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

ConditionsHigh Grade GliomaMGMT-Unmethylated GlioblastomaMGMT-Methylated Glioblastoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of California, San Francisco

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

Disqualifiers

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.

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • DB107-RRV

    Genetic

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

  • DB107-FC

    Drug

    Given orally (PO)

  • Radiation Therapy (RT)

    Radiation

    Undergo RT

  • Temozolomide

    Drug

    Given PO

  • Magnetic Resonance Imaging (MRI)

    Procedure/Surgery

    Undergo standard of care MRI

  • Surgical resection

    Procedure/Surgery

    Undergo non-investigational tumor resection

Treatment groups

70 Participants
are divided into 2 treatment groups
Group A: No MGMT Methylation (DB107-RRV, DB107-FC, Radiation therapy)Experimental treatment 6 interventions
Group B: Low to High MGMT Methylation (DB107-RRV, DB107-FC, Temozolomide (TMZ), Radiation therapy)Experimental treatment 6 interventions

Trial outcomes

Primary outcomes

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.

Time frame
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.

Time frame
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.

Time frame
Up to 3 years

Secondary outcomes

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.

Time frame
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.

Time frame
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.

Time frame
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.

Time frame
6 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of California, San Francisco

Lead sponsor

California Institute for Regenerative Medicine (CIRM)

Collaborator

Denovo Biopharma LLC

Collaborator

Anova Enterprises, Inc

Collaborator

Source ClinicalTrials.gov
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