RATIONALE: Oncolytic viruses such as reovirus (REOLYSIN®) can specifically kill tumor cells while leaving healthy cells unharmed. PURPOSE: This phase I/II study investigates the maximum tolerated dose (MTD), dose limiting toxicity (DLT) and anti-tumor effect of intralesional administration of REOLYSIN® therapeutic reovirus in patients with malignant glioma with evaluable disease which is progressive/recurrent despite surgery and/or radiotherapy with or without chemotherapy. (The phase I portion of the study is currently enrolling patients.)
Oncolytic viruses, such as reovirus, are those viruses which specifically destroy cancer cells. Reovirus is a common virus that does not cause disease, and has been shown to be associated with only minor flu-like symptoms. REOLYSIN® is a formulation of the live, replication-competent wild-type reovirus that selectively replicates in tumor cells, while leaving healthy cells unharmed. This phase I/II multi-center study follows a standard design utilizing therapeutic viral dosage escalation. The phase I portion of the trial will evaluate the doses of intralesional REOLYSIN titrated to a maximum tolerated dose (MTD). The objective of the phase II portion of the study is to assess tumor response. The proportion of patients surviving to six months and the safety of REOLYSIN® are secondary objectives. Each patient enrolled in the study will receive a single infusion of REOLYSIN® over 72 hours. Patients will remain in hospital for at least 90 hours after initiation of infusion. Following REOLYSIN® administration, each patient will be followed for at least 12 weeks (Phase I) and at least 6 months (Phase II) with regular evaluation visits (weekly and then monthly). Evaluations will include tumor measurements, serial neurologic exams and functional performance status assessments at baseline, prior to hospital discharge, and at weeks 4, 8, 12, 16 and 24 after REOLYSIN® therapy. Changes in performance will be assessed using the Karnofsky Performance Status scale. Subjects will also undergo serial blood sampling for evaluation of viral RNA, hematology and biochemistry.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
REOLYSIN® is administered as a single intratumoral infusion over 72 hours. Dose levels in Phase 1 will be 1x10E8, 3x10E8, 1x10E9, 3x10E9, 1x10E10 TCID50. The dose level for Phase 2 will be the top dose reached in Phase 1.
University of Alabama at Birmingham
Birmingham, Alabama, United States
Cedars-Sinai Medical Center
Los Angeles, California, United States
The Ohio State University Medical Center and Arthur G. James Cancer Hospital and Richard J. Solove Research Center
Columbus, Ohio, United States
determine the maximum tolerated dose
Time frame: in the first 28 days following REOLYSIN® administration
and response rate of treated tumors
Time frame: evaluated monthly for 6 months following REOLYSIN® administration
determine the dose limiting toxicity
Time frame: in the first 28 days following REOLYSIN® administration
Determine the patient survival
Time frame: patients are in follow up for up to six months
functional status using the Karnofsky Performance Status scale and Clinical Neurological Assessment
Time frame: evaluated monthly for up to 6 months
time to progression for the treated tumor
Time frame: evaluated monthly for up to 6 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
NONE
Enrollment
18