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

Sponsor

Oncolytics Biotech (Industry)

Overall Status

Completed

CT.gov ID

NCT00503295

Collaborator

(none)

Enrollment

Locations

Duration (Months)

13.3

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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.

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

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®.

Study Design

Study Type:

Interventional

Actual Enrollment :

53 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Jun 1, 2007

Actual Primary Completion Date :

Feb 1, 2011

Actual Study Completion Date :

Apr 1, 2011

Outcome Measures

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. [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 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®. [within 30 days of the last dose of REOLYSIN®]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Medical School	Ann Arbor	Michigan	United States	48106
2	Mayo Clinic	Rochester	Minnesota	United States	55905
3	Montefiore Medical Center/Albert Einstein College of Medicine	Bronx	New York	United States	10461
4	Institute of Drug Development, Cancer Therapy Research Center	San Antonio	Texas	United States	78229