Neoantigen-based Peptide Vaccine and Conventional Second-line Therapy for CRC Progressed After First-line Treatment

NCT06751914 | Recruiting DMC

• 1 other identifier: ISL2024311
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

In this study, the investigators provide a combined treatment of personalized tumor neoantigen-based peptide vaccine and conventional second-line therapy to patients with colorectal cancer (CRC) progressed after first-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.

Conditions

Colorectal Cancer (CRC)

Keywords

Tumor Neoantigen; Peptide Vaccine; Colorectal Cancer (CRC); Immunotherapy; Second-line Therapy

Outcome Measures

Primary Outcomes (3)

• Objective 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).

  Through study completion, an average of 30 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).

  Through study completion, an average of 30 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.

  Through study completion, an average of 30 weeks

Secondary Outcomes (2)

• 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

Study Arms (1)

Combinational treatment of conventional second-line therapy and neoantigen-based peptide vaccine

EXPERIMENTAL

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

Combination Product: Conventional second-line therapy; Drug: Neoantigen-based peptide vaccine

Interventions

Conventional second-line therapy COMBINATION_PRODUCT

Conventional second-line therapy includes chemotherapy, targeted cancer drugs, and/or PD-1 inhibitors.The chemotherapy drugs, dosage and treatment cycle are determined by the subject's attending physician based on the subject's specific conditions. The medication, dosage and treatment cycle of targeted cancer drugs will be determined by the subject's attending physician based on the subject's specific circumstances. The PD-1 inhibitor treatment cycle is 3 weeks, and the drug is administered by intravenous infusion on the first day (D1) of each treatment cycle. The dosage is based on the instructions.

Combinational treatment of conventional second-line therapy and neoantigen-based peptide vaccine

Neoantigen-based peptide vaccine DRUG

The treatment with personalized tumor neoantigen-based peptide 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.

Combinational treatment of conventional second-line therapy and neoantigen-based peptide vaccine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically or cytologically confirmed CRC;
• At least one measurable lesion;
• Aged 18-70, regardless of gender;
• Disease progression after standard first-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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The First Affiliated Hospital of Nanchang University: lead

Study Sites (2)

First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

RECRUITING

The First Hospital of Nanchang

Nanchang, Jiangxi, 330006, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Yong Li, MD

CONTACT

15879155066; Liyongcsco@email.ncu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2024
• First Posted: December 30, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): February 28, 2027
• Last Updated: December 30, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)