A Phase 2 Study of Intravenous REOLYSIN® (Wild-Type Reovirus) in the Treatment of Patients With Bone and Soft Tissue Sarcomas Metastatic to the Lung
Sarcomas are uncommon mesenchymal malignancies that encompass a variety of tumors of soft
tissue or bone. Included in this study are patients with osteosarcoma, Ewing sarcoma family
tumors, malignant fibrous histiocytoma, synovial sarcoma, leiomyosarcoma and fibrosarcoma.
Patients with these lesions presenting with metastatic disease remain largely incurable. In
all sarcomas, the lungs are by far the most frequent site of metastases.
There is a need for new therapies that have activity against these types of sarcomas.
REOLYSIN® is an unmodified oncolytic reovirus which replicates selectively in ras
transformed cells causing cell lysis. Activating mutations in ras or mutations in oncogenes
signaling through the ras pathway may occur in as many as 80% of human tumors. Such
mutations have been described in many of the common sarcomas of childhood and adults.
REOLYSIN® demonstrated excellent anti-tumor activity in vitro and in vivo in childhood
sarcoma cell lines.
Further supporting the development of REOLYSIN® in the context of sarcomas as detailed in
this study, is the fact that sarcomas resistant or refractory to conventional chemotherapy
may remain clinically responsive to viral therapy. Sarcoma patients with pulmonary
metastases may be especially suitable for studies with REOLYSIN® due to rapid selective
uptake of the virus by the lungs.
This Phase 2 study is designed to characterize the efficacy and safety of REOLYSIN® given
intravenously over 5 days every 4 weeks in patients with bone and soft tissue sarcomas
metastatic to the lung. Safety data, including laboratory parameters and adverse events,
will be collected for all patients in order to determine the toxicity and reversibility of
toxicity of REOLYSIN® therapy. Response will be assessed using radiographic imaging every 2
cycles of therapy.
1. To measure tumor responses and duration of response, and describe any evidence of
antitumor activity of intravenous multiple dose REOLYSIN® in patients with bone and
soft tissue sarcomas metastatic to the lung.
2. To evaluate safety of intravenous multiple dose REOLYSIN®.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Complete response (CR) and partial response (PR) as well as prolonged stabilization of disease (SD) will be considered indicative of response. RECIST criteria will be utilized to assess radiographic response.
For PR or CR, changes in tumor measurements must be confirmed 4 weeks after the criteria for response are first met. For SD, follow-up measurements must have met the SD criteria at least once after trial entry at a minimum interval of 12 weeks.
Karl Mettinger, MD, PhD
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|
|University of Michigan Medical School||Ann Arbor, Michigan 48106|
|Montefiore Medical Center/Albert Einstein College of Medicine||Bronx, New York 10461|
|Institute of Drug Development, Cancer Therapy Research Center||San Antonio, Texas 78229|