MSS/pMMR metastatic colorectal cancer
Conditions
Interventions
Arm A: Irinotecan Liposome (II) + 5-FU/LV + Bevacizumab:Irinotecan Liposome (II) + 5-FU/LV + Bevacizumab
Arm B: Irinotecan Liposome (II) + 5-FU/LV + Bevacizumab + Camrelizumab:Irinotecan Liposome (II) + 5-FU/LV + Bevacizumab + Camrelizumab
Sponsors
Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18 to 75 years (inclusive, calculated from the date of signing the informed consent form), regardless of gender; 2. Patients with histopathologically and/or cytologically confirmed unresectable metastatic colon or rectal adenocarcinoma (Stage IV according to the UICC/AJCC TNM staging system); 3. Patients with microsatellite stable (MSS) or mismatch repair proficient (pMMR) status; 4. No prior systemic antitumor therapy for the current stage of disease (including but not limited to systemic chemotherapy, molecularly targeted therapy, immunotherapy, biotherapy, or other investigational treatments); if prior neoadjuvant or adjuvant therapy was received, the date of first disease recurrence/progression must be >= 6 months from the last dose of neoadjuvant or adjuvant therapy; 5. At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; the measurable lesion must not have received prior radiotherapy or other local therapy unless progression has occurred after such treatment (i.e., target lesions should not have received prior local therapy such as radiotherapy; however, lesions situated in a previously irradiated area may be selected as target lesions if progression is confirmed and they meet RECIST v1.1 criteria); 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 7. Life expectancy of >= 3 months; 8. Adequate organ function meeting the basic requirements for combination therapy, including generally normal peripheral blood counts, no significant abnormalities in cardiac, hepatic, or renal function, and generally normal electrocardiogram results. Specifically, organ function and relevant laboratory parameters within 14 days prior to initiation of study treatment must meet the following requirements (without the use of any blood components or hematopoietic growth factors during the screening period): Hematology: Absolute neutrophil count (ANC) >= 1.5 × 10^9/L; Platelet count (PLT) >= 100 × 10^9/L; Hemoglobin (Hb) >= 90 g/L; Blood Biochemistry: Serum albumin (ALB) >= 25 g/L; Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) = 60 mL/min (using the Cockcroft-Gault formula); Cardiac Function: Normal 12-lead electrocardiogram (ECG) or 12-lead ECG abnormalities deemed clinically insignificant by the investigator (i.e., QTcF = 50%; Coagulation: Prothrombin time (PT) or activated partial thromboplastin time (aPTT) <= 1.5 × ULN; International normalized ratio (INR) <= 1.5 × ULN (for patients not receiving anticoagulation therapy; for those on stable doses of anticoagulants such as low-molecular-weight heparin or warfarin with an INR within the expected therapeutic range, screening is permitted); 9. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose. Female patients of childbearing potential and their partners must agree to use adequate contraceptive methods during the trial and for 6 months after the completion of treatment; 10. Voluntary participation with signed informed consent, and ability to comply with the study visit schedule and other protocol requirements.
Exclusion criteria
Exclusion criteria: 1. Tumor- and Treatment-Related: (1) History of another malignancy within 5 years prior to screening, except for curatively treated basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, or other malignancies assessed by the investigator to have a low risk of metastasis and death; (2) Known tumor tissue status of mismatch repair deficient (dMMR) confirmed by immunohistochemistry, or microsatellite instability-high (MSI-H) confirmed by next-generation sequencing (NGS)/polymerase chain reaction (PCR), and assessed by the investigator as suitable for treatment with immune checkpoint inhibitors; (3) Confirmed BRAF V600E mutation by NGS/PCR, indicating a poor prognosis with chemotherapy; (4) Known central nervous system (CNS) metastases; for patients with clinically suspected CNS metastases, contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) must be performed within 28 days prior to initiation of study treatment to exclude CNS metastases; (5) Prior treatment with immune checkpoint inhibitors, including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies, or any cellular immunotherapy; (6) Prior treatment with irinotecan/irinotecan liposome-based chemotherapy; (7) Use of strong inhibitors or inducers of CYP3A4, CYP2C8, and UGT1A1 within 14 days prior to initiation of study treatment; (8) Participation in another clinical trial of a drug within 4 weeks prior to initiation of study treatment, except for observational (non-interventional) studies or follow-up periods of interventional studies; 2. Medical History or Comorbid Conditions: (1) Clinically documented severe gastrointestinal disorders (including bleeding, obstruction; inflammation > Grade 2 per NCI-CTCAE v5.0; diarrhea > Grade 1 per NCI-CTCAE v5.0), or other conditions judged by the investigator that might affect the ingestion, transit, or absorption of the study drug (including inability to swallow; status post small bowel resection or total gastrectomy); (2) Pleural effusion or ascites requiring clinical intervention (NCI-CTCAE v5.0 >= Grade 2); (3) Presence of severe comorbidities that would interfere with the study drug treatment: 1) Uncontrolled serious medical conditions judged by the investigator that would affect the subject's ability to receive the study regimen, such as severe concomitant internal diseases including severe heart disease, cerebrovascular disease, uncontrolled diabetes, uncontrolled hypertension, active peptic ulcer disease, etc.; 2) Occurrence of arterial/venous thrombotic events within one year prior to screening, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis (excluding venous thrombosis caused by venous catheterization for prior chemotherapy that has resolved as judged by the investigator), and pulmonary embolism; 3) Imaging evidence showing tumor invasion of major blood vessels, or patients judged by the investigator to have a very high risk of tumor invading major blood vessels during treatment, potentially leading to fatal massive hemorrhage; 4) History of interstitial lung disease or (non-infectious) pneumonitis requiring oral or intravenous corticosteroids; 5) Poorly controlled cardiac clinical symptoms or diseases, such as: New York Heart Association (NYHA) Class II or greater heart failure; unstable angina; myocardial infarction within the past 6 months; clinically significant supraventricula
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate, ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival, OS ;Disease control rate, DCR;Depth of Response (DpR);Safety;Progression Free Survival, PFS; | — |
Countries
China
Contacts
Public ContactGu Yanhong
Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University)
Outcome results
None listed