Clinical Study on the Safety and Efficacy of Novel Oncolytic Virus in the Treatment of Recurrent Malignant Glioma
NCT Number: NCT06562621
Status: COMPLETED
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: Glioblastoma Multiforme|Gliomas, Malignant
Interventions: BIOLOGICAL: ON-01|DRUG: ONF
Sponsor: Beijing Neurosurgical Institute
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 38
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2018-08-01
Completion Date: 2024-03-01
Locations: Beijing Tiantan Hospital, Beijing, Beijing, 100050, China

Summary:
Glioma is the most common intracranial tumor. Among them, malignant glioma shows diffuse and infiltrating growth. Although it is given a comprehensive treatment such as surgery, radiotherapy and chemotherapy, it is prone to relapse, and there is an urgent need to explore new treatment methods. Oncolytic virus is currently the world's most cutting-edge treatment of glioma. On the basis of previous research on glioma and oncolytic virus (HSV-1), an engineered new oncolytic virus ON-01 containing CD gene has been constructed. In vitro and in vivo animal experiments have found that it has a good therapeutic effect on malignant glioma, and it has been approved by the ethics committee of Tiantan Hospital for its clinical research. This project intends to study the safety and effectiveness of ON-01 in the clinic on the basis of pre-clinical trials and preclinical research, clarify the oncolytic mechanism of ON-01 in the treatment of malignant glioma, and explore the dissolution of brain glioma. The new strategy of tumor virus treatment lays a theoretical foundation for the clinical promotion and application of ON-01 and product transformation.

Primary Outcome Measures: Long term safety follow up, The short-term adverse reactions of the subjects during hospitalization after receiving stereotactic injection of the oncolytic virus ON-01 will be recorded, and the incidence of these adverse reactions will be statistically analyzed. The short-term adverse reactions include: nausea, altered mental status, fever, pyramidal tract syndrome, flush face, epilepsy, anemia, leukopenia, thrombocytopenia, hyponatremia, hypokalemia, hypocalcemia, arrhythmia. These adverse reactions will be classified into four grades according to their severity. Within two weeks, a specialized neurosurgeon will conduct a clinical examination on the subjects to assess their motor, sensory, and language functions. Detailed post-injection treatment of each patient was recorded. Patients unwilling to accept or failed to complete the treatment due to safety or economic reasons were stratified as incomplete treatment group., From study entry up to 5 years
Secondary Outcome Measures: Overall survival in days from the initial ON-01 administration on parent study to the date of death., Overall survival (OS) defined as the duration from the date of stereotactic biopsy to the date of death or last follow up. At baseline, all patients underwent a thorough examination including blood cell counts, blood chemical analysis (including hepatic and renal function). Tumor sample of each patient was examined by 3 independent neuro-pathologists. Patients with the diagnosis other than recurrent GBM in paraffin section were excluded from the study. On the tenth day after injection, an enhanced MRI was carried out to evaluate tumor response. Tumor and residual tumor size was approximately estimated using the sum of the products of the largest perpendicular diameters of enhanced lesion. The clinical, operative, and hospitalization records were retrospectively reviewed. The Karnofsky Performance scale (KPS) score was used to describe patients' functional status., From initial ON-01 administration to death of last patient alive for up to 5 years.|Progression-free survival in days from the initial ON-01 administration on parent study to confirmed disease progression or death from any cause., Progression-free survival (PFS) refers to the length of time after a patient receives treatment with the oncolytic virus ON-01 during which the size of the glioma tumor either decreases or does not increase further on imaging. It is used as an indicator to assess the effectiveness of the oncolytic virus treatment. A longitudinal follow-up was planned for each patient at the following time points: the tenth day after injection, monthly thereafter, or whenever symptoms suggesting tumor relapse occurred. Each follow-up included an enhanced MRI to detect possible asymptomatic tumor recurrence and a blood test to find adverse events. Undetermined MRI scan were carefully reviewed by a senior neurosurgeon and neuroradiologist to differentiate tumor recurrence and radiation induced encephalic necrosis. If necessary, serial of MRI scans or positron emission tomography (PET) were performed., from initial ON-01 administration to time of progression or death of any cause for up to 5 years.