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High Grade GliomaPhase 1/2NCT06504381

DB107-RRV, DB107-FC, and Radiation Therapy With or Without Temozolomide (TMZ) for High Grade Glioma

A Phase 1/2 study testing DB107-RRV, DB107-FC and Radiation Therapy (RT) in people with High Grade Glioma and MGMT-Unmethylated Glioblastoma, run by University of California, San Francisco at 5 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
DB107-RRV, DB107-FC and Radiation Therapy (RT)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
5 sitesUnited States
Study dates
8 Jan 2025to 31 Jan 2042
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Each patient must meet all of the following inclusion criteria to be eligible for study entry:
  • 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.
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  • 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
  • Female participants of child-bearing potential and male participants must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for 30-days prior to the first administration of study drug, for the duration of study participation, and for 90-days following completion of the therapy. Should a female participant become pregnant or suspect a pregnancy while participating in this study, the treating physician must be informed immediately. IF a male participant impregnates or is suspected of impregnating a woman while participating in this study, the treating physician must be informed immediately.
  • A female of child-bearing potential is any women (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • Has not undergone a hysterectomy or bilateral oophorectomy or
  • Has not had >= 12 months of non-therapy-induced amenorrhea.
  • Participants must not be breastfeeding.
  • Participants must have the ability to understand, and the willingness to comply with the scheduled visits, treatment schedule, laboratory testing and other requirements of the study.

Who cannot join

  • Participants may not meet any of the following exclusion criteria to be eligible for study entry:
  • Prior treatment for High Grade Glioma (HGG).
  • History of other malignancy unless the participant has been disease-free for at least 5 years. Adequately treated basal cell carcinoma or squamous cell skin cancer is not exclusionary regardless of time, as well as localized prostate carcinoma or cervical carcinoma in situ after curative treatment.
  • 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
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  • 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.

Trial locations and contacts

5 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Stephanie Lewis, RN contact

(415) 353-2193

stephanie.lewis2@ucsf.edu

Neuro-Oncology New Patient Coordinator contact

NeuroOncNewPatientCoord@ucsf.edu

5 sites in 1 country

United States5 sites, 5 recruiting

  • Northwell Health

    Lake Success, New York, 11042

    516-941-1260, CI-NeuroDMT@northwell.edu

    Samuel Singer, MD

    Recruiting

  • University of Southern California

    Los Angeles, California, 90089

    (323) 409-7422, tcchen@usc.edu

    Thomas Chen, MD

    Recruiting

  • University of Miami

    Miami, Florida, 33136

    (305) 243-0864, xw612@med.miami.edu

    Ashish Shah, MD

    Recruiting

  • University of California, San Diego

    San Diego, California, 92093

    858-822-5354, CancerCTO@health.ucsd.edu

    David Piccioni, MD, PhD

    Recruiting

  • University of California

    San Francisco, California, 94143

    Stephanie Lewis, RN, (415) 353-2193, stephanie.lewis2@ucsf.edu

    Neuro-Oncology New Patient Coordinator, NeuroOncNewPatientCoord@ucsf.edu

    Recruiting

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
DB107-RRV, DB107-FC, Radiation Therapy (RT), Temozolomide, Magnetic Resonance Imaging (MRI)
Keywords
Gene therapy, Combination therapy
Medical subject headings
Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DB107-RRVGenetic

    Also called Toca 511, Vocimagene amiretrorepvec

    Given intracranially (IC) during resection and intravenously (IV) immediately following

  • DB107-FCDrug

    Also called Toca FC, Extended-release 5-fluorocytosine, 5-fluorocytosine

    Given orally (PO)

  • Radiation Therapy (RT)Radiation

    Also called Radiation Treatment

    Undergo RT

  • TemozolomideDrug

    Also called Temozolomide (TMZ)

    Given PO

  • Magnetic Resonance Imaging (MRI)Procedure or surgery

    Also called MR, MRI

    Undergo standard of care MRI

  • Surgical resectionProcedure or surgery

    Also called Surgical tumor resection, Brain surgery

    Undergo non-investigational tumor resection

Study groups in NCT06504381
Study groupRoleWhat they receive
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.
Receives: Genetic: DB107-RRV; Drug: DB107-FC; Radiation: Radiation Therapy (RT); Drug: Temozolomide; Procedure: Magnetic Resonance Imaging (MRI); Procedure: Surgical resection
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.
Receives: Genetic: DB107-RRV; Drug: DB107-FC; Radiation: Radiation Therapy (RT); Drug: Temozolomide; Procedure: Magnetic Resonance Imaging (MRI); Procedure: Surgical resection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 1 year

  2. 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.

    Measured: Up to 3 years

  3. 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.

    Measured: Up to 3 years

Secondary outcomes (6)

  1. Recommended Phase 2 Dose (RP2D) (Phase I)

    The confirmed RP2D of DB107-RRV and DB107-FC implemented for participants enrolled in Phase IIa will be reported.

    Measured: Up to 1 year

  2. Overall Response Rate (ORR) (Phase IIa)

    ORR is defined as the percentage of subjects who obtained either a disease status of CR or PR according to iRANO criteria per investigator.

    Measured: Up to 5 years

  3. Median Progression-free survival (PFS) at 6 months (Phase IIa)

    PFS is defined as time from first receipt of DB107-RRV until progression or death, whichever occurs first at the 6-month visit. 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.

    Measured: Up to 6 months

  4. Median Progression-free survival (PFS) (Phase IIa)

    PFS is defined as time from first receipt of DB107-RRV until progression or death, whichever occurs first at the 6-month visit. 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.

    Measured: 6 months

  5. Median Overall Survival (OS) at 6 months (Phase IIa)

    Overall survival at 6 months is defined as the time from the date of first DB107-RRV injection until death. Participants who are alive at 6 months will be censored. The median and the 95% confidence interval will be estimated using the Kaplan-Meier method.

    Measured: 6 months

  6. Median Overall Survival (OS) (Phase IIa)

    Overall survival will be analyzed using the date of first DB107-RRV injection as baseline until death, participant withdrawal, or study closure. The median and the 95% confidence interval will be estimated using the Kaplan-Meier method.

    Measured: Up to 15 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jul 2024
  2. Study start8 Jan 2025
  3. Primary completion31 Jan 2028 (estimated)
  4. Study completion31 Jan 2042 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06504381
Sponsor's protocol ID
231017
Other IDs
511-18-01, CLIN2-15311, NCI-2025-00178
Status last verified
Mar 2026
First submitted
9 Jul 2024
Last updated
11 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified data may be shared with study collaborators and research partners

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing DB107-RRV, DB107-FC and Radiation Therapy (RT) in people with High Grade Glioma and MGMT-Unmethylated Glioblastoma, run by University of California, San Francisco at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 11 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Stephanie Lewis, RN ((415) 353-2193, stephanie.lewis2@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of participants with dose limiting toxicities (Phase I) (time frame: Up to 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06504381.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2026.

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