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.
• 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
• 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