DB107-RRV, DB107-FC, and Radiation Therapy With or Without Temozolomide (TMZ) for High Grade Glioma
A Phase I/IIa Study to Evaluate the Efficacy of DB107-RRV (Formerly Toca511), Administered to Subjects at Time of Resection and Intravenously Thereafter, in Combination With DB107-FC (Formerly Toca FC) and Radiation Therapy or DB107-FC, Temozolomide (TMZ) and Radiation Therapy in Patients With Newly Diagnosed High Grade Glioma
4 other identifiers
interventional
70
1 country
5
Brief Summary
This is a multicenter, open-label study of DB107-RRV (formerly Toca 511) and DB107-FC (formerly Toca FC) when administered following surgical resection in newly diagnosed High Grade Glioma (HGG) patients. The study is designed to evaluate whether treatment with DB107-RRV in combination with DB107-FC when added to standard of care provides clinical benefit to newly diagnosed HGG when compared to historical performance previously determined in well controlled clinical trials published in the peer reviewed literature. This study is going to be conducted in newly diagnosed HGG patients receiving with maximum surgical resection treatment followed by radiation and temozolomide treatment using the established Stupp Protocol for O6-methylguanine-DNA methyl-transferase (MGMT) methylated patients or radiation therapy for MGMT unmethylated patients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2025
Longer than P75 for phase_1
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 9, 2024
CompletedFirst Posted
Study publicly available on registry
July 16, 2024
CompletedStudy Start
First participant enrolled
January 8, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 31, 2042
March 11, 2026
March 1, 2026
3.1 years
July 9, 2024
March 9, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Proportion of participants with dose limiting toxicities (Phase I)
Tolerability is defined as the proportion of participants receiving at least one dose of DB107-RRV and DB107-FC with a reported dose-limiting toxicity for all participants in Phase I.
Up to 1 year
Proportion of participants with treatment-emergent adverse events (Phase I)
Safety is defined as the proportion of participants with treatment-emergent adverse events as classified by the Medical Dictionary for Regulatory Activities (MEDDRA) preferred terms and graded for severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for participants in Phase 1.
Up to 3 years
Median Progression free survival (PFS) by biomarker status (Phase IIa)
PFS is defined as time from first receipt of DB107-RRV until progression or death, whichever occurs first for newly diagnosed HGG patients with unmethylated MGMT and methylated MGMT. Participants without an event will be censored at the last disease assessment. PFS (months) = (earlier date of documentation of progression of disease or death/censored - date of first dose of DB107-RRV+1) (365.25/12) using Immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria to determine disease status. The median and the 95% confidence interval will be estimated using the Kaplan-Meier method.
Up to 3 years
Secondary Outcomes (6)
Recommended Phase 2 Dose (RP2D) (Phase I)
Up to 1 year
Overall Response Rate (ORR) (Phase IIa)
Up to 5 years
Median Progression-free survival (PFS) at 6 months (Phase IIa)
Up to 6 months
Median Progression-free survival (PFS) (Phase IIa)
6 months
Median Overall Survival (OS) at 6 months (Phase IIa)
6 months
- +1 more secondary outcomes
Study Arms (2)
No MGMT Methylation (DB107-RRV, DB107-FC, Radiation therapy)
EXPERIMENTALParticipants receive a 4.0 x 10\^8 transduction units per milliliter (TU/mL)) dose of DB107-RRV intracranially (IC) at resection and a 1.4 x 10\^9 TU/mL dose IV prior to leaving surgery room. Participants have up to 6 weeks for surgical recovery. Unmethylated MGMT participants receive 300 mg/kg/day DB107-FC PO during RT over 5 days during weeks 1-2, \& 5-6. 2 gray (Gy)/day standard of care (SOC) RT will be given for 5 consecutive days for 6 weeks. After RT, participants receive 1.4 x 10\^9 TU/mL of DB107-RRV IV on days 7 and 14 and continue during a 4-week rest period between RT and adjuvant therapy. Participants who begin adjuvant therapy receive 300 mg/kg/day DB107-FC PO on days 1-5 of a 28-day cycle up to 6 cycles or until PD. Participants with no PD during adjuvant treatment may receive additional cycles of DB107-FC until PD, withdrawal, death or study closure. Participants will be followed up for safety and survival status for up to 15 years.
Low to High MGMT Methylation (DB107-RRV, DB107-FC, Temozolomide (TMZ), Radiation therapy)
EXPERIMENTALParticipants receive a 4.0 x 10\^8 TU/mL dose of DB107-RRV IC at resection and a 1.4 x 10\^9 TU/mL dose IV prior to prior to leaving surgery room. Participants have up to 6 weeks for surgical recovery. Low to high MGMT methylation participants receive 75 mg/m\^2 TMZ per SOC and 300mg/kg/day DB107-FC PO concurrent with 2 Gy/day over 5 consecutive days during weeks 1-2, \& 5-6. After RT, participants receive 1.4 x 10\^9 TU/mL DB107-RRV IV on days 7 and 14. IV DB107-RRV occurs during a 4-week rest period between RT and adjuvant portions of the protocol. Participants who begin adjuvant therapy receive 300 mg/kg/day DB107-FC PO on days 1-5 of a 28-day cycle for up to 6 cycles or until PD with 150-200 mg/m\^2 adjuvant TMZ per SOC on days 1-5 of each cycle for up to 6 cycles. Participants with no PD may continue to receive additional cycles of DB107-FC PD, withdrawal, death or study closure. Participants will be followed up for safety and survival status for up to 15 years.
