The purpose of this study is to determine if the investigational products, DB107-RRV and DB107-FC, as a combination treatment will shrink high-grade glioma (HGG) in patients with recurrent/progressive, resectable or unresectable disease and increase the time that disease is controlled.
Patients 18-75 years old.
Histologically proven HGG that have recurred/progressed (first or second recurrence).
Patients with unresectable or resectable HGG (AA or GBM) will be enrolled.
Measurable disease on MRI as evidenced by 1 cm on two separate dimensions on MRI fluid attenuated inversion recovery (FLAIR) (non-enhancing) or contrast-enhancement.
History of active other malignancy (other than non-melanoma skin cancers, cervical ductal carcinoma in situ or localized prostate cancer) within 5 years.
Multifocal gliomas that cannot undergo stereotactic biopsy/administration of DB107-RRV will be excluded. Patients with 3 or more intracranial recurrences will be excluded.
Histologically confirmed oligodendroglioma or mixed gliomas.
History of human immunodeficiency virus (HIV) infection or other forms of severe immunosuppression.
Single group
DB107-RRV
DrugPatients will undergo surgery to remove as much of the high-grade glioma (HHG) tumor as possible and will receive combination intravenous (IV) and adaptive repeat intratumoral delivery of DB107-RRV in the vein (IV) and in the walls of the cavity that remains where tumor is removed.
DB107-FC
DrugPatients will start taking DB107-FC three times by mouth every day for a period of seven days, which is one cycle of treatment. A cycle of treatment is medication taken on a set schedule with periods of rest in between. Patients will wait five weeks before taking the next seven day course of DB107-FC. The first dose of DB107-FC will be taken at the hospital or clinic; afterward, patients will take the doses of DB107-FC at home. Patients will take DB107-FC for up to 12 months after surgery.
Progression Free Survival
Progression free survival (PFS) is defined as duration from initiation of treatment to the point of disease progression or death.
Overall Survival
Overall survival (OS) refers to the duration from the initiation of enrollment until death, regardless of the cause.
Assessment of Tumor Status Measured by Response Assessment in Neuro-oncology (RANO) Criteria
To evaluate the radiological response in participants with recurrent HGG based on overall response (CR) or partial response (PR), stable disease (SD), and progressive disease (PD) per the Response Assessment in Neuro-oncology (RANO) criteria.
Number of Treatment Related Toxicities
Number of treatment related toxicities will be assessed by the development of treatment-related ≥ Grade 3 adverse events as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Durable Response Rate (DRR)
Durable response rate (DRR) is defined as the proportion of patients whose best response to treatment is either complete response (CR) or partial response (PR) lasting at least 24 weeks as evidenced by MRI. DDR is calculated as the total number of patients with CR or PR lasting at least 24 weeks.
Durable Clinical Benefit Rate (DCBR)
Durable clinical benefit rate (DCBR) is defined as the proportion of patients whose best overall response is either CR or PR lasting at least 24 weeks or SD lasting at least 12 months according to modified RANO criteria as evidenced by MRI imaging. Durable clinical benefit rate is calculated as the total number of patients with CR or PR ≥ 24 weeks or with SD \> 12 months.
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Ashish Shah
Lead sponsor
University of Miami
Sponsor institution
Denovo Biopharma LLC
Collaborator
National Cancer Institute (NCI)
Collaborator
