Personalized Cellular Vaccine for Brain Metastases (PERCELLVAC3)

Study Overview
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Brief Summary
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Cancer patients with brain metastases (BM) have poor prognosis. Current treatments produce limited efficacy. Recent advance in cancer immunotherapy has provided important new means to treat cancer patients at advanced stages. This study is designed to perform a clinical trial to treat advanced caner patients with brain metastases with personalized dendritic cell-based cellular vaccines. The patients will receive vaccines consisting of mRNA tumor antigen pulsed DCs. Immune response to the immunized tumor antigens will be monitored. Safety and efficacy will be observed in this study.

Detailed Description
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This is an open label, single-arm, single-institution, Phase I study designed to investigate the safety and efficacy of personalized cellular tumor vaccines for cancer patients with brain metastases (BM). BM patients will undergo tumor resection or biopsy and the tumor tissues will be analyzed for the expression of tumor antigens and immune-related genes. The patients will be immunized with DCs pulsed with mRNA encoded tumor antigens. Patients will be immunized with DC vaccines on a biweekly basis. Safety and efficacy will be monitored. The objective of this study is to assess the safety of the personalized cellular vaccines and to deterimine the antitumor specific T cell responses. The efficacy of the vaccines will be determined using RANO-BM criteria, progression-free survival and overall survival.

Official Title
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Personalized Cellular Vaccine Therapy in Treating Patients With Brain Metastases From Solid Tumors

Conditions
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Brain Cancer, Neoplasm Metastases

Intervention / Treatment
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* Biological: Personalized cellular vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Solid tumor with brain metastases. Patients at the age of 18-65. Patients undergo tumor resection or biopsy. Patients with Karnofsky scores > or =70 Patients with normal range of hematologic and metabolic test results. Patients must have no corticosteroids treatment at least one week before vaccination. Patients capable of understanding the study and signed informed consent. Exclusion Criteria: Infectious diseases HIV, HBV, HCV. Documented immunodeficiency. Documented autoimmune disease. Breast feeding females. Pregnant women. Any serious or uncontrolled medical or psychiatric conditions, for example, severe pulmonary, cardiac or other systemic disease. Patient inability to participate as determined by PI discretion.

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: Personalized cellular vaccine<br>Patients will undergo tumor resection or biopsy, and receive biweekly cellular vaccines consisting of mRNA-pulsed autologous DCs. | Biological: Personalized cellular vaccine<br>* Cancer patients with brain metastases will undergo tumor resection or biopsy, and receive tumor antigen mRNA pulsed cellular vaccines. Other Names: • Tumor antigen pulsed DC and PBMC, autologous tumor vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events and severe adverse events (safety and tolerability) | Incidence of adverse events and severe adverse events to measure safety and tolerability of mRNA-TAA pulsed autologous DC vaccines. | 3 years since the beginning of the first vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antitumor specific T cell response | The frequency of the peripheral CD8+ and CD4+ T cell response to the vaccine will be measured. | 4 weeks after the last vaccine | 
| Progression-free survival | Progression-free survival will be monitored for 2 year | 24 months since the beginning of the first vaccine | 
| Overall survival | Overall survival will be monitored for 3 years | 3 years since the beginning of the first vaccine | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid tumors, Brain metastases, DC vaccine, Personalized vaccine, Tumor antigens