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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment to determine if it can shrink high-grade glioma (HGG), a type of brain tumor, and maintain control over it. Participants will receive two investigational drugs: DB107-RRV (also known as Toca 511 or vocimagene amiretrorepvec) administered during surgery, and DB107-FC (also known as Flucytosine Extended-Release Tablets or 5-fluorocytosine) taken as a pill every six weeks for up to a year. The trial seeks individuals with recurrent brain tumors who have the Denovo Genomic Marker 7 in their blood. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of treatments DB107-RRV and DB107-FC has been promising, especially for brain tumors like high-grade gliomas. In one study with 45 participants, DB107-RRV helped individuals with recurring high-grade glioma live longer, suggesting that most patients tolerated the treatment well.

Another study found that DB107-RRV specifically targeted the tumor without harming normal brain tissue, indicating a positive safety profile by reducing the risk of damaging healthy cells.

DB107-FC has been tested on solid tumors, including high-grade gliomas and colorectal cancer, with a focus on safety. These trials aim to ensure that any side effects are manageable.

Overall, while more research is needed, current data is encouraging regarding the safety of these treatments. Participants should be aware that although early trials suggest the treatment is generally well-tolerated, all medical treatments can have side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about DB107-RRV and DB107-FC for brain tumors because these treatments offer a unique approach compared to existing options like surgery, radiation, and chemotherapy. DB107-RRV is administered during tumor resection, potentially targeting cancer cells directly during surgery, which is different from traditional post-surgical therapies. DB107-FC is an oral medication that patients can self-administer, which provides convenience and continuous treatment, potentially improving patient adherence and outcomes. This combination could offer a more targeted and patient-friendly approach, possibly enhancing effectiveness and quality of life for those with brain tumors.

What evidence suggests that this trial's treatments could be effective for high-grade glioma?

Research has shown that the combination of DB107-RRV and DB107-FC, which participants in this trial will receive, may help treat high-grade gliomas (HGG), a type of brain tumor. One study found that 61% of patients had their disease controlled, with an average survival time of 9.6 months. Although earlier treatments for similar brain tumors did not always extend survival, some patients lived longer. This new therapy aims to attack cancer cells while sparing healthy brain tissue. Early results suggest it might significantly improve survival time, potentially giving patients more time. While more data is needed, these findings offer hope for better management of HGG. ^{1 3 4 6 7}

Who Is on the Research Team?

Ashish B. Shah, M.D.

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

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.

My high-grade glioma has come back or gotten worse.

Exclusion Criteria

Allergy to 5-FC

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06504381

Study Details | NCT06504381 | DB107-RRV, ... 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 ...

2. synapse.patsnap.com synapse.patsnap.com/article/anova-begins-phase-12a-study-of-db107-for-high-grade-gliomas-with-first-patient-enrolled

Anova Begins Phase 1/2a Study of DB107 for High-Grade ... This trial is focused on evaluating DB107 as a potential treatment for brain tumors, particularly high-grade gliomas (HGG). The study, a Phase 1 ...

3. biospace.com biospace.com/press-releases/anova-announces-first-patient-enrolled-to-phase-1-2a-study-of-db107-for-the-treatment-of-high-grade-gliomas

Anova Announces First Patient Enrolled to Phase 1/2a ... DB107 is an investigational gene therapy being developed by Denovo Biopharma for the treatment of HGG, including glioblastoma multiforme (GBM).

4. withpower.com withpower.com/trial/phase-2-glioma-8-2024-2f776

DB107-RRV + DB107-FC for Brain Tumors 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 ...

5. reporter.nih.gov reporter.nih.gov/project-details/9550798

Phase 2/3 Study of Toca 511-Toca FC vs SOC in Recurrent ... Preliminary efficacy analyses indicate a substantially prolonged median survival, with an approximate 6-month improvement relative to clinical trials of drugs ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11878440/

An Update on the Clinical Status, Challenges, and Future ... Malignant gliomas are common central nervous system tumors that pose a significant clinical challenge due to the lack of effective treatments.

7. withpower.com withpower.com/trial/phase-2-anaplastic-astrocytoma-aa-4-2024-0af2a

DB107-RRV + DB107-FC for Brain Tumors In a phase 1 trial involving 45 subjects with recurrent high-grade glioma, Toca 511 demonstrated a statistically significant improvement in overall survival, ...