Virus-Based Drug Therapy for Brain Tumor
(rQNestin Trial)
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Dana-Farber Cancer Institute
Must not be taking: Antivirals, Immunosuppressants, Anti-VEGF
Disqualifiers: Systemic malignancy, Chronic infections, others
No Placebo Group
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.
12345How 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.
23467Eligibility 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.
+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.
+13 more
Trial 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
Participant Groups
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.
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
Research Locations NearbySelect from list below to view details:
Dana Farber Cancer InstituteBoston, MA
Johns Hopkins University Medical CenterBaltimore, MD
Brigham and Women's HospitalBoston, MA
Memorial Sloan Kettering Cancer CenterNew York, NY
More Trial Locations
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Who Is Running the Clinical Trial?
Dana-Farber Cancer InstituteLead Sponsor
National Institutes of Health (NIH)Collaborator
Candel Therapeutics, Inc.Industry Sponsor
References
Temozolomide resistant human brain tumor stem cells are susceptible to recombinant vesicular stomatitis virus and double-deleted Vaccinia virus in vitro. [2018]Malignant glioma still has a poor prognosis and remains incurable. Although temozolomide (TMZ) has demonstrated antitumor activity, its use recently has been halted because of some patients' resistance to this drug. New treatments are desperately needed. An oncolytic virus (virotherapy) is being developed as a novel cancer therapy. We have previously reported that recombinant Vesicular Stomatitis Virus (VSV-ΔM51) and double deleted Vaccinia Virus (vvDD) infected and killed glioma cell lines in vitro and prolonged survival in animal glioma models. As a proposed ex vivo test, the oncolytic potential of VSV-ΔM51 and vvDD in the established human brain tumor stem cells (BTSCs) and the differentiated cells from fresh brain tumor tissues in vitro were further investigated.
Immunovirotherapy for the Treatment of Glioblastoma and Other Malignant Gliomas. [2023]Glioblastoma multiforme (GBM) represents one of the most challenging malignancies due to many factors including invasiveness, heterogeneity, and an immunosuppressive microenvironment. Current treatment modalities have resulted in only modest effect on outcomes. The development of viral vectors for oncolytic immunovirotherapy and targeted drug delivery represents a promising therapeutic prospect for GBM and other brain tumors. A host of genetically engineered viruses, herpes simplex virus, poliovirus, measles, and others, have been described and are at various stages of clinical development. Herein we provide a review of the advances and current state of oncolytic virotherapy for the targeted treatment of GBM and malignant gliomas.
Oncolytic viruses: clinical applications as vectors for the treatment of malignant gliomas. [2023]Gene therapy using viral vectors for the treatment of primary brain tumors has proven to be a promising novel treatment modality. Much effort in the past has been placed in utilizing replication-defective viruses to this end but they have shown many disadvantages. Much recent attention has been focused on the potential of replication-competent viruses to discriminatingly target, replicate within, and destroy tumor cells via oncolysis, leaving adjacent post-mitotic neurons unharmed. The engineered tumor-selective herpes simplex-1 virus (HSV-1) mutants G207 and HSV1716 have completed Phase I investigations in the treatment of recurrent high-grade glioma. The results of these clinical trials are reviewed here. This review also aims to examine the manipulation and development of other viruses for the treatment of malignant glioma, including Newcastle disease virus, reovirus, poliovirus, vaccinia virus, and adenoviruses, in particular the adenovirus mutant ONYX-015.
[Oncolytic viruses for therapy of malignant glioma]. [2018]Effective treatment of malignant brain tumors is still an open problem. Location of tumor in vital areas of the brain significantly limits capasities of surgical treatment. The presence of tumor stem cells resistant to radiation and anticancer drugs in brain tumor complicates use of chemoradiotherapy and causes a high rate of disease recurrence. A technological improvement in bioselection and production of recombinant resulted in creation of viruses with potent oncolytic properties against glial tumors. Recent studies, including clinical trials, showed, that majority of oncolytic viruses are safe. Despite the impressive results of the viral therapy in some patients, the treatment of other patients is not effective; therefore, further improvement of the methods of oncolytic virotherapy is necessary. High genetic heterogeneity of glial tumor cells even within a single tumor determines differences in individual sensitivity of tumor cells to oncolytic viruses. This review analyses the most successful oncolytic virus strains, including those which had reached clinical trials, and discusses the prospects for new approaches to virotherapy of gliomas.
EXPLORING THE ANTITUMOR EFFECT OF VIRUS IN MALIGNANT GLIOMA. [2020]Malignant gliomas are the most common type of primary malignant brain tumor with no effective treatments. Current conventional therapies (surgical resection, radiation therapy, temozolomide (TMZ), and bevacizumab administration) typically fail to eradicate the tumors resulting in the recurrence of treatment-resistant tumors. Therefore, novel approaches are needed to improve therapeutic outcomes. Oncolytic viruses (OVs) are excellent candidates as a more effective therapeutic strategy for aggressive cancers like malignant gliomas since OVs have a natural preference or have been genetically engineered to selectively replicate in and kill cancer cells. OVs have been used in numerous preclinical studies in malignant glioma, and a large number of clinical trials using OVs have been completed or are underway that have demonstrated safety, as well as provided indications of effective antiglioma activity. In this review, we will focus on those OVs that have been used in clinical trials for the treatment of malignant gliomas (herpes simplex virus, adenovirus, parvovirus, reovirus, poliovirus, Newcastle disease virus, measles virus, and retrovirus) and OVs examined preclinically (vesicular stomatitis virus and myxoma virus), and describe how these agents are being used.
A mathematical approach to virus therapy of glioblastomas. [2019]It is widely believed that the treatment of glioblastomas (GBM) could benefit from oncolytic virus therapy. Clinical research has shown that Vesicular Stomatitis Virus (VSV) has strong oncolytic properties. In addition, mathematical models of virus treatment of tumors have been developed in recent years. Some experiments in vitro and in vivo have been done and shown promising results, but have been never compared quantitatively with mathematical models. We use in vitro data of this virus applied to glioblastoma.
Viruses in the treatment of brain tumors. [2019]The grave outlook for malignant glioma patients in spite of improvements to current modalities has ushered in new approaches to therapy. Viruses have emerged on the scene and gained attention for their ability to play essentially two roles: first, as vectors for therapeutic gene delivery and second, as engineered infectious agents capable of selectively lysing tumor cells. To date, clinical brain tumor trials using viruses for gene delivery have employed retroviral or adenoviral vectors to introduce ganciclovir susceptibility to tumors in the form of the HSV1-TK gene. Clinical oncolytic studies, on the other hand, have evaluated a conditionally replicating HSV as an antineoplastic agent. Despite some promise afforded by these trials, further studies are warranted; the investigation of additional viruses to play these roles is inevitable and is now precedented.