Clinical Study on the Safety and Efficacy of Novel Oncolytic Virus in the Treatment of Recurrent Malignant Glioma

NCT06562621 | Completed Phase 1 DMC

• 1 other identifier: CFH2020-1-1071
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glioblastoma Multiforme; Gliomas, Malignant

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Overall survival in days from the initial ON-01 administration on parent study to the date of death.

  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.

  from initial ON-01 administration to time of progression or death of any cause for up to 5 years.

Study Arms (1)

ON-01/ONF

EXPERIMENTAL

ON-01: 1ml intratumoral injection of ON-01. ONF: 100 mg/kg/day orally after operation for 20 consecutive days.

Biological: ON-01; Drug: ONF

Interventions

ON-01 BIOLOGICAL

ON-01 consists of a yeast cytosine deaminase (CD) gene. The CD gene converts the antifungal 5-flurocytosine (5-FC) to the anticancer drug 5-FU in cells that have been infected by ON-01.

Also known as: Oncolytic virus, Herpes simplex virus

ON-01/ONF

ONF DRUG

ONF is an extended-release formulation of flucytosine.

Also known as: Flucytosine, 5-FC, 5-Fluorocytosine

ON-01/ONF

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients has given written informed consent；
• Age is between 18 years old and 75 years old, inclusive;
• Patients must have histologically or cytologically confirmed Glioblastoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligodendrocyte-glioma;
• Residual lesion must be ≥1.0 cm in diameter as determined by MRI;
• Karnofsky Performance Status ≥70%;
• Patients must have normal organ and marrow function. Absolute neutrophil count: ≥ 1,500/mm3, Hemoglobin\>10 g/dL platelets: \>100,000/mm3, total bilirubin\< 1.5 ×ULN; AST(SGOT)(aspartate aminotransferase)/ALT(SGPT)(alanine aminotransferase): \<2.5 X institutional upper limit of normal; Serum creatinine \< 1.5 ×ULN, and normal heart function;
• Good compliance: can actively cooperate with doctors' treatment and follow-up survey;
• Females of childbearing potential must not be pregnant; this will be confirmed by a negative serum pregnancy test within 7 days prior to starting study treatment and must use a birth control method in addition to barrier methods (condoms).

You may not qualify if:

• Pregnant or lactating women;
• Prior history of encephalitis, multiple sclerosis, or other CNS infection;
• Herpes simplex virus infection active period;
• Patients with a history of organ transplantation or waiting for an organ transplant;
• Uncontrollable infectious diseases or other serious diseases such as HIV positive;
• Severe pulmonary, cardiac or other systemic disease, specifically: Including active infections, uncontrolled high blood pressure, unstable angina pectoris, angina pectoris that began to develop within the last 3 months, congestive heart failure, myocardial infarction that occurred within the first 12 months of enrollment, requiring serious;medical treatment Arrhythmia, liver, kidney failure, etc.;
• Patients with systemic autoimmune disease or immunodeficiency disease;
• Patients with severe allergies;
• Patients with chronic diseases requiring long-term immunologic preparation or glucocorticoid therapy.

Sponsors & Collaborators

• Beijing Neurosurgical Institute: lead

Study Sites (1)

Beijing Tiantan Hospital

Beijing, Beijing Municipality, 100050, China

Location

MeSH Terms

Conditions

Glioblastoma; Glioma

Interventions

Oncolytic Virotherapy; Flucytosine

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Cytosine; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2024
• First Posted: August 20, 2024
• Study Start: August 1, 2018
• Primary Completion: August 1, 2022
• Study Completion: March 1, 2024
• Last Updated: August 20, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)