NCT06177964

Lerapolturev (PVSRIPO) in GBM

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 92 (estimated)
• Sponsor: Darell Bigner · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 adult patients diagnosed with recurrent glioblastoma at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke.

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.

Conditions

• Recurrent Supratentorial Glioblastoma

Interventions

Type	Name	Description
DRUG	Lerapolturev	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.
DRUG	Lomustine Pill	Lomustine will be given as a single oral dose of 110 mg/m2 every six weeks for up to 9 cycles.

Timeline

• Start date: 2024-07-15
• Primary completion: 2029-02-01
• Completion: 2029-02-01
• First posted: 2023-12-20
• Last updated: 2025-08-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study