This phase I trial studies the side effects and the best dose of wild-type reovirus (viral therapy) when given with sargramostim in treating younger patients with high grade brain tumors that have come back or that have not responded to standard therapy. A virus, called wild-type reovirus, which has been changed in a certain way, may be able to kill tumor cells without damaging normal cells. Sargramostim may increase the production of blood cells and may promote the tumor cell killing effects of wild-type reovirus. Giving wild-type reovirus together with sargramostim may kill more tumor cells.
PRIMARY OBJECTIVES: I. To define the maximum tolerated dose (MTD) and describe the toxicities of wild-type reovirus (Reolysin) when given once a day for three days following two days of treatment with sargramostim (GM-CSF). SECONDARY OBJECTIVES: I. To assess the safety, tolerability and adverse events in the patient population. II. To assess the median overall survival time in this patient population. III. To assess the median progression free survival time in this patient population. TERTIARY OBJECTIVES: I. To determine whether there is a correlation between antibody responsiveness to the virus and a positive tumor response to Reolysin in patients who receive the virus following treatment with GM-CSF. II. To determine whether there is a correlation between an increased number of circulating monocytes and a positive tumor response to Reolysin in patients who receive the virus following treatment with GM-CSF. III. To explore the possible predictive value of monocyte numbers in response to Reolysin + GM-CSF therapy. OUTLINE: This is a dose-escalation study of wild-type reovirus. Patients receive sargramostim subcutaneously (SC) daily on days 1 and 2 and wild-type reovirus intravenously (IV) over 60 minutes on days 3-5. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Mayo Clinic
Rochester, Minnesota, United States
MTD, based on the incidence of dose-limiting toxicity (DLT) assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0
MTD is the highest safely tolerated dose level where 1 of 6 patients experience DLT with the next higher dose having at least 2 patients out of a maximum of 6 patients experience DLT.
Time frame: Up to 84 days
Adverse event profile
The number and severity of adverse events (overall, by dose level, by treatment received) will be tabulated and summarized. The grade 3+ adverse events will also be described and summarized in a similar fashion.
Time frame: Up to 5 years
Objective responses
Objective responses will be summarized by descriptive summary statistics delineating complete and partial responses and stable and progressive disease.
Time frame: Up to 5 years
Overall survival
Will be summarized descriptively. Simple summary statistics will be supplemented with Kaplan-Meier survival estimates and relevant confidence intervals.
Time frame: Up to 5 years
Time to progression
Up to 5 years
Time frame: Will be summarized descriptively.
Time to treatment failure
Will be summarized descriptively. Time to treatment failure is defined as the time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient.
Time frame: Up to 5 years
Time until any treatment-related toxicity
Will be summarized descriptively.
Time frame: Up to 5 years
Time until treatment-related grade 3+ toxicity
Will be summarized descriptively.
Time frame: Up to 5 years
Toxicity profile, assessed by CTCAE v4.0
Toxicity is defined as adverse events that are classified as possibly, probably, or definitely related to study treatment. Overall toxicity incidence and toxicity profiles by dose level, patient, and treatment will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of the analysis.
Time frame: Up to 5 years
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