metastatic colorectal cancer
Conditions
Interventions
safety run in:Irinotecan liposome + capecitabine + bevacizumab :safety run in. Irinotecan hydrochloride liposome injection (II) 80 mg/m2 (or 60mg/m2,if trigger dose down regulation)+ capecitabine 800
Efficacy expansion stage: Irinotecan liposome + capecitabine + bevacizumab :Efficacy expansion stage: Irinotecan hydrochloride liposome injection (II) RP2D+ capecitabine 800 mg/m+ bevacizumab 7.5 mg/k
Sponsors
Jiangsu Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