, the toxicity profile of avelumab in this population will be closely
      monitored.
    

Intervention name(s): Avelumab; Questionnaires
Intervention type(s): Drug; Other
Intervention description(s): Patients will be administered avelumab at a dose of 10 mg/kg intravenously (IV) over 60 minutes on days 1 and 15 of each cycle, with a cycle lasting 28 days. Patients will receive avelumab every 2 weeks in cycles of 28 days for up to 24 months, or 26 cycles.; To assess quality of life, patients will complete questionnaires at four time points.
Other intervention name(s): MSB0010718C; anti-PD-L1; PROMIS Pediatric Profile; PROMIS Adult Profile
Intervention MeSH terms: Avelumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Osteosarcoma; PD-L1; Immunotherapy