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Recurrent Supratentorial GlioblastomaPhase 2NCT06177964

Lerapolturev (PVSRIPO) in GBM

A Phase 2 study testing Lerapolturev and Lomustine Pill in people with Recurrent Supratentorial Glioblastoma, run by Darell Bigner at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The purpose of this research study is to determine the safety and efficacy of administering two doses of lerapolturev in residual disease (within tumor margins) after surgery, followed later by repeated injections of lerapolturev in the subcutaneous area (under the skin) around the lymph nodes of the head and neck for… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent Supratentorial Glioblastoma
What is being tested?
Lerapolturev and Lomustine Pill
Could I receive a placebo?
No, everyone receives an active treatment
How many people
92 participants
Where
1 siteUnited States
Study dates
15 Jul 2024to Feb 2029
Phase
Phase 2
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

  • Age ≥ 18 years old at the time of entry into the study.
  • Histopathologically confirmed recurrent supratentorial glioblastoma (WHO grade 4) (high grade glioma with molecular features of glioblastoma will be eligible).
  • Karnofsky Performance Score (KPS) ≥ 70%
  • Hemoglobin ≥ 9 g/dl prior to biopsy
  • Platelet count ≥ 100,000/µl unsupported is necessary for eligibility on the study; however, because of risks of intracranial hemorrhage with catheter placement, platelet count ≥ 125,000/µl is required for the patient to undergo biopsy and catheter insertion, which can be attained with the help of platelet transfusion.
  • Neutrophil count ≥ 1000 prior to biopsy
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  • Creatinine ≤ 1.5 x normal range prior to biopsy
  • Total bilirubin ≤ 1.5 x ULN prior to biopsy (Exception: Participant has known or suspected Gilbert's Syndrome for which additional lab testing of direct and/or indirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.)
  • AST/ALT ≤ 2.5 x ULN
  • Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy. Patients with prior history of thrombosis/embolism are allowed to be on anticoagulation, understanding that anticoagulation will be held in the perioperative period per the neurosurgical team's recommendations. Low molecular weight heparin (LMWH) is preferred. If a patient is on warfarin, the international normalized ratio (INR) is to be obtained and value should be below 2.0 prior to biopsy.
  • At the time of biopsy, prior to administration of the 1st infusion of lerapolturev via CED, the presence of recurrent tumor must be confirmed by histopathological analysis.
  • Able to undergo brain MRI with and without contrast
  • Prior CDC-recommended vaccination series against PV and has received a boost immunization with trivalent Poliovirus Vaccine Inactivated (IPOL®) (Sanofi-Pasteur SA) at least 1 week, but less than 6 weeks, prior to administration of lerapolturev. Note: Patients who are unsure of their prior vaccination status must provide evidence of anti-PV immunity prior to enrollment, as applicable.
  • Patient or partner(s) meets one of the following criteria:
  • Non-childbearing potential (i.e., not sexually active, physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile, or any male who has had a vasectomy). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Postmenopausal for purposes of this study is defined as 1 year without menses.; or
  • Childbearing potential and agrees to use one of the following methods of birth control: approved hormonal contraceptives (e.g. birth control pills, patches, implants, or infusions), an intrauterine device, or a barrier method of contraception (e.g., a condom or diaphragm) used with spermicide.
  • A signed informed consent form approved by the Institutional Review Board (IRB) will be required for patient enrollment into the study. Patients must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study

Who cannot join

  • Females who are pregnant or breast-feeding
  • Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate
  • Patients with severe, active co-morbidity, defined as follow:
  • Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax > 99.5°F/37.5°C)
  • Patients with known immunosuppressive disease or known human immunodeficiency virus infection
  • Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4)
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  • Patients with known lung (forced expiratory volume in the first second of expiration (FEV1) < 50%) disease or uncontrolled diabetes mellitus
  • Known albumin allergy
  • History of agammaglobulinemia
  • Patients may not have received chemotherapy or bevacizumab ≤ 4 weeks [except for nitrosourea (6 weeks), or metronomic dosed chemotherapy such as daily etoposide or cyclophosphamide (1 week)] prior to starting the study drug unless patients have recovered from side effects of such therapy
  • Patients may not have received immunotherapy ≤ 4 weeks prior to starting the study drug unless patients have recovered from side effects of such therapy
  • Patients may not have received treatment with tumor treating fields (e.g., Optune®) ≤ 1 week prior to starting the study drug
  • Patients may not be less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation
  • Patients who have not completed all standard of care treatments, including surgical procedure and radiation therapy (Please note: For patients under 65 years old, standard radiation therapy is typically at least 59 Gy in 30 fractions over 6 weeks. For patients 65 years or older, standard RT is often reduced to a minimum 40 Gy in 15 fractions over 3 weeks.)
  • If the MGMT promoter in their tumor is known to be unmethylated, patients are not mandated to have received chemotherapy prior to participating in this trial
  • If the MGMT promoter in their tumor is known to be methylated or the MGMT promoter methylation status is unknown at time of screening, patients must have received at least one chemotherapy regimen prior to participating in this trial
  • Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord; radiological evidence of active (growing) disease (active multifocal disease); extensive subependymal disease (tumor touching subependymal space is allowed); tumor crossing the midline or leptomeningeal disease
  • Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to the 1st lerapolturev infusion via CED
  • Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
  • Patients with prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
  • Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months
  • Patients with known history of hypersensitivity to lomustine, dacarbazine, or any components of lomustine

