Trials / Recruiting
RecruitingNCT06504381
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
- Status
- Recruiting
- Phase
- Phase 1 / Phase 2
- Study type
- Interventional
- Enrollment
- 70 (estimated)
- Sponsor
- University of California, San Francisco · Academic / Other
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
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.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of DB107-RRV administered intracranially followed by intravenous (IV) DB107-RRV and DB107-FC (Phase I). II. To determine the median progression-free survival (PFS) (informed by biomarker status, DGM7 and patient subsets to minimally include genomic profile and histology) of newly diagnosed HGG patients treated with DB107-RRV combined with DB107-FC delivered with standard of care following tumor resection (Phase IIa). SECONDARY OBJECTIVES: I. To confirm the recommended Phase 2 Dose (RP2D) of DB107-RRV and DB107-FC when administered to newly diagnosed HGG patients (Phase I). II. To evaluate radiographic response by Immunotherapy response assessment in neuro-oncology (iRANO) (Phase I). III. To assess best overall response rates (complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD)) and overall response rate (CR and PR) of each arm and subset (Phase IIa). IV. To assess the duration of response of each arm and subset (Phase IIa). V. To assess the median overall PFS and PFS at month 6 (PFS-6) for each arm and subset (Phase IIa). VI. To assess the median overall survival of each arm and subset (Phase IIa). VII. To evaluate the safety of DB107-RRV administered intracranially followed by IV DB107-RRV and DB107-FC (Phase IIa). OUTLINE: Participants will initially be enrolled in Phase I and treated with DB107-RRV intracranially, at time of surgical resection, and intravenously within 8 hours following surgery. Pathology will be performed locally as per standard practice to confirm participant's HGG diagnosis and Isocitrate dehydrogenase 1 (IDH1) mutation status. Participants in Phase I will then be assigned to one of 2 cohorts: No MGMT methylation (MGMT unmethylated) which will receive DB107-FC and RT following DB107-RRV or Low-High MGMT methylated which will receive DB107-FC, Temozolomide (TMZ) and RT following DB107-RRV. The safety and tolerability will be examined for the Phase I participants and RP2D dose confirmed. New participants will then be enrolled in Phase IIa under the established RP2D determined in Phase I, with the first 2 participants receiving a safety run-in at the RP2D. Once participant safety and tolerability are confirmed, additional participants will be enrolled in the Phase IIa portion of the study. All participants who receive DB107-RRV and DB107-FC will be followed for up to15 years.
Conditions
Interventions
| Type | Name | Description |
|---|---|---|
| GENETIC | DB107-RRV | Given intracranially (IC) during resection and intravenously (IV) immediately following |
| DRUG | DB107-FC | Given orally (PO) |
| RADIATION | Radiation Therapy (RT) | Undergo RT |
| DRUG | Temozolomide | Given PO |
| PROCEDURE | Magnetic Resonance Imaging (MRI) | Undergo standard of care MRI |
| PROCEDURE | Surgical resection | Undergo non-investigational tumor resection |
Timeline
- Start date
- 2025-01-08
- Primary completion
- 2028-01-31
- Completion
- 2042-01-31
- First posted
- 2024-07-16
- Last updated
- 2026-03-11
Locations
5 sites across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT06504381. Inclusion in this directory is not an endorsement.