Glioblastoma MultiformePhase 1/2NCT06562621
Clinical Study on the Safety and Efficacy of Novel Oncolytic Virus in the Treatment of Recurrent Malignant Glioma
A Phase 1/2 study testing ON-01 and ONF in people with Glioblastoma Multiforme and Gliomas, Malignant, run by Beijing Neurosurgical Institute at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Glioblastoma Multiforme, Gliomas, Malignant
- What is being tested?
- ON-01 and ONF
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteChina
- Study dates
- 1 Aug 2018to 1 Mar 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.;
Show all 9Show fewer
- Patients with systemic autoimmune disease or immunodeficiency disease;
- Patients with severe allergies;
- Patients with chronic diseases requiring long-term immunologic preparation or glucocorticoid therapy.
Trial locations and contacts
1 site in 1 country.
About this study
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
- Being tested
- ON-01, ONF
- Medical subject headings
- Glioblastoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ON-01Biological
Also called Oncolytic virus, Herpes simplex virus
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.
ONFDrug
Also called Flucytosine, 5-FC, 5-Fluorocytosine
ONF is an extended-release formulation of flucytosine.
| Study group | Role | What they receive |
|---|---|---|
| ON-01/ONF | Experimental | ON-01: 1ml intratumoral injection of ON-01. ONF: 100 mg/kg/day orally after operation for 20 consecutive days. Receives: Biological: ON-01; Drug: ONF |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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.
Measured: 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.
Measured: from initial ON-01 administration to time of progression or death of any cause for up to 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2024
- Study start1 Aug 2018
- Primary completion1 Aug 2022
- Study completion1 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beijing Neurosurgical Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06562621
- Sponsor's protocol ID
- CFH2020-1-1071
- Status last verified
- Aug 2024
- First submitted
- 13 Aug 2024
- Last updated
- 20 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study on the Safety and Efficacy of Novel Oncolytic Virus in the Treatment of Recurrent Malignant Glioma
- ClinicalTrials.gov ID
- NCT06562621
- Acronym / sponsor ID
- CFH2020-1-1071
- Conditions
- Glioblastoma Multiforme, Gliomas, Malignant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Beijing Neurosurgical InstituteUniversity, hospital or other
- Study start
- 1 Aug 2018 (actual)
- Primary completion
- 1 Aug 2022 (actual)
- Study completion
- 1 Mar 2024 (actual)
- First posted
- 20 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ON-01/ONF | Experimental | Biological: ON-01, Drug: ONFON-01: 1ml intratumoral injection of ON-01. ONF: 100 mg/kg/day orally after operation for 20 consecutive days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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%;
Key exclusion criteria (9 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ON-01Also: Oncolytic virus, Herpes simplex virusON-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. | Biological | ON-01/ONF |
| ONFAlso: Flucytosine, 5-FC, 5-FluorocytosineONF is an extended-release formulation of flucytosine. | Drug | ON-01/ONF |
Primary outcome
Long term safety follow up
Time frame: From study entry up to 5 years
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.
2 secondary outcomes
Overall survival in days from the initial ON-01 administration on parent study to the date of death.
Time frame: 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.
Time frame: from initial ON-01 administration to time of progression or death of any cause for up to 5 years.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2024.
- Individual participant dataSharing planned: No
Related trials for Glioblastoma Multiforme
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ON-01 and ONF in people with Glioblastoma Multiforme and Gliomas, Malignant, run by Beijing Neurosurgical Institute at 1 site in China.
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 8 inclusion and 9 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: finished, as of the sponsor's last update on 20 Aug 2024. 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 China. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Long term safety follow up (time frame: From study entry up to 5 years). 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 Aug 2024.