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Madison Shoaf, MD contact

919-684-5301

dukebrain1@dm.duke.edu

United States1 site, 1 recruiting
  • Duke University Medical Center

    Durham, North Carolina, 27710

    Madison Shoaf, MD, 919-684-5301, dukebrain1@dm.duke.edu

    Stevie Threatt, 919-684-5301, dukebrain1@dm.duke.edu

    Recruiting

Other trials in United States

About this study

Official title: Randomized Phase 2 Clinical Trial of Repeated Intratumoral and Cervical Perilymphatic Lerapolturev Injections Versus Lomustine in Recurrent Glioblastoma (GBM)

The purpose of this research study is to determine the safety and efficacy of administering two doses of lerapolturev in residual disease (within tumor margins) after surgery, followed later by repeated injections of lerapolturev in the subcutaneous area (under the skin) around the lymph nodes of the head and neck for adult patients diagnosed with recurrent glioblastoma at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke.

Read the detailed description

The study will be conducted in two stages: Approximately twelve patients with recurrent supratentorial glioblastoma will enroll in stage 1.

Stage 1 is a safety lead-in which will assess the safety of lerapolturev when infused twice, 4 days apart, via Convection Enhanced Delivery (CED) in the residual disease of recurrent Glioblastoma (GBM) patients following maximal safe resection of the enhancing/necrotic portion of the disease recurrence.

A tissue biopsy of the area infused will be recommended 5 weeks (± 1 week) after the 2nd lerapolturev infusion via CED, if imaging changes suggest tumor progression vs. immune effect on the MRI obtained 4-5 weeks after the 2nd lerapolturev infusion via CED.

Stage 2 is a Phase 2 randomized clinical trial to compare the efficacy and safety of two treatment regimens for recurrent GBM patients who undergo maximal safe resection for their recurrence. Approximately eighty patients with recurrent supratentorial glioblastoma will enroll in stage 2 of the study.

Stage 2 has 2 arms and is randomized, like the flip of a coin. Arm 1 is Lerapolturev and Arm 2 is Lomustine. After the recurrent tumor has been removed by surgery, subjects will be randomly assigned to receive either the FDA-approved chemotherapy (lomustine) or the study drug (lerapolturev). Subjects receive lerapolturev infused in the residual disease via CED twice, 4-day apart. About 1 week after the 2nd lerapolturev infusion, subjects will start subcutaneous (under the skin) injections of lerapolturev into the area of the cervical lymph nodes (head and neck) nearest to their tumor weekly for 4 weeks and afterward every 3 weeks for about a year.

Subjects assigned to receive lomustine will begin taking it 3-4 weeks after surgery to remove their recurrent tumor. One prescribed dose of lomustine will be taken no more than once every 6 weeks, for no more than 1 year or up to 9 cycles.

Subjects will be followed for serious adverse events (side effects) for 30 days after stopping the study. Subjects' medical records will be reviewed for the remainder of their life, in order to collect data on subsequent treatments, disease progression, tumor size/volume, and survival.

There are risks to the study drug, lerapolturev, and the chemotherapy drug, lomustine. The most common risks of lerapolturev are headache, seizure, weakness on one side of the body, difficulty thinking or processing, difficulty receiving or responding to sensory information, fatigue, and difficulty speaking or comprehending. Risks associated with infusion procedure include mild discomfort at the infusion site, bleeding in the brain, pain, infection, and swelling of the brain. The study drug and procedures used together could also potentially cause more serious side effects. The most common risks of lomustine are changes in your red blood cell count, changes in platelets, changes in your liver, feeling confused and tired, poor appetite, and loss of ability to conceive or father a child.

Being tested
Lerapolturev, Lomustine Pill
Keywords
Lerapolturev, PVSRIPO, Lomustine, Shoaf, Glioblastoma, Glioma, Pro00113584, Duke, Istari Oncology, Intratumoral injection, Cervical Perilymphatic injection
Medical subject headings
Glioblastoma, Glioma

What participants receive

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

  • LerapolturevDrug

    Lerapolturev (intratumoral) will be dosed at 2x108 TCID50 in 3.0 mL x 2 doses (total dose 4x108 TCID50) by Convection Enhanced Delivery.

