AzTrials
AzTrials

Malignant Glioma of BrainPhase 1rQNestinNCT03152318

A Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2

A Phase 1 study testing rQNestin, Cyclophosphamide and Stereotactic biopsy in people with Malignant Glioma of Brain and Astrocytoma, run by Dana-Farber Cancer Institute at 5 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
rQNestin, Cyclophosphamide and Stereotactic biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
5 sitesUnited States
Study dates
18 Jul 2017to Jan 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Frozen biopsy consistent with glioma by neuropathologist at the time of the first surgery in this longitudinal trial. Biopsy confirmation of glioma or infiltrative glioma at time of surgery will be acceptable, provided the subject has prior pathology confirmation of IDH wild-type glioma. Patients with reactive changes, gliosis or normal brain tissue only, without evidence of glioma at initial study surgery only will not receive study rQNestin34.5v.2 therapy and will be replaced. Confirmation of glioma at subsequent neurosurgical procedures beyond the initial surgery will not be required.
  • Participants must have prior diagnosis of IDH wild-type glial tumor including GBM, grade 3 anaplastic astrocytoma or oligodendroglioma or or grade 2 astrocytoma with genetic features consistent with GBM, as confirmed by a neuropathologist or by a previous local pathology report. IDH wild-type designation may be based on negative immunohistochemistry (IDH1 R132H mutation) or next generation sequencing for patients with grade 4 tumor and by negative next-generation sequencing for those with grade 2 or 3 tumors. Patients with negative immunohistochemistry study for IDH1 R132H who are identified to have an alternative mutation of IDH1 or 2 are also not eligible.
  • Prior history of external beam radiotherapy ≥ 5,000 cGy delivered to the tumor at least 4 weeks prior to OHRS registration. Participants over the age of 70 with prior history of hypofractionated external beam radiotherapy will also be accommodated, in accordance with NCCN guidelines.
  • Prior history of temozolomide chemotherapy provided concurrent with external beam radiotherapy and after as per current standard of care. However, temozolomide is not required to have been provided concomitantly or after radiation if the patient had unmethylated MGMT promoter. At least 23 days must have passed from the last dose of temozolomide and first dose of rQNestin34.5v.2.
  • For use of other investigational drug or other anti-tumor treatment, the following time periods must have elapsed from the projected start of scheduled study treatment: 4 weeks or 5 half-lives (whichever is shorter) from any investigational agent; 4 weeks from cytotoxic therapy (except 23 days for TMZ; 6 weeks from last dose for nitrosoureas); 12 weeks from completion of prior radiation therapy; 6 weeks from antibodies treatment; 4 weeks or 5 half-lives (whichever is shorter) from other anti-tumor therapies; 1 day from NOVO-TTF (Optune®) or prior cancer vaccine therapy
  • The initial recurrent or residual gadolinium-enhancing lesion to be treated must be at least 1.0 cm in diameter and less than or equal to 2 cm in greatest maximal diameter, as determined by MRI. The initially treated lesion must be located in non-eloquent cortex, defined as non-dominant temporal, frontal, or occipital lobe. If located in the dominant cortex, the lesion must be in the occipital lobe. For lesions in dominant or non-dominant lobes, there should be a judgment that the subject will be able to tolerate multiple injections and biopsies, based on sufficient distance from the enhancing edge and eloquent cortex defined as speech (dominant mid-to posterior temporal lobe, parietal lobe and frontal lobe: Broca's area), memory (hippocampus and mesial dominant temporal lobe), or sensorimotor cortex. Subsequent injections (injections at day 15, 30, 60, 90, 120) will not be subject to the limitations of the initially treated lesion detailed above.
Show all 15Show fewer
  • Normal hematological, renal and liver function as defined below before first injection: ANC ≥ 1000/mcL, platelets ≥100,000/mcL, PT or PTT <1.5 x institutional upper limit, Hemoglobin >9.0 g/dL, Total serum bilirubin ≤ 1.5 upper normal institutional limits, AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal, and Serum creatinine ≤ 1.5 upper normal institutional limits OR Creatinine clearance ≥60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal.
  • Karnofsky Performance Score ≥70.
  • Age ≥ 18 years;
  • Ability to understand and the willingness to sign a written informed consent document;
  • The effects of rQNestin34.5v.2 and cyclophosphamide on the developing human fetus are unknown. For this reason and because cytotoxic \& immunomodulating agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation including 3 months following the study. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of study participation including 3 months following the study. Women of child-bearing potential must have a negative serum pregnancy test within 48 hours of study registration.
  • No dexamethasone therapy for at least 14 days prior to the first rQNestin34.5v.2 inoculation. Patients who are on physiologic doses of corticosteroids for the treatment of adrenal insufficiency will be allowed to enroll.
  • Ability to undergo MRI scanning with contrast;
  • Have residual tumor or be at first or second relapse. Note: Relapse is defined as progression following initial therapy (i.e., radiation ± chemotherapy). For participants who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse. Residual tumor is defined as contrast-enhancing tumor that is present after the initial surgery, radiation, and chemotherapy.
  • Participants must have recovered to grade 0 or 1 or pre-treatment baseline from clinically significant toxic effects of prior therapy (exceptions include but not limited to alopecia, laboratory values not listed per inclusion criteria, and lymphopenia which is common after therapy with temozolomide).

