DB107-Retroviral Replicating Vector (RRV) Combined With DB107-Flucytosine (FC) in Patients With Recurrent Glioblastoma or Anaplastic Astrocytoma

NCT06264388 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 20231234R21CA282543
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if the investigational products, DB107-RRV and DB107-FC, as a combination treatment will shrink high-grade glioma (HGG) in patients with recurrent/progressive, resectable or unresectable disease and increase the time that disease is controlled.

Conditions

High Grade Glioma; Anaplastic Astrocytoma

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival

  Progression free survival (PFS) is defined as duration from initiation of treatment to the point of disease progression or death.

  Up to 24 Months

• Overall Survival

  Overall survival (OS) refers to the duration from the initiation of enrollment until death, regardless of the cause.

  Up to 24 Months

Secondary Outcomes (5)

• Assessment of Tumor Status Measured by Response Assessment in Neuro-oncology (RANO) Criteria

  Up to 5 Years

• Number of Treatment Related Toxicities

  Up to 5 Years

• Durable Response Rate (DRR)

  Up to 5 Years

• Durable Clinical Benefit Rate (DCBR)

  Up to 5 Years

• Duration of Durable Response Rate

  12 Months

Study Arms (1)

DB107-RRV and DB107-FC Group

EXPERIMENTAL

Patients will receive DB107-RRV during the tumor resection/biopsy procedure. Approximately 6 weeks after surgery, patients will start drug therapy with a 7-day oral regimen of 220 mg/kg/day DB107-FC, which is to be self-administered. This 7-day regimen, which is considered one cycle of treatment, is to be repeated every 6 weeks for up to 12 months. Patients will undergo follow up procedures for at least 5 years after last DB107-RRV treatment.

Drug: DB107-RRV; Drug: DB107-FC

Interventions

DB107-RRV DRUG

Patients will undergo surgery to remove as much of the high-grade glioma (HHG) tumor as possible and will receive combination intravenous (IV) and adaptive repeat intratumoral delivery of DB107-RRV in the vein (IV) and in the walls of the cavity that remains where tumor is removed.

DB107-RRV and DB107-FC Group

DB107-FC DRUG

Patients will start taking DB107-FC three times by mouth every day for a period of seven days, which is one cycle of treatment. A cycle of treatment is medication taken on a set schedule with periods of rest in between. Patients will wait five weeks before taking the next seven day course of DB107-FC. The first dose of DB107-FC will be taken at the hospital or clinic; afterward, patients will take the doses of DB107-FC at home. Patients will take DB107-FC for up to 12 months after surgery.

Also known as: Ancobon, Ancotil

DB107-RRV and DB107-FC Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 18-75 years old.
• Histologically proven HGG that have recurred/progressed (first or second recurrence).
• Patients with unresectable or resectable HGG (AA or GBM) will be enrolled.
• Measurable disease on MRI as evidenced by 1 cm on two separate dimensions on MRI fluid attenuated inversion recovery (FLAIR) (non-enhancing) or contrast-enhancement.
• Last temozolomide dosage 4 weeks prior to surgery.
• Patients with prior radiation therapy are allowed, but histological tumor diagnosis of recurrent tumor must be confirmed according to the RANO criteria. Recurrence must be confirmed by diagnostic biopsy with local pathology review or contrast-enhanced MRI. If first recurrence of GBM is documented by MRI, an interval of at least 12 weeks after the end of prior radiation therapy is required unless there is either: i) histopathologic confirmation of recurrent tumor, or ii) new enhancement on MRI outside of the radiotherapy treatment field.
• Presence of Denovo Genomic Marker 7 (DGM7) biomarker in blood.
• Laboratory values (Platelet count ≥ 80,000, hemoglobin \[Hg\] ≥10 g/dL, absolute neutrophil count (ANC) \> 1,500 cells/mm3, absolute lymphocyte count (ALC) \> 500/mm3) and adequate liver function, total bilirubin\< 1.5 upper limit of normal (ULN), alanine transaminase (ALT) \<2.5 ULN. Estimated glomerular filtration rate (eGFR) should be \> 50 mL/min (Cockcroft Gault Formula). Patients with aspartate transaminase (AST) or ALT values \>3 ULN and total bilirubin \>1.5 mg/dL will be excluded.
• Patients cannot be pregnant at the time of enrollment or during the study. Patients willing to use one (1) effective method of contraception in addition to barrier methods (condoms) from the time of signing the informed consent form until 12 months after receiving the last dose of DB107-RRV or until there is no evidence of DB107-RRV in their blood, whichever is longer.
• Karnofsky Performance Score (KPS) ≥ 70.
• Patient is able to consent and abide by protocol.

You may not qualify if:

• History of active other malignancy (other than non-melanoma skin cancers, cervical ductal carcinoma in situ or localized prostate cancer) within 5 years.
• Multifocal gliomas that cannot undergo stereotactic biopsy/administration of DB107-RRV will be excluded. Patients with 3 or more intracranial recurrences will be excluded.
• Histologically confirmed oligodendroglioma or mixed gliomas.
• History of human immunodeficiency virus (HIV) infection or other forms of severe immunosuppression.
• Patients with impaired renal function (eGFR\<50 cc/min).
• Patients with bone marrow depression, such as those with a hematological disease or who are being treated with radiation or drugs that depress bone marrow or individuals who have a history of treatment with drugs or radiation that depress bone marrow within 1 month of enrollment.
• The patient intends to undergo treatment with the Gliadel® wafer at the time of this surgery or has received the Gliadel® wafer \< 30 days from surgery.
• Allergy to 5-FC.
• Gastrointestinal diseases that prevent absorption of medications such as 5-FC.
• Pregnancy or patients who are actively breast-feeding.
• Recent use of cytosine arabinoside (\< 3 weeks).
• Recent treatment with bevacizumamab (\< 3 weeks).
• Recent treatment with temozolomide (\<4 weeks).
• History of bleeding diathesis or current anti-coagulant or anti-platelet usage, including nonsteroidal anti-inflammatory drugs (NSAIDs), at the time of the scheduled resection that cannot be stopped for surgery.
• Sustained dependence on systemic dexamethasone (\>8 mg/day) one month prior to surgery.

Sponsors & Collaborators

• Ashish Shah: lead
• Denovo Biopharma LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Miami Hospital

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Glioma; Astrocytoma

Interventions

Flucytosine

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Cytosine; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ashish Shah, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leonela Wright, MSN, RN

CONTACT

305-243-0864; lxw612@med.miami.edu

Ashish Shah, MD

CONTACT

3052436946; ashah@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical

Study Record Dates

• First Submitted: February 8, 2024
• First Posted: February 20, 2024
• Study Start: May 1, 2024
• Primary Completion (Estimated): May 1, 2034
• Study Completion (Estimated): May 1, 2034
• Last Updated: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)