    For the patients randomized to the lerapolturev Arm 1 of Stage 2, seven days (±2 days) following completion of the 2nd intratumoral infusion of lerapolturev, patients will begin cervical perilymphatic subcutaneous injection of lerapolturev at a dose of 2 x 108 TCID50 (in 0.5 ml diluent) around the cervical lymph node chain ipsilateral to the intracranial tumor.

  • Lomustine PillDrug

    Lomustine will be given as a single oral dose of 110 mg/m2 every six weeks for up to 9 cycles.

Study groups in NCT06177964
Study groupRoleWhat they receive
Lerapolturev Arm (Stage 1)ExperimentalLerapolturev (intratumoral) will be dosed by Convection Enhanced Delivery (CED), infused twice, 4 days apart, in the remaining disease of recurrent Glioblastoma (rGBM) subjects following maximal safe resection of the disease recurrence. To assess treatment response and/or immunologic responses in the brain, a tissue biopsy of the area infused will be recommended 5 weeks (± 1 week) after the 2nd lerapolturev infusion via CED, in the event that changes suggestive of tumor progression are seen on the MRI obtained 4-5 weeks after the 2nd lerapolturev infusion via CED. .
Receives: Drug: Lerapolturev
Lerapolturev Arm (Stage 2 - Arm 1)ExperimentalLerapolturev (intratumoral) will be given by Convection Enhanced Delivery (CED), infused twice, 4 days apart, in the remaining disease of recurrent Glioblastoma (rGBM) subjects following maximal safe resection of their disease recurrence. This will be followed by subcutaneous injections of lerapolturev in the cervical perilymphatic (CPL) area on the same side as their tumor, weekly for 4 weeks and afterward every 3 weeks for about a year.
Receives: Drug: Lerapolturev
Lomustone (Stage 2 Arm 2)Active comparatorFollowing maximal safe resection of their tumor recurrence subjects will receive Lomustine as a single oral dose of 110 mg/m2 every six weeks for up to 9 cycles.
Receives: Drug: Lomustine Pill

What is being measured

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

  1. Proportion of patients at each dose level who experienced a dose-limiting toxicity - Stage 1

    Dose-limiting toxicities (DLTs) are defined as any of the following events that are possibly, probably, or definitely attributable to study treatment (i.e., lerapolturev) during dose escalation (Stage 1):

    • Any Grade 3 or any Grade 4 toxicity within 2 weeks, including cerebral edema or worsening neurologic symptoms
    • Any life-threatening event within 2 weeks
    • Treatment-related death at least possibly, probably, or definitely attributable to study treatment
    • Any grade 2 or higher serious cytokine release syndrome at least possibly, probably, or definitely attributable to study treatment, particularly those affecting vital organs (e.g., cardiac, hepatic, renal, CNS) occurring within 2 weeks of the infusion

    Measured: Up to 1 year

  2. Proportion of patients who experience an unacceptable toxicity - Stage 2

    Unacceptable toxicity is defined as any of the following events that are possibly, probably, or definitely attributable to study treatment:

    • Any Grade 3 or any Grade 4 toxicity within 2 weeks, including cerebral edema or worsening neurologic symptoms
    • Any life-threatening event within 2 weeks
    • Treatment-related death at least possibly, probably, or definitely attributable to study treatment
    • Any grade 2 or higher serious cytokine release syndrome at least possibly, probably, or definitely attributable to study treatment, particularly those affecting vital organs (e.g., cardiac, hepatic, renal, CNS) occurring within 2 weeks of the infusion

    Measured: Up to 1 year

  3. Overall survival (OS) - Stage 2

    Median OS, where OS is defined as the time between randomization and death

    Measured: 2 years

Secondary outcomes (1)
  1. Progression free survival (PFS)

    Median PFS, where PFS is defined as the time between randomization and initial failure (disease progression or death)

    Measured: 2 years

Timeline

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

  1. First posted20 Dec 2023
  2. Study start15 Jul 2024
  3. Primary completionFeb 2029 (estimated)
  4. Study completionFeb 2029 (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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
92 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06177964
Sponsor's protocol ID
Pro00113584
Status last verified
Jul 2026
First submitted
11 Dec 2023
Last updated
20 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lerapolturev and Lomustine Pill in people with Recurrent Supratentorial Glioblastoma, run by Darell Bigner at 1 site 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 17 inclusion and 22 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: looking for participants now, as of the sponsor's last update on 20 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Contact Madison Shoaf, MD (919-684-5301, dukebrain1@dm.duke.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of patients at each dose level who experienced a dose-limiting toxicity - Stage 1 (time frame: Up to 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 20 Jul 2026.

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