Virus-Based Drug Therapy for Brain Tumor

(rQNestin Trial)

Recruiting at 4 trial locations

Overseen By E. Antonio Chiocca, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Antivirals, Immunosuppressants, Anti-VEGF

Disqualifiers: Systemic malignancy, Chronic infections, others

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

Compensation: Varies

Number of Visits: 8

Duration: Approximately 4 months

62 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is evaluating an investigational drug, an oncolytic virus called rQNestin34.5v.2. This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug as a possible treatment for this diagnosis of recurrent or progressive brain tumor.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop all current medications, but certain medications must be stopped before participating. For example, you must stop taking dexamethasone at least 14 days before the first treatment and antiviral medications like valacyclovir, acyclovir, or ganciclovir at least 7 days before surgery.

What data supports the effectiveness of the drug rQNestin34.5v.2 for brain tumors?

Research shows that oncolytic viruses, which are viruses engineered to target and destroy cancer cells, have been promising in treating brain tumors like gliomas. Similar viruses have been tested in clinical trials and have shown safety and some effectiveness in targeting and killing tumor cells while sparing healthy brain cells. ^{1 2 3 4 5}

How is the virus-based drug rQNestin34.5v.2 different from other brain tumor treatments?

rQNestin34.5v.2 is unique because it uses a virus to specifically target and destroy tumor cells in the brain, while leaving healthy cells unharmed. This approach, known as oncolytic virotherapy, is different from traditional treatments like surgery or chemotherapy, which can affect both cancerous and healthy cells. ^{1 3 4 6 7}

Research Team

E. Antonio Chiocca, MD, PhD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

Adults over 18 with recurrent brain tumors who've had prior radiation and chemotherapy, have a Karnofsky Performance Score ≥70, and can tolerate multiple biopsies. They must not be pregnant or breastfeeding, agree to use contraception, and have no severe infections or immune disorders. Tumors must meet specific size/location criteria.

Inclusion Criteria

For use of other investigational drug or other anti-tumor treatment, specific time periods must have elapsed from the projected start of scheduled study treatment

My first surgery biopsy confirmed I have glioma.

I have been diagnosed with a specific type of brain tumor that is not IDH mutant.

Exclusion Criteria

I have a chronic infection with HIV, hepatitis B, or C.

I am currently being treated for an active infection.

I have had cancer that needed treatment beyond surgery in the last 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intratumoral administration of rQNestin34.5v.2, with or without Cyclophosphamide pre-treatment, following a dose escalation design

Approximately 4 months

6 visits (in-person) on days 0, 15, 30, 60, 90, and 120

Follow-up

Participants are monitored for safety and effectiveness after treatment, including MRI evaluations and assessments of HSV1 viremia and antibody response

1 year

Evaluations every 2 months

Treatment Details

Interventions

• rQNestin34.5v.2

Trial Overview The trial is testing rQNestin34.5v.2, an investigational oncolytic virus for safety and proper dosage against recurrent malignant glioma. It includes cyclophosphamide treatment and stereotactic biopsy in a Phase I clinical setting.

Participant Groups

Group I: Arm C- Multiple Dose rQNestin Experimental Treatment 2 Interventions

Arm C includes up to 6 intratumoral repeated doses of rQNestin34.5v.2, first in a cohort receiving 10\^8 pfus per time point, followed by a cohort receiving 10\^9 or 10\^7 pfus per time point. * Arm C adds 2 cohorts of 12 subjects in an open-label clinical trial of rQNestin34.5v.2 administered at two dose levels * The injections are planned for days 0, 15, 30, 60, 90, and 120 * Subjects with presumed radiologic evidence of recurrent malignant glioma will undergo stereotactic biopsy under monitored general or local anesthesia. Evidence of recurrent high grade or malignant must be found on frozen section for the person to receive administration of the agent.

Group II: Arm B- rQNestin+CPA Experimental Treatment 3 Interventions

Arm B is rQNestin34.5v.2 treatment with Cyclophosphamide (CPA) pre-treatment This study follows a standard 3+3 dose escalation design. Participants will not enroll to Arm B until the MTD or HTD has been met for Arm A. * Cyclophosphamide one intravenous injection 2 days prior to procedure. * Subjects with presumed radiologic evidence of recurrent malignant glioma will undergo stereotactic biopsy under monitored general or local anesthesia. Evidence of recurrent high grade or malignant must be found on frozen section for the person to receive administration of the agent. * rQNestin34.5v.2 Indicated dose as per cohort, Intratumor administration during surgery, single dose

Group III: Arm A- rQNestin Experimental Treatment 2 Interventions

Arm A is rQNestin34.5v.2 treatment This study follows a standard 3+3 dose escalation design. Participants will not enroll to Arm B until the MTD or HTD has been met for Arm A. * Subjects with presumed radiologic evidence of recurrent malignant glioma will undergo stereotactic biopsy under monitored general or local anesthesia. Evidence of recurrent high grade or malignant must be found on frozen section for the person to receive administration of the agent. * rQNestin34.5v.2 Indicated dose as per cohort, Intratumor administration during surgery, single dose

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Candel Therapeutics, Inc.

