Combination of Stereotactic Radiosurgery and Enhanced Immunotherapy for Recurrent Glioblastomas(inSituVac2)(CSREIG)

Study Overview
=================
Brief Summary
-----------------
The study will investigate combined stereotactic radiosurgery and enhanced immunotherapy for recurrent glioblastomas. 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 recurrent glioblastomas, prolonging survivals of patients.

Detailed Description
-----------------
Recurrent glioblatoma (rGBM) is an aggressive malignancy with a poor prognosis. 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 rGBMs have yet to be established. The last clinical trial (inSituVac1) showed promised results and this study was based on it. We will investigate whether combining stereotactic radiosurgery with intratumoral and systemic administration of enhanced immune adjuvants will improve the treatment outcome of rGBMs. We will use several immune adjuvants that activate innate and adaptive immunity.

Official Title
-----------------
Combination of Stereotactic Radiosurgery and Enhanced Immunotherapy for Recurrent Glioblastomas (inSituVac2)(CSREIG)

Conditions
-----------------
Recurrent Glioblastoma

Intervention / Treatment
-----------------
* Combination Product: Combined stereotactic radiosurgery and enhanced immunotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Histopathologically confirmed rGBM 2. Age18-65 3. Participants had undergone maximal surgical resection 4. Amount of dexamethasone was not more than 2mg/ days 5. Ability and willingness to sign informed consent 6. Karnofsky Performance Score of 70 or more 7. Normal liver and kidney function 8. Not accepted other treatment plan during the immunotherapy Exclusion Criteria: 1. Not conforming to the standard 2. 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 3. Received other drugs for glioma therapy 60 days before participated 4. Allergy to immune adjuvant 5. Nervous system disease and diffuse leptomeningeal disease 6. Amount of dexamethasone was more than 2mg/days during the immunotherapy 7. Pregnant or lactation

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rGBM Group with combined stereotactic radiosurgery and enhanced immunotherapy<br>Patients with rGBMs will receive combined stereotactic radiosurgery and enhanced immunal adjuvants (GM-CSF, Sapylin, MnCl2). The safety and efficacy will be analyzed. | Combination Product: Combined stereotactic radiosurgery and enhanced immunotherapy<br>* Patients will be administrated immunal adjuvants intratumorally and systemically with concurrent stereotactic radiosurgery.<br>* Other names: stereotactic radiosurgery and GM-CSF, Sapylin, MnCl2;|
| No Intervention: rGBM Group with<br>After biopsy or tumor resection, this rGBM group was treated with FDA-approved strategies proposed by the MDT group. | |

What is the study measuring?
-----------------
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 | 
| Progression-free Survival | Disease progression free survival time after combined treatment | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | Overall survival time after the combined treatment | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent glioblastomas, stereotactic radiosurgery, enhanced immunotherapy