A Phase 1 Study of Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) (NSC 729968) in Patients With Ovarian, Primary Peritoneal and Fallopian Tube Carcinoma
I. Determine the safety and tolerability of intravenous (IV) and intraperitoneal (IP)
administration of wild-type reovirus (REOLYSIN®).
II. Determine the maximum tolerated dose of IP REOLYSIN® when used with a fixed dose of IV
III. Determine the objective response rate (complete response and partial response per
Response Evaluation Criteria in Solid Tumors [RECIST] criteria) of treatment with IV and IP
REOLYSIN® in patients with recurrent, platinum-refractory ovarian epithelial, peritoneal, or
fallopian tube carcinoma. (Phase II) (phase II closed as of 1/7/2011).
I. To identify viral replication in tumor following IV reovirus. II. To identify
anti-reovirus antibodies in patients being treated with IV and IP REOLYSIN® therapy.
III. To identify viral replication in the abdominal washings of patients undergoing IV and
IP REOLYSIN® therapy.
IV. To correlate response to therapy with Ras oncogene status. V. To evaluate
double-stranded RNA-activated protein kinase activity in tumors. VI. To correlate molecular
predictors of response to REOLYSIN® therapy.
OUTLINE: This is a phase I, dose-escalation study of intraperitoneal (IP) wild-type reovirus
when administered with fixed dose IV wild-type reovirus.
PHASE I: Patients receive wild-type reovirus IV over 60 minutes on days 1-5 in course 1,
followed by insertion of an IP access port. Beginning in course 2, patients receive
wild-type reovirus IV over 60 minutes on days 1-5 and wild-type reovirus IP over 10 minutes
on days 1 and 2*. Treatment with IV and IP wild-type reovirus repeats every 28 days in the
absence of disease progression or unacceptable toxicity.
PHASE II: Patients undergo IP access port insertion before beginning treatment. Patients
receive wild-type reovirus IV over 60 minutes on days 1-5 and IP (at the maximum tolerated
dose determined in phase I) over 10 minutes on days 1 and 2*. Treatment repeats every 28
days in the absence of disease progression or unacceptable toxicity (phase II closed as of
1/7/2011). NOTE: *Patients receive IP wild-type reovirus on days 2 and 3 in course 3.
Prior to each IP wild-type reovirus administration, normal saline is administered through
the IP catheter and withdrawn for correlative studies in courses 2 and 3 (phase I) or
courses 1 and 2 (phase II). Patients also undergo a CT-guided percutaneous tumor biopsy on
day 2 of course 3 (phase I or II). Samples are analyzed by immunohistochemistry, RT-PCR, and
electron microscopy for the relevant molecular effects of wild-type reovirus on tumor and
After completion of study treatment, patients are followed for up to 12 weeks.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerable dose of intraperitoneal (IP) wild-type reovirus when administered with fixed dose IV wild-type reovirus (phase I)
Dose-limiting toxicity will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v. 4
At each dose level, assessed up to 5 dose levels
Ohio State University
United States: Food and Drug Administration
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