RECRUITING

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

Conditions

High Grade Glioma MGMT-Unmethylated Glioblastoma MGMT-Methylated Glioblastoma Gene therapy Combination therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2025-01-08

Study Completion:2040-01-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06504381

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Participant has provided written informed consent. 2. Participant is between 18 years of age and 75 years of age, inclusive. 3. Participant must have a Karnofsky Performance Scale (KPS) of \>= 70. 4. 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). 5. Based on the pre-operative evaluation by neurosurgeon, participant is a candidate for \>= 80% resection of the enhancing region. 6. The primary tumor must be made available for central testing for IDH1 mutation, O6-methylguanine-DNA methyl-transferase (MGMT) methylation status. 7. Willing to provide a blood sample to determine Denovo Genomic Marker 7 (DGM7) status. 8. Laboratory values adequate for patient to undergo surgery, including: 1. Platelet count \>= 60,000/mm\^3 2. Hemoglobin \>= 10 g/dL 3. Absolute neutrophil count (ANC) \>= 1,500/mm\^3 4. Absolute lymphocyte count \>= 500/mm\^3 5. Total bilirubin \<=1.5 x upper limit of normal (ULN) (unless patient had Gilbert's syndrome) 6. alanine aminotransferase (ALT) \<= 2.5 x ULN 7. Estimated glomerular filtration rate of at least 50 mL/min by Cockcroft Gault Formula 9. 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. * Has not undergone a hysterectomy or bilateral oophorectomy or * Has not had \>= 12 months of non-therapy-induced amenorrhea. 10. Participants must not be breastfeeding. 11. 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.	1. Prior treatment for High Grade Glioma (HGG). 2. 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. 3. Histological confirmed oligodendroglioma (IDH-mutant and 1p.19q-codeleted) or mixed glioma. 4. A contrast-enhancing brain tumor that is any of the following: 1. 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 2. Associated with either diffuse subependymal or leptomeningeal dissemination or 3. \> 5cm in any dimension. 5. Participant has or had an active infection requiring antibiotic, antifungal or antiviral therapy in the 4 weeks preceding study Cycle 1: Day 1. 6. 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. 7. Participant is HIV positive. 8. 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). 9. Participant has a history of allergy or intolerance to flucytosine (DB107-FC). 10. 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. 11. 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. 12. Severe pulmonary, cardiac or other systemic disease, which as per Investigator assessment would prevent surgical resection. 13. 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.

Inclusion Criteria

Exclusion Criteria

1. Participant has provided written informed consent.
2. Participant is between 18 years of age and 75 years of age, inclusive.
3. Participant must have a Karnofsky Performance Scale (KPS) of \>= 70.
4. 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).
5. Based on the pre-operative evaluation by neurosurgeon, participant is a candidate for \>= 80% resection of the enhancing region.
6. The primary tumor must be made available for central testing for IDH1 mutation, O6-methylguanine-DNA methyl-transferase (MGMT) methylation status.
7. Willing to provide a blood sample to determine Denovo Genomic Marker 7 (DGM7) status.
8. Laboratory values adequate for patient to undergo surgery, including:
1. Platelet count \>= 60,000/mm\^3
2. Hemoglobin \>= 10 g/dL
3. Absolute neutrophil count (ANC) \>= 1,500/mm\^3
4. Absolute lymphocyte count \>= 500/mm\^3
5. Total bilirubin \<=1.5 x upper limit of normal (ULN) (unless patient had Gilbert's syndrome)
6. alanine aminotransferase (ALT) \<= 2.5 x ULN
7. Estimated glomerular filtration rate of at least 50 mL/min by Cockcroft Gault Formula
9. 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.
* Has not undergone a hysterectomy or bilateral oophorectomy or
* Has not had \>= 12 months of non-therapy-induced amenorrhea.
10. Participants must not be breastfeeding.
11. 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.

1. Prior treatment for High Grade Glioma (HGG).
2. 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.
3. Histological confirmed oligodendroglioma (IDH-mutant and 1p.19q-codeleted) or mixed glioma.
4. A contrast-enhancing brain tumor that is any of the following:
1. 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
2. Associated with either diffuse subependymal or leptomeningeal dissemination or
3. \> 5cm in any dimension.
5. Participant has or had an active infection requiring antibiotic, antifungal or antiviral therapy in the 4 weeks preceding study Cycle 1: Day 1.
6. 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.
7. Participant is HIV positive.
8. 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).
9. Participant has a history of allergy or intolerance to flucytosine (DB107-FC).
10. 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.
11. 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.
12. Severe pulmonary, cardiac or other systemic disease, which as per Investigator assessment would prevent surgical resection.
13. 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.

Contacts and Locations

Study Contact

Stephanie Lewis, RN

CONTACT

(415) 353-2193

stephanie.lewis2@ucsf.edu

Neuro-Oncology New Patient Coordinator, RN

CONTACT

NeuroOncNewPatientCoord@ucsf.edu

Principal Investigator

Nicholas Butowski, MD

PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Noriyuki Kasahara, MD, PhD

PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Study Locations (Sites)

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

Collaborators and Investigators

Sponsor: Nicholas Butowski

Nicholas Butowski, MD, PRINCIPAL_INVESTIGATOR, University of California, San Francisco
Noriyuki Kasahara, MD, PhD, PRINCIPAL_INVESTIGATOR, University of California, San Francisco

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-01-08

Study Completion Date2040-01-31

Study Record Updates

Study Start Date2025-01-08

Study Completion Date2040-01-31

Terms related to this study

Keywords Provided by Researchers

Gene therapy
Combination therapy

Additional Relevant MeSH Terms

High Grade Glioma
MGMT-Unmethylated Glioblastoma
MGMT-Methylated Glioblastoma