Who cannot join

  • Participants who exhibit any of the following conditions prior to initiating study treatment will not be eligible for this study:
  • Prior systemic malignancy requiring or expected to require more than surgical therapy within the past 24 months.
  • Known chronic infections with HIV, hepatitis B or C; participants with a history of resolved Hepatitis A may be included in the trial.
  • Participants with active viral, bacterial or fungal infection requiring concurrent antiviral or antibiotics.
  • Subjects with active HSV-1 infection on current valacyclovir, acyclovir or ganciclovir therapy must be off treatment with any of these agents at least 7 days prior to surgery.
  • Active, known, or suspected immunosuppressive disorders, such as acquired or congenital immune deficiency syndromes and autoimmune diseases.
Show all 17Show fewer
  • Unacceptable anesthesia risk
  • Pregnant or lactating females who are breastfeeding.
  • Participants who are receiving other investigational agents or immunotherapeutic agents during the period of rQNestin34.5v.2 longitudinal injections.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant active hepatic or renal disease, an active infection requiring systemic therapy, need for continuous systemic anticoagulation that cannot be stopped or psychiatric illness/social situations that would limit compliance with study requirements.
  • Certain tumor sizes and locations are exclusionary: Participants with tumor ≤ 1 cm proximity to the ventricles will be allowed to enroll. However the study agent (rQNestin34.5v.2) may not be injected in any area that could lead to spillage into the ventricles regardless of where the tumor is located; Participants whose initial tumor size, location and rate of growth are deemed by the treating neurosurgeons and the CAC to not be able to tolerate the time period of expected longitudinal injections with biopsies, which could be as short as 15 days and as long as 120 days. This category would include tumors located in: a) dominant and non-dominant locations close to eloquent cortices (sensorimotor strip, speech and memory cortices), b) deep nuclear structures (caudate, putamen, thalamus), c) close proximity to corticospinal tracts (based on consensus of Clinical Advisory Committee); Participants with multifocal or multicentric tumors or tumors arising in the brain stem or spinal cord or diffuse leptomeningeal disease.
  • Has received systemic immunosuppressive treatments, aside from systemic corticosteroids (such as methotrexate, chloroquine, azathioprine, etc.) within six months of registration.
  • Has received anti-VEGF or anti-VEGFR targeted agents (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc.)
  • Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of registration.
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Has gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE Grade > 3 within 6 months of registration.
  • Requires systemic anti-coagulation that cannot be halted for each intraoperative and peri-operative biopsy time period.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Johns Hopkins University Medical Center

    Baltimore, Maryland, 21287

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02215

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase I Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2, a Genetically Engineered HSV-1 Virus, and Immunomodulation With Cyclophosphamide

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.

Read the detailed description

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. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved rQNestin34.5v.2 as a treatment for any disease. This is the first time that rQnestin34.5v.2 will be given to humans.

