Safety and Efficacy Study of REOLYSIN® in the Treatment of Bone and Soft Tissue Sarcomas Metastatic to the Lung
Primary Purpose
Osteosarcoma, Ewing Sarcoma Family Tumors, Malignant Fibrous Histiocytoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
REOLYSIN®
Sponsored by
About this trial
This is an interventional treatment trial for Osteosarcoma focused on measuring reovirus, oncolytic virus, sarcoma, REOLYSIN, Oncolytics Biotech
Eligibility Criteria
Inclusion Criteria:
- have a bone or soft tissue sarcoma metastatic to the lung deemed by a physician to be unresponsive to, or untreatable by, standard therapies. Acceptable histologies include only osteosarcoma, Ewing sarcoma family tumors, malignant fibrous histiocytoma, synovial sarcoma, fibrosarcoma and leiomyosarcoma
- have ≥ 2 measurable lesions in the lungs detectable on CT scan
- all residual adverse effects related to any prior anti-cancer therapy including, but not limited to, chemotherapy, biologic therapy, radiotherapy or surgical procedures must have resolved to Grade 1 or lower (as defined by the Common Terminology Criteria for Adverse Events, Version 3.0) before study therapy is initiated
- have received NO chemotherapy, radiotherapy, immunotherapy, hormonotherapy or surgery (except skin surgeries and minor biopsies) within 28 days prior to receiving REOLYSIN®
- have ECOG Performance Score of ≤ 2
- have life expectancy of at least 3 months
- Absolute neutrophils ≥ 1.5 x10^9/L; hemoglobin ≥ 9.0g/dL; platelets ≥ 100 x 10^9/L
- SGOT/SGPT (AST/ALT) ≤ 2.5 x ULN; bilirubin ≤ 1.5 x ULN
- Serum creatinine ≤ 1.5 x ULN
- negative pregnancy test for females of childbearing potential
Exclusion Criteria:
- have inadequate pulmonary function defined as a forced expiratory volume in 1 second (FEV1) less than 50% of predicted
- be on immunosuppressive therapy; have known HIV infection or active hepatitis B or C
- have clinically significant pulmonary or cardiac disease
- have dementia or altered mental status that would prohibit informed consent
- have any other severe or acute chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgement of the Principal Investigator, would make the patient inappropriate for this study
Sites / Locations
- University of Michigan Medical School
- Mayo Clinic
- Montefiore Medical Center/Albert Einstein College of Medicine
- Institute of Drug Development, Cancer Therapy Research Center
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Safety data, including laboratory parameters and adverse events, will be collected for all patients in order to determine the qualitative and quantitative toxicity, and reversibility of toxicity, of REOLYSIN®.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00503295
Brief Title
Safety and Efficacy Study of REOLYSIN® in the Treatment of Bone and Soft Tissue Sarcomas Metastatic to the Lung
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2012
Overall Recruitment Status
Completed
Study Start Date
June 2007 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
April 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Oncolytics Biotech
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this Phase 2 study is to investigate whether intravenous administration of REOLYSIN® therapeutic reovirus is safe and effective in the treatment of patients with bone and soft tissue sarcomas metastatic to the lung.
Detailed Description
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.
OBJECTIVES:
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.
To evaluate safety of intravenous multiple dose REOLYSIN®.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteosarcoma, Ewing Sarcoma Family Tumors, Malignant Fibrous Histiocytoma, Sarcoma, Synovial, Fibrosarcoma, Leiomyosarcoma
Keywords
reovirus, oncolytic virus, sarcoma, REOLYSIN, Oncolytics Biotech
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
53 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Biological
Intervention Name(s)
REOLYSIN®
Intervention Description
REOLYSIN® is given intravenously at a dose of 3x10E10 TCID50 over 60 minutes on Days 1-5 of a 28 day cycle.
Primary Outcome Measure Information:
Title
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.
Time Frame
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.
Secondary Outcome Measure Information:
Title
Safety data, including laboratory parameters and adverse events, will be collected for all patients in order to determine the qualitative and quantitative toxicity, and reversibility of toxicity, of REOLYSIN®.
Time Frame
within 30 days of the last dose of REOLYSIN®
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
have a bone or soft tissue sarcoma metastatic to the lung deemed by a physician to be unresponsive to, or untreatable by, standard therapies. Acceptable histologies include only osteosarcoma, Ewing sarcoma family tumors, malignant fibrous histiocytoma, synovial sarcoma, fibrosarcoma and leiomyosarcoma
have ≥ 2 measurable lesions in the lungs detectable on CT scan
all residual adverse effects related to any prior anti-cancer therapy including, but not limited to, chemotherapy, biologic therapy, radiotherapy or surgical procedures must have resolved to Grade 1 or lower (as defined by the Common Terminology Criteria for Adverse Events, Version 3.0) before study therapy is initiated
have received NO chemotherapy, radiotherapy, immunotherapy, hormonotherapy or surgery (except skin surgeries and minor biopsies) within 28 days prior to receiving REOLYSIN®
have ECOG Performance Score of ≤ 2
have life expectancy of at least 3 months
Absolute neutrophils ≥ 1.5 x10^9/L; hemoglobin ≥ 9.0g/dL; platelets ≥ 100 x 10^9/L
SGOT/SGPT (AST/ALT) ≤ 2.5 x ULN; bilirubin ≤ 1.5 x ULN
Serum creatinine ≤ 1.5 x ULN
negative pregnancy test for females of childbearing potential
Exclusion Criteria:
have inadequate pulmonary function defined as a forced expiratory volume in 1 second (FEV1) less than 50% of predicted
be on immunosuppressive therapy; have known HIV infection or active hepatitis B or C
have clinically significant pulmonary or cardiac disease
have dementia or altered mental status that would prohibit informed consent
have any other severe or acute chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgement of the Principal Investigator, would make the patient inappropriate for this study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karl Mettinger, MD, PhD
Organizational Affiliation
Oncolytics Biotech
Official's Role
Study Director
Facility Information:
Facility Name
University of Michigan Medical School
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Montefiore Medical Center/Albert Einstein College of Medicine
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Institute of Drug Development, Cancer Therapy Research Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy Study of REOLYSIN® in the Treatment of Bone and Soft Tissue Sarcomas Metastatic to the Lung
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