Industry Sponsor

Trials

12

Recruited

1,300+

Findings from Research

Glioblastoma multiforme (GBM) is a highly challenging cancer due to its aggressive nature and the difficulty in treating it effectively with current methods, which have only shown modest improvements in patient outcomes.

Oncolytic virotherapy, which uses genetically engineered viruses to target and destroy cancer cells, shows promise as a new treatment approach for GBM, with various viral vectors like herpes simplex and poliovirus currently in different stages of clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunovirotherapy for the Treatment of Glioblastoma and Other Malignant Gliomas. Estevez-Ordonez, D., Chagoya, G., Salehani, A., et al.[2023]

The study found that the oncolytic viruses VSV-ΔM51 and vvDD can effectively infect and kill temozolomide (TMZ) resistant brain tumor stem cells (BTSCs) and their differentiated cells, indicating a potential new treatment option for patients who do not respond to standard chemotherapy.

Both viruses were shown to inhibit the self-renewal activity of TMZ resistant BTSCs in vitro, suggesting they could serve as a promising supplement to existing GBM therapies, especially for those with resistance to TMZ.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide resistant human brain tumor stem cells are susceptible to recombinant vesicular stomatitis virus and double-deleted Vaccinia virus in vitro. Jiang, B., Lun, X., Hao, X., et al.[2018]

Gene therapy using replication-competent viruses, like engineered herpes simplex-1 virus mutants G207 and HSV1716, shows promise in selectively targeting and destroying primary brain tumors while sparing healthy neurons, as demonstrated in Phase I trials for recurrent high-grade glioma.

The review also highlights ongoing research into other viral therapies, such as Newcastle disease virus and adenovirus mutant ONYX-015, which may offer additional strategies for treating malignant gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic viruses: clinical applications as vectors for the treatment of malignant gliomas. Shah, AC., Benos, D., Gillespie, GY., et al.[2023]

Oncolytic viruses have shown promise as a safe treatment option for malignant brain tumors, particularly glial tumors, with some patients experiencing impressive results from viral therapy.

The effectiveness of oncolytic virotherapy varies among patients due to the high genetic heterogeneity of tumor cells, highlighting the need for further advancements in treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oncolytic viruses for therapy of malignant glioma]. Sosnovtceva, AO., Grinenko, NF., Lipatova, AV., et al.[2018]

Oncolytic viruses (OVs) show promise as a novel treatment for malignant gliomas, which are difficult to treat with conventional therapies, as they can selectively target and kill cancer cells.

Clinical trials have demonstrated the safety of various OVs, such as herpes simplex virus and adenovirus, while also indicating their potential effectiveness against malignant gliomas, suggesting a new avenue for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EXPLORING THE ANTITUMOR EFFECT OF VIRUS IN MALIGNANT GLIOMA. Saha, D., Ahmed, SS., Rabkin, SD.[2020]

The study developed three mathematical models to analyze the effects of Vesicular Stomatitis Virus (VSV) on glioblastoma (GBM) cells, showing that a more complex model incorporating time-delay effects accurately predicts the virus's dynamics in vitro.

The findings suggest that the delay time is a critical factor in modeling the lytic action of VSV on GBM, providing a foundation for future simulations of in vivo treatments for various cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A mathematical approach to virus therapy of glioblastomas. de Rioja, VL., Isern, N., Fort, J.[2019]

Viruses are being explored as innovative therapies for malignant gliomas, serving both as vectors for delivering therapeutic genes and as agents that can selectively destroy tumor cells.

Current clinical trials have utilized retroviral and adenoviral vectors to enhance tumor susceptibility to treatments, as well as conditionally replicating HSV viruses, showing promise but indicating a need for further research into additional viral options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Viruses in the treatment of brain tumors. Fecci, PE., Gromeier, M., Sampson, JH.[2019]

References

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

Immunovirotherapy for the Treatment of Glioblastoma and Other Malignant Gliomas. [2023]

2. France pubmed.ncbi.nlm.nih.gov

Temozolomide resistant human brain tumor stem cells are susceptible to recombinant vesicular stomatitis virus and double-deleted Vaccinia virus in vitro. [2018]

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

Oncolytic viruses: clinical applications as vectors for the treatment of malignant gliomas. [2023]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Oncolytic viruses for therapy of malignant glioma]. [2018]

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

EXPLORING THE ANTITUMOR EFFECT OF VIRUS IN MALIGNANT GLIOMA. [2020]

6. England pubmed.ncbi.nlm.nih.gov

A mathematical approach to virus therapy of glioblastomas. [2019]

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

Viruses in the treatment of brain tumors. [2019]