Interventions
Given intracranially (IC) during resection and intravenously (IV) immediately following
Given orally (PO)
Undergo standard of care MRI
Undergo RT
Given PO
Undergo non-investigational tumor resection
Eligibility Criteria
You may qualify if:
- Participant has provided written informed consent.
- Participant is between 18 years of age and 75 years of age, inclusive.
- Participant must have a Karnofsky Performance Scale (KPS) of \>= 70.
- Participant must have newly diagnosed adult-type diffuse gliomas (World Health Organization Classification 2021) that has not been previously treated with surgery, radiation or chemotherapy (specifically astrocytoma, Isocitrate dehydrogenase (IDH)-mutant or glioblastoma, IDH-wildtype).
- Based on the pre-operative evaluation by neurosurgeon, participant is a candidate for \>= 80% resection of the enhancing region.
- The primary tumor must be made available for central testing for IDH1 mutation, O6-methylguanine-DNA methyl-transferase (MGMT) methylation status.
- Willing to provide a blood sample to determine Denovo Genomic Marker 7 (DGM7) status.
- Laboratory values adequate for patient to undergo surgery, including:
- Platelet count \>= 60,000/mm\^3
- Hemoglobin \>= 10 g/dL
- Absolute neutrophil count (ANC) \>= 1,500/mm\^3
- Absolute lymphocyte count \>= 500/mm\^3
- Total bilirubin \<=1.5 x upper limit of normal (ULN) (unless patient had Gilbert's syndrome)
- alanine aminotransferase (ALT) \<= 2.5 x ULN
- Estimated glomerular filtration rate of at least 50 mL/min by Cockcroft Gault Formula
- +6 more criteria
You may not qualify if:
- Prior treatment for High Grade Glioma (HGG).
- Histological confirmed oligodendroglioma (IDH-mutant and 1p.19q-codeleted) or mixed glioma.
- A contrast-enhancing brain tumor that is any of the following:
- Multi-focal (defined as 2 separate areas of presumed tumor whether contrast enhancing or not, measuring at least 1cm in 2 planes that are not contiguous
- Associated with either diffuse subependymal or leptomeningeal dissemination or
- \> 5cm in any dimension.
- Participant has or had an active infection requiring antibiotic, antifungal or antiviral therapy in the 4 weeks preceding study Cycle 1: Day 1.
- Participant has any bleeding diathesis, or must take anticoagulants, or antiplatelet agents, including nonsteroidal anti-inflammatory drugs (NSAIDs), at the time of the scheduled resection that cannot be interrupted for surgery.
- Participant is HIV positive.
- Participant has Hepatitis B (positive test for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and positive test for hepatitis B Virus (HBV) DNA) or Hepatitis C (positive tests for hepatitis C Virus (HCV) Antibody and HCV-RNA) or Hepatitis B and C co-infection (positive test for HBsAg or HBcAb and positive test for HCV Antibody).
- Participant has a history of allergy or intolerance to flucytosine (DB107-FC).
- Participant has a gastrointestinal disease that would, in the opinion of the Investigator, prevent him or her from being able to swallow or absorb flucytosine.
- Participant intends to undergo treatment with the Gliadel® wafer at the time of resection surgery or has received Gliadel® wafer \< 30 days from Cycle 1: Day 1.
- Severe pulmonary, cardiac or other systemic disease, which as per Investigator assessment would prevent surgical resection.
- Participant who have any other disease or condition, which as per Investigator assessment may affect the participant's compliance or place the participant at higher risk of potential treatment complications.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of California, San Franciscolead
- California Institute for Regenerative Medicine (CIRM)collaborator
- Denovo Biopharma LLCcollaborator
- Anova Enterprises, Inccollaborator
Study Sites (5)
University of Southern California
Los Angeles, California, 90089, United States
University of California, San Diego
San Diego, California, 92093, United States
University of California
San Francisco, California, 94143, United States
University of Miami
Miami, Florida, 33136, United States
Northwell Health
Lake Success, New York, 11042, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nicholas Butowski, MD
University of California, San Francisco
- PRINCIPAL INVESTIGATOR
Noriyuki Kasahara, MD, PhD
University of California, San Francisco
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor in Residence
Study Record Dates
First Submitted
July 9, 2024
First Posted
July 16, 2024
Study Start
January 8, 2025
Primary Completion (Estimated)
January 31, 2028
Study Completion (Estimated)
January 31, 2042
Last Updated
March 11, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Through study closeout
De-identified data may be shared with study collaborators and research partners