Neoantigen-loaded DC Vaccine and Conventional Third-line Therapy for CRC Progressed After Second-line Treatment

NCT ID: NCT06751953

Last Updated: 2024-12-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-01
• Study Completion Date: 2027-02-28

Brief Summary

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.

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-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.

Conditions

Colorectal Cancer (CRC)

Keywords

Tumor Neoantigen; DC Vaccine; Colorectal Cancer (CRC); Immunotherapy; Third-line Therapy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combinational treatment of conventional third-line therapy and neoantigen-loaded DC vaccine

Participants will receive a conventional third-line therapy and 10 subcutaneous injections of the vaccine within a treatment period of 21 weeks.

Group Type: EXPERIMENTAL

Conventional third-line therapy

Intervention Type: COMBINATION_PRODUCT

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.

Neoantigen-loaded DC vaccine

Intervention Type: DRUG

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.

Interventions

Conventional third-line therapy

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.

Intervention Type: COMBINATION_PRODUCT

Neoantigen-loaded DC vaccine

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.

Intervention Type: DRUG

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;
• No active hepatitis, AIDS, syphilis, or other infectious diseases;
• Rheumatoid panel: C-reactive protein (CRP) ≤10.0mg/L; Anti-streptolysin O (ASO) <500U; Erythrocyte sedimentation rate ≤15mm/h (men) or 20mm/h (women);
• Thyroid function tests: 0.27mIU/L ≤ Thyroid-stimulating hormone (TSH) ≤ 4.2mIU/L; 3.1pmol/L ≤ Free triiodothyronine (FT3) ≤ 6.8pmol/L; 12pmol/L ≤ Serum free thyroxine (FT4) ≤ 22pmol/L; 1.3nmol/L ≤ Serum total triiodothyronine (TT3) ≤ 3.1nmol/L; 66nmol/L ≤ Serum total thyroxine (TT4) ≤ 181nmol/L;
• Adrenocorticotropic hormone (ACTH): 1.1-17.6pmol/L;
• Ability to understand and voluntarily sign a written informed consent form.

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.

• 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);
• Subjects who have had significant clinically relevant bleeding symptoms or a clear bleeding tendency within 3 months before the first dose, as well as tumors that have invaded major blood vessels or, in the investigator's judgment, are highly likely to invade major blood vessels and cause major bleeding during treatment. Subjects with obvious hemoptysis, coughing up 2.5 mL or more of blood in the month before the first dose;
• Subjects who have experienced arterial/venous thrombotic events, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral embolism), deep vein thrombosis, and pulmonary embolism, within 3 months before screening;
• Subjects with active tuberculosis;
• Subjects who have had a serious infection within 4 weeks before the first dose, including but not limited to infections requiring hospitalization, bacteremia, severe pneumonia, etc.; Subjects with any active infection;
• Subjects preparing for or who have previously undergone tissue/organ transplantation;
• Subjects with uncontrolled epilepsy, central nervous system disorders, or neurological diseases resulting in cognitive impairment;
• Subjects with a history of splenectomy.

• Pregnant or breastfeeding women;
• Subjects with a severe history of allergies or atopic constitution;
• Subjects with a history of chronic alcohol or drug abuse within 6 months before enrollment;
• Subjects deemed unsuitable for the study by the investigator.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Nanchang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status: RECRUITING

The First Hospital of Nanchang

Nanchang, Jiangxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yong Li, MD

Role: CONTACT

Phone: 15879155066

Email: Liyongcsco@email.ncu.edu.cn

Facility Contacts

Yong Li, MD

Role: primary

Jun Xu, MD

Role: primary

Other Identifiers

ISL2024313

Identifier Type: -

Identifier Source: org_study_id