A Multicenter Clinical Study of Personalized Tumor Neoantigen-based Peptide Vaccine Combined with Conventional Third-line Therapy for the Treatment of Colorectal Cancer Progressed After Second-line Treatment
Overview
- Phase
- Not Applicable
- Intervention
- Neoantigen-based peptide vaccine
- Conditions
- Colorectal Cancer (CRC)
- Sponsor
- The First Affiliated Hospital of Nanchang University
- Enrollment
- 10
- Locations
- 2
- Primary Endpoint
- Objective response rate (ORR)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
In this study, the investigators provide a combined treatment of personalized tumor neoantigen-based peptide 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.
Detailed Description
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-based peptide vaccine treatment plan will be designed for each participant. Here are the steps for preparing the neoantigen-based peptide 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 peptide neoantigens; Preparation of the personalized tumor neoantigen-based peptide 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with histologically or cytologically confirmed CRC;
- •At least one measurable lesion;
- •Aged 18-70, regardless of gender;
- •Disease progression after standard second-line therapy, and more than 2 weeks since the end of the last antitumor treatment;
- •Expected survival of ≥3 months;
- •ECOG performance status of 0-1;
- •Female patients of childbearing age must have a negative pregnancy test and be able to take effective contraceptive measures with no plans for pregnancy within six months of the study;
- •Able to undergo all screening period laboratory tests as required by the protocol;
- •Normal major organ function, such as heart, liver, and kidney;
- •Hematologic parameters: neutrophil count ≥1.5×10\^9/L, hemoglobin ≥10g/dL, platelet count ≥100×10\^9/L, total bilirubin ≤1.5 times the upper limit of normal, AST and ALT ≤2.5 times the upper limit of normal, creatinine and blood urea nitrogen ≤1.5 times the upper limit of normal, activated partial thromboplastin time ≤1.5×ULN, and International Normalized Ratio or prothrombin time ≤1.5×ULN;
Exclusion Criteria
- •Disease-specific exclusion criteria:
- •Patients with uncontrollable brain metastases;
- •Subjects expected to require any form of antitumor treatment during the study, including maintenance therapy with other drugs, chemotherapy, and/or surgical resection.
- •Exclusion criteria for medical history and comorbidities:
- •Subjects who have required systemic treatment with corticosteroids (\>10 mg/day of prednisone or equivalent) or other immunosuppressants within 14 days before the first dose. Inhalational or topical corticosteroids are allowed in the absence of active autoimmune diseases;
- •Subjects who have been treated with anticancer immunotherapies or other immunostimulatory anticancer drugs (interferons, interleukins, thymosin, immune cell therapy, etc.) within 3 months before the first dose;
- •Subjects participating in other clinical trials or whose first dose is less than 4 weeks (or 5 half-lives of the study drug) after the end of the previous clinical trial (last dose);
- •Subjects with severe cardiovascular diseases, such as those meeting NYHA Class II or higher criteria, myocardial infarction, or cerebrovascular accidents (cerebral ischemia, symptomatic cerebral embolism, etc.) occurring within 3 months before the first dose, or unstable arrhythmias or unstable angina within 1 month before starting study treatment;
- •Subjects with uncontrolled myocardial ischemia or myocardial infarction, poorly controlled arrhythmias are excluded;
- •Subjects with hypertension that cannot be well controlled by antihypertensive medication (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg) (Note: a stable antihypertensive regimen should be in place within 1 week before the first dose);
Arms & Interventions
Combinational treatment of conventional third-line therapy and neoantigen-based peptide vaccine
Participants will receive a conventional third-line therapy and 10 subcutaneous injections of the vaccine within a treatment period of 21 weeks.
Intervention: Neoantigen-based peptide vaccine
Outcomes
Primary Outcomes
Objective response rate (ORR)
Time Frame: Through study completion, an average of 30 weeks
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).
Disease control rate (DCR)
Time Frame: Through study completion, an average of 30 weeks
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).
Drug safety
Time Frame: Through study completion, an average of 30 weeks
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.
Secondary Outcomes
- Progression-Free Survival (PFS)(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)(From date of recruiting until the date of death from any cause, whichever came first, assessed up to 66 months)