Safety and Efficacy Study of REOLYSIN® in the Treatment of Bone and Soft Tissue Sarcomas Metastatic to the Lung

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Oncolytics Biotech
ClinicalTrials.gov Identifier:
NCT00503295
First received: July 16, 2007
Last updated: May 1, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Osteosarcoma
Ewing Sarcoma Family Tumors
Malignant Fibrous Histiocytoma
Sarcoma, Synovial
Fibrosarcoma
Leiomyosarcoma
Biological: REOLYSIN®
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Oncolytics Biotech:

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. [ 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. ] [ Designated as safety issue: No ]

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®. [ Time Frame: within 30 days of the last dose of REOLYSIN® ] [ Designated as safety issue: Yes ]

Enrollment: 53
Study Start Date: June 2007
Study Completion Date: April 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: REOLYSIN®
    REOLYSIN® is given intravenously at a dose of 3x10E10 TCID50 over 60 minutes on Days 1-5 of a 28 day cycle.
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:

  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®.
  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00503295

Locations
United States, Michigan
University of Michigan Medical School
Ann Arbor, Michigan, United States, 48106
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Montefiore Medical Center/Albert Einstein College of Medicine
Bronx, New York, United States, 10461
United States, Texas
Institute of Drug Development, Cancer Therapy Research Center
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Oncolytics Biotech
Investigators
Study Director: Karl Mettinger, MD, PhD Oncolytics Biotech
  More Information

Additional Information:
No publications provided

Responsible Party: Oncolytics Biotech
ClinicalTrials.gov Identifier: NCT00503295     History of Changes
Other Study ID Numbers: REO 014
Study First Received: July 16, 2007
Last Updated: May 1, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Oncolytics Biotech:
reovirus
oncolytic virus
sarcoma
REOLYSIN
Oncolytics Biotech

Additional relevant MeSH terms:
Histiocytoma
Fibrosarcoma
Leiomyosarcoma
Osteosarcoma
Sarcoma, Synovial
Histiocytoma, Benign Fibrous
Histiocytoma, Malignant Fibrous
Sarcoma, Ewing
Sarcoma
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Muscle Tissue
Neoplasms, Bone Tissue

ClinicalTrials.gov processed this record on August 28, 2014