Wild-Type Reovirus in Combination With Sargramostim in Treating Younger Patients With High-Grade Relapsed or Refractory Brain Tumors
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02444546|
Recruitment Status : Recruiting
First Posted : May 14, 2015
Last Update Posted : March 19, 2018
|Condition or disease||Intervention/treatment||Phase|
|Childhood Astrocytoma Childhood Atypical Teratoid/Rhabdoid Tumor Diffuse Intrinsic Pontine Glioma Glioma Recurrent Childhood Anaplastic Oligodendroglioma Recurrent Childhood Brain Neoplasm Recurrent Childhood Glioblastoma Recurrent Childhood Medulloblastoma Recurrent Primitive Neuroectodermal Tumor Refractory Brain Neoplasm||Other: Laboratory Biomarker Analysis Biological: Sargramostim Biological: Wild-type Reovirus||Phase 1|
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).
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.
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 (Clinical Trial)|
|Estimated Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1 Study of Replication Competent Reovirus (Reolysin®) in Combination With GM-CSF in Pediatric Patients With Relapsed or Refractory Brain Tumors|
|Actual Study Start Date :||June 2015|
|Estimated Primary Completion Date :||April 2020|
|Estimated Study Completion Date :||April 2020|
Experimental: Treatment (sargramostim, wild-type reovirus)
Patients receive sargramostim SC daily on days 1 and 2 and wild-type reovirus 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.
Other: Laboratory Biomarker Analysis
Biological: Wild-type Reovirus
Other Name: Reolysin
- MTD, based on the incidence of dose-limiting toxicity (DLT) assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 [ Time Frame: Up to 84 days ]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.
- Adverse event profile [ Time Frame: Up to 5 years ]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.
- Objective responses [ Time Frame: Up to 5 years ]Objective responses will be summarized by descriptive summary statistics delineating complete and partial responses and stable and progressive disease.
- Overall survival [ Time Frame: Up to 5 years ]Will be summarized descriptively. Simple summary statistics will be supplemented with Kaplan-Meier survival estimates and relevant confidence intervals.
- Time to progression [ Time Frame: Will be summarized descriptively. ]Up to 5 years
- Time to treatment failure [ Time Frame: Up to 5 years ]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 until any treatment-related toxicity [ Time Frame: Up to 5 years ]Will be summarized descriptively.
- Time until treatment-related grade 3+ toxicity [ Time Frame: Up to 5 years ]Will be summarized descriptively.
- Toxicity profile, assessed by CTCAE v4.0 [ Time Frame: Up to 5 years ]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.
- Immunologic parameters [ Time Frame: Up to 5 years ]For each of the immunologic parameters, a time series plot will be constructed. A grid reflecting the percent change from pre-treatment levels will be constructed. This grid will be analyzed to determine if the changes seen in each immunologic parameter differ between patients who response and those which do not respond.
- Reovirus immune status [ Time Frame: Up to 5 years ]The reovirus immune status will be correlated with objective response to analyze if the status is predictive of sargramostim plus wild-type reovirus therapy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02444546
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Clinical Trials Referral Office 855-776-0015|
|Principal Investigator: Richard J. Bram|
|Principal Investigator:||Richard Bram||Mayo Clinic|