The research drug, rQNestin34.5v.2, is an oncolytic viral vector made from the herpes simplex virus type 1 (HSV1). The large majority of humans already have regular HSV1 in their nervous system. Normally, this virus can cause cold sores in areas like the lips, fingers and genitals in humans by making copies of itself in normal healthy cells. In some cases, HSV1 can cause severe infection of the brain and liver and/or death. However, scientists have removed or changed parts of the rQNestin virus being used on this study so it can only make copies of itself in glioma cells and not normal healthy cells.

If it is effective, the rQNestin34.5v.2 drug will spread to a glioma cell, kill it, and then make a copy of itself and spread again. This should be repeated over and over until all glioma cells are reached. If rQNestin34.5v.2 moves into a normal brain cell, it should not grow and make copies, and therefore should not spread to other normal brain cells.

The purpose of this research study is to test if rQnestin34.5v.2 is safe to use in humans, and if it is effective in treating malignant glioma. This study is also looking for the highest dose of rQNestin34.5v.2 that can be given safely to people with malignant brain tumors.

Being tested
rQNestin, Cyclophosphamide, Stereotactic biopsy
Keywords
Malignant Glioma, Brain Tumor, Glioblastoma, CAN-3110
Medical subject headings
Astrocytoma, Oligodendroglioma, Disease, Ependymoma, Ganglioglioma, Brain Neoplasms, Glioma, Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rQNestinDrug

    Also called rQNestin34.5v.2, CAN-3110

    rQNestin is an oncolytic viral vector. It is administered via intratumoral injection during biopsy surgery.

  • CyclophosphamideDrug

    Also called Cytoxan®, Neosar®

    Cyclophosphamide is an immunomodulating agent. It is administered intravenously in a single dose 2 days (+/- 6 hrs) before surgery.

  • Stereotactic biopsyProcedure or surgery

    In both arms, subjects will undergo standard of care stereotactic biopsy in the intraoperative MRI operating room. The stereotactic needle will be placed stereotactically into the tumor bed using intraoperative MRI guidance to collect the biopsy, and again to administer the rQNestin oncolytic virus.

Study groups in NCT03152318
Study groupRoleWhat they receive
Arm A- rQNestinExperimentalArm 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
Receives: Drug: rQNestin; Procedure: Stereotactic biopsy
Arm B- rQNestin+CPAExperimentalArm 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
Receives: Drug: rQNestin; Drug: Cyclophosphamide; Procedure: Stereotactic biopsy
Arm C- Multiple Dose rQNestinExperimentalArm 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.
Receives: Drug: rQNestin; Procedure: Stereotactic biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose

    The primary objective is to determine the maximum tolerated dose of rQNestin34.5v.2 injected into recurrent malignant gliomas, with or without previous immunomodulation with cyclophosphamide.

    Measured: Minimum of 21 Days

Secondary outcomes (6)

  1. MRI Changes in Permeability

    Determine MRI alterations of permeability in injected sites using standard perfusion sequences.

    Measured: Evaluated every 2 months for 1 year

  2. MRI Changes in Volume

    Determine MRI alterations of cerebral blood volume in injected sites using standard sequences.

    Measured: Evaluated every 2 months for 1 year

  3. MRI Changes in Flow

    Determine MRI alterations of cerebral blood flow in injected sites using standard sequences.

    Measured: Evaluated every 2 months for 1 year

  4. Viral Shedding in Saliva

    Assess the shedding of rQNestin34.5v.2 in the saliva of subjects treated with rQNestin34.5v.2

