Combination of Immunization and Radiotherapy for Malignant Gliomas (InSituVac1)

Study Overview
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Brief Summary
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The study will investigate combined radiotherapy and immunotherapy on malignant gliomas. Immune adjuvants will be injected intratumorally and systemically to induce antitumor-specific immunity after radiation induced immunological tumor cell death (ICD). With radiation, tumor cells release tumor antigens that are captured by antigen presenting dendritic cells. Immune adjuvants promote the presentation of tumor antigens and the priming of antitumor T lymphocytes. The combined treatment induces and amplifies the specific antitumor immunity in patients with malignant gliomas, prolonging survivals of patients.

Detailed Description
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High grade gliomas, such as glioblatoma (GBM) is an aggressive malignancy with a poor prognosis. The current strategy for newly diagnosed GBM patients includes surgery, chemotherapy and radiotherapy. Unfortunately, after the standard treatmetn,the median survival of GBM is only about one year. Once relapsed, there is no standard therapy and survival is less than 9 months. Recently, personalized cancer immunotherapy has shown great promise in treating different types of cancers. However, effective immunotherapies for high grade gliomas, especially after progression, have yet to be established. Newly diagnosed GBM patients experience recurrence in five or seven months after standard treatment. We will investigate whether combining radiotherapy with intratumoral and systemic administration of immune adjuvants will improve the treatment outcome of high grade gliomas. We will use several immune adjuvants that activate innate and adaptive immunity.

Official Title
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Combination of Immunization and Radiotherapy for Malignant Gliomas (InSituVac1)

Conditions
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High Grade Glioma, Glioblastoma, Glioma of Brainstem, Glioma, Malignant

Intervention / Treatment
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* Combination Product: Combined immune adjuvants and radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathologically confirmed glioma Age18-65 Participants had undergone maximal surgical resection Amount of dexamethasone was not more than 2mg/ days Ability and willingness to sign informed consent Karnofsky Performance Score of 70 or more Normal liver and kidney function Not accepted other treatment plan during the immunotherapy Exclusion Criteria: Not conforming to the standard Systemic illness or medical condition may pose additional risk,including cardiac, incompensated renal or liver function abnormalities;inflammatory and immune system diseases of rheumatic arthritis Received other drugs for glioma therapy 60days before participated Allergy to immune adjuvant Nervous system disease and diffuse leptomeningeal disease Amount of dexamethasone was more than 2mg/days during the immunotherapy Pregnant or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined immune adjuvants and radiation<br>Patients with malignant gliomas will receive combined immune adjuvants (GM-CSF, TLR ligands) and radiation. The safety and efficacy will be analyzed. | Combination Product: Combined immune adjuvants and radiation<br>* 24 hours before the radiation, patients will be administrated poly I:C or CAR-T or TCR-T intratumorally and receive granulocyte macrophage colony stimulating factor 5 days after the radiation.<br>* Other names: TCR-T;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-related Adverse Events | Adverse events during and after the combined treatment | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Disease progression free survival time after combined treatment | 2 years | 
| Overall Survival | Overall survival time after the combined treatment | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gliomas, radiotherapy, immunetherapy