DB107-RRV + DB107-FC for Brain Tumors

Overseen By Leonela Wright, MSN, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ashish Shah

Must not be taking: Anticoagulants, NSAIDs, Bevacizumab, others

Disqualifiers: Other malignancy, HIV, Renal impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 12 months

33 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but certain medications like temozolomide, bevacizumab, and cytosine arabinoside must be stopped for a specific period before joining. Additionally, you cannot be on anti-coagulants or anti-platelet drugs that can't be stopped for surgery.

What makes the DB107-RRV + DB107-FC treatment unique for brain tumors?

This treatment is unique because it uses a virus to deliver a special enzyme to brain tumor cells, which then converts a harmless drug into a powerful cancer-fighting agent directly inside the tumor, potentially enhancing the effectiveness of radiation therapy and improving survival rates. ^{1 2 3 4 5}

Research Team

Ashish B. Shah, M.D.

Principal Investigator

University of Miami

Eligibility Criteria

This trial is for individuals with high-grade gliomas, a type of brain tumor including anaplastic astrocytoma and astrocytoma. It's aimed at those whose tumors have come back or are getting worse, whether they can be surgically removed or not.

Inclusion Criteria

I took my last dose of temozolomide 4 weeks before surgery.

I am mostly able to care for myself.

I am between 18 and 75 years old.

Exclusion Criteria

I plan to use or have recently used Gliadel® wafer during surgery.

Allergy to 5-FC

I have a stomach or intestine condition that affects how I absorb medicine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Patients receive DB107-RRV during the tumor resection/biopsy procedure

1 day

1 visit (in-person)

Treatment

Approximately 6 weeks after surgery, patients start a 7-day oral regimen of DB107-FC, repeated every 6 weeks for up to 12 months

12 months

Every 6 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• DB107-FC
• DB107-RRV

Trial Overview The study is testing a combination treatment using DB107-RRV (a retroviral replicating vector) and DB107-FC (flucytosine in tablet form) to see if it can shrink the tumors and help control the disease longer.

Participant Groups

Group I: DB107-RRV and DB107-FC Group Experimental Treatment 2 Interventions

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.

DB107-FC is already approved in United States, European Union for the following indications:

Approved in United States as DB107-FC for:

• None approved yet; Investigational for high-grade glioma (HGG) including glioblastoma (GBM)

Approved in European Union as DB107-FC for:

• None approved yet; Investigational for high-grade glioma (HGG) including glioblastoma (GBM); Orphan Drug Designation granted

Who Is Running the Clinical Trial?

Ashish Shah

Lead Sponsor

Trials

1

Recruited

30+

Denovo Biopharma LLC

Industry Sponsor

Trials

19

Recruited

3,200+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Using tumor-selective retroviral replicating vectors (RRV) expressing yeast cytosine deaminase (CD) significantly improved survival rates in a rodent model of glioma when combined with the pro-drug 5-fluorocytosine (5-FC).

Convection-enhanced delivery (CED) of RRV-CD resulted in better distribution of the treatment within the tumor and led to even greater survival benefits compared to simple injection methods, highlighting the importance of delivery method in enhancing therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Convection-enhanced delivery improves distribution and efficacy of tumor-selective retroviral replicating vectors in a rodent brain tumor model. Yin, D., Zhai, Y., Gruber, HE., et al.[2021]

Toca 511, a tumor-selective retroviral vector, effectively delivers the cytosine deaminase gene to glioma cells, enabling the conversion of the prodrug 5-fluorocytosine (5-FC) into the active anti-cancer drug 5-fluorouracil (5-FU) within the tumor cells.

The study found that 5-FU not only has direct cytotoxic effects but also enhances the effectiveness of radiation therapy, making it a promising strategy for treating aggressive brain tumors like glioblastoma in ongoing clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosensitization of gliomas by intracellular generation of 5-fluorouracil potentiates prodrug activator gene therapy with a retroviral replicating vector. Takahashi, M., Valdes, G., Hiraoka, K., et al.[2021]

In a phase 1 trial involving 45 subjects with recurrent high-grade glioma, Toca 511 demonstrated a statistically significant improvement in overall survival, averaging 13.6 months compared to an external control group.

Toca 511 and its prodrug Toca FC were well-tolerated, with the retroviral vector persisting in tumors while remaining controlled systemically, suggesting a promising safety profile for further testing in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 trial of vocimagene amiretrorepvec and 5-fluorocytosine for recurrent high-grade glioma. Cloughesy, TF., Landolfi, J., Hogan, DJ., et al.[2022]

In a phase I trial involving 56 patients with recurrent high-grade glioma, the combination of vocimagene amiretrorepvec (Toca 511) and extended-release 5-fluorocytosine (Toca FC) resulted in durable complete responses in 21.7% of patients, with a median follow-up of 35.7 months for responders.

All patients who achieved a durable response remained alive and in response for over 33.9 months, indicating a potential link between durable responses and improved overall survival, particularly in those with IDH1 mutant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable complete responses in some recurrent high-grade glioma patients treated with Toca 511 + Toca FC. Cloughesy, TF., Landolfi, J., Vogelbaum, MA., et al.[2020]

The study demonstrated that retroviral replicating vectors (RRV) can effectively deliver therapeutic genes to lung cancer cells, showing rapid viral replication and high transduction efficiency in both in vitro and in vivo models.

Toca 511, an RRV encoding a yeast enzyme that activates the prodrug 5-fluorocytosine, significantly inhibited tumor growth and improved overall survival in lung cancer models, indicating its potential as a novel treatment strategy for pulmonary malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retroviral Replicating Vector Toca 511 (Vocimagene Amiretrorepvec) for Prodrug Activator Gene Therapy of Lung Cancer. Kushiya, H., Hiraoka, K., Suzuki, T., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Convection-enhanced delivery improves distribution and efficacy of tumor-selective retroviral replicating vectors in a rodent brain tumor model. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Radiosensitization of gliomas by intracellular generation of 5-fluorouracil potentiates prodrug activator gene therapy with a retroviral replicating vector. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Phase 1 trial of vocimagene amiretrorepvec and 5-fluorocytosine for recurrent high-grade glioma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Durable complete responses in some recurrent high-grade glioma patients treated with Toca 511 + Toca FC. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Retroviral Replicating Vector Toca 511 (Vocimagene Amiretrorepvec) for Prodrug Activator Gene Therapy of Lung Cancer. [2022]