62 Participants Needed

Virus-Based Drug Therapy for Brain Tumor

(rQNestin Trial)

Recruiting at 4 trial locations
EA
EA
Overseen ByE. Antonio Chiocca, MD, PhD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

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.12345

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.13467

Research Team

EA

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.
See 12 more

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.
See 13 more

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 OverviewThe 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
3Treatment groups
Experimental Treatment
Group I: Arm C- Multiple Dose rQNestinExperimental Treatment2 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+CPAExperimental Treatment3 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- rQNestinExperimental Treatment2 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

Find a Clinic Near You

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

References

Immunovirotherapy for the Treatment of Glioblastoma and Other Malignant Gliomas. [2023]
Temozolomide resistant human brain tumor stem cells are susceptible to recombinant vesicular stomatitis virus and double-deleted Vaccinia virus in vitro. [2018]
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]
EXPLORING THE ANTITUMOR EFFECT OF VIRUS IN MALIGNANT GLIOMA. [2020]
A mathematical approach to virus therapy of glioblastomas. [2019]
Viruses in the treatment of brain tumors. [2019]