In this study, the investigators provide a combined treatment of personalized tumor neoantigen-loaded DC vaccine and conventional third-line therapy to patients with colorectal cancer (CRC) progressed after second-line treatment. The investigators observe the objective response rate (ORR), disease control rate (DCR), adverse event (AE), serious adverse event (SAE), progression-free survival (PFS), and overall survival (OS) , aiming to evaluate the effectiveness and safety of the treatment.
This study is conducted in accordance with the Declaration of Helsinki and the guidelines of the Consolidated Standards of Reporting Trials. 10 patients with CRC progressed after second-line therapy will be recruited in this study. With doctor's assessment, a combined treatment of conventional third-line therapy and personalized tumor neoantigen-loaded DC vaccine treatment plan will be designed for each participant. Here are the steps for preparing the neoantigen-loaded DC vaccine: Collecting venous blood samples; Blood PBMC exome sequencing; RNA transcriptome sequencing; Classifying HLA alleles; Performing bioinformatics analysis, finding meaningful mutations and about 20 neoantigen sequences for each patient; Synthesizing neoantigens; Use a blood apheresis device to collect the patient's blood, isolate the PBMC needed to prepare DC cells, and return the remaining blood components to the patient's body (approximately 10\^9 cells will be collected);Preparation of the personalized tumor neoantigen-loaded DC vaccine. Participants will receive a conventional third-line therapy course and 10 subcutaneous injections of the vaccine within a treatment period of 21 weeks. After treatment, participants will be followed in every 6 weeks till the end of the study. Venous blood collection, physical examination, ECOG Performance Status Scale assessment, CT/MRI scan, X-ray examination, laboratory examination, and other necessary examinations are required at each follow-up visit.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Conventional third-line therapy includes oral chemotherapy drugs and/or targeted cancer drugs. The medication, dosage and treatment cycle of oral chemotherapy drugs and/or targeted cancer drugs will be determined by the subject's attending physician based on the subject's specific circumstances.
The treatment with personalized tumor neoantigen-loaded DC vaccine is divided into two periods: the primary phase and the boost phase. The primary phase consists of 6 treatments, with the first 3 treatments spaced one week apart and the subsequent 3 treatments spaced two weeks apart. Vaccine will be administrated on the fourth day (D4) of that week. The boost phase consists of 4 treatments, each spaced three weeks apart. Vaccine will be administrated on the fourth day (D4) of that week.
First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, China
RECRUITINGThe First Hospital of Nanchang
Nanchang, Jiangxi, China
RECRUITINGObjective response rate (ORR)
According to RECIST (version 1.1) criteria, the proportion of subjects experiencing Complete Response (CR) or Partial Response (PR) within the analyzed population. Provide the 95% CI for the Objective Response Rate (ORR).
Time frame: Through study completion, an average of 32 weeks
Disease control rate (DCR)
According to RECIST (version 1.1) criteria, the proportion of subjects experiencing Complete Response (CR), Partial Response (PR), or Stable Disease (SD) within the analyzed population. Provide the 95% CI for the Disease Control Rate (DCR).
Time frame: Through study completion, an average of 32 weeks
Drug safety
Safety analysis will be based on data from the safety population. It will primarily involve descriptive statistical analysis, with tables describing the adverse events that occurred in this study.
Time frame: Through study completion, an average of 32 weeks
Progression-Free Survival (PFS)
Progression-Free Survival (PFS) is defined as the time from the first administration of the study drug to disease progression or death. For subjects who have not reported disease progression at the time of analysis, the date of their last disease progression-free check will be used as the censoring date. The median PFS and its 95% CI will be analyzed using the Kaplan-Meier method, and survival curves will be plotted.
Time frame: From date of recruiting until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 66 months
Overall Survival (OS)
Overall Survival (OS) is defined as the time from the first administration of the study drug to death from any cause. For subjects who have not reported death at the time of analysis, the date of their last known survival will be used as the censoring date. The median OS and its 95% CI will be analyzed using the Kaplan-Meier method, and survival curves will be plotted.
Time frame: From date of recruiting until the date of death from any cause, whichever came first, assessed up to 66 months
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