    Measured: Evaluated up to day 56 for each subject

  5. HSV1 Viremia

    Assess the degree of HSV-1 viremia post rQNestin34.5v.2 administration

    Measured: Evaluated up to day 56 for each subject

  6. HSV1 Antibody Response

    Identify changes in HSV1 antibody response

    Measured: Evaluated up to day 56 for each subject

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 May 2017
  2. Study start18 Jul 2017
  3. Primary completionJan 2027 (estimated)
  4. Study completionJan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Phase I, open-label, single center, dose-escalation, triple-arm clinical trial of an oncolytic virus called rQNestin
Masking
None (open label)
Enrolment
62 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03152318
Sponsor's protocol ID
16-557
Acronym
rQNestin
Status last verified
Mar 2026
First submitted
9 May 2017
Last updated
4 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Meylan M, Tian Y, Wu L, Ling AL, Kovarsky D, Barlow GL, Nguyen LD, Pyrdol J, Marx S, Westphal L, Michel J, Gonzalez Castro LN, Dumont S, Santos A, Tirosh I, Suva ML, Chiocca EA, Wucherpfennig KW. Persistent T cell activation and cytotoxicity against glioblastoma following single oncolytic virus treatment in a clinical trial. Cell. 2026 Mar 5;189(5):1287-1304.e18. doi: 10.1016/j.cell.2025.12.055. Epub 2026 Feb 11.

    PubMed 41679299

  • Noh MH, Kang JM, Miller AA, Nguyen G, Huang M, Shim JS, Bueso-Perez AJ, Murphy SA, Rivera-Caraballo KA, Otani Y, Kim E, Yoo SH, Yan Y, Banasavadi-Siddegowda Y, Nakashima H, Chiocca EA, Kaur B, Zhao Z, Lee TJ, Yoo JY. Targeting IGF2 to reprogram the tumor microenvironment for enhanced viro-immunotherapy. Neuro Oncol. 2024 Sep 5;26(9):1602-1616. doi: 10.1093/neuonc/noae105.

    PubMed 38853689

  • Ling AL, Solomon IH, Landivar AM, Nakashima H, Woods JK, Santos A, Masud N, Fell G, Mo X, Yilmaz AS, Grant J, Zhang A, Bernstock JD, Torio E, Ito H, Liu J, Shono N, Nowicki MO, Triggs D, Halloran P, Piranlioglu R, Soni H, Stopa B, Bi WL, Peruzzi P, Chen E, Malinowski SW, Prabhu MC, Zeng Y, Carlisle A, Rodig SJ, Wen PY, Lee EQ, Nayak L, Chukwueke U, Gonzalez Castro LN, Dumont SD, Batchelor T, Kittelberger K, Tikhonova E, Miheecheva N, Tabakov D, Shin N, Gorbacheva A, Shumskiy A, Frenkel F, Aguilar-Cordova E, Aguilar LK, Krisky D, Wechuck J, Manzanera A, Matheny C, Tak PP, Barone F, Kovarsky D, Tirosh I, Suva ML, Wucherpfennig KW, Ligon K, Reardon DA, Chiocca EA. Clinical trial links oncolytic immunoactivation to survival in glioblastoma. Nature. 2023 Nov;623(7985):157-166. doi: 10.1038/s41586-023-06623-2. Epub 2023 Oct 18.

    PubMed 37853118

  • Otani Y, Yoo JY, Lewis CT, Chao S, Swanner J, Shimizu T, Kang JM, Murphy SA, Rivera-Caraballo K, Hong B, Glorioso JC, Nakashima H, Lawler SE, Banasavadi-Siddegowda Y, Heiss JD, Yan Y, Pei G, Caligiuri MA, Zhao Z, Chiocca EA, Yu J, Kaur B. NOTCH-Induced MDSC Recruitment after oHSV Virotherapy in CNS Cancer Models Modulates Antitumor Immunotherapy. Clin Cancer Res. 2022 Apr 1;28(7):1460-1473. doi: 10.1158/1078-0432.CCR-21-2347.

    PubMed 35022322

  • Chiocca EA, Nakashima H, Kasai K, Fernandez SA, Oglesbee M. Preclinical Toxicology of rQNestin34.5v.2: An Oncolytic Herpes Virus with Transcriptional Regulation of the ICP34.5 Neurovirulence Gene. Mol Ther Methods Clin Dev. 2020 Mar 30;17:871-893. doi: 10.1016/j.omtm.2020.03.028. eCollection 2020 Jun 12.

    PubMed 32373649

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing rQNestin, Cyclophosphamide and Stereotactic biopsy in people with Malignant Glioma of Brain and Astrocytoma, run by Dana-Farber Cancer Institute at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (time frame: Minimum of 21 Days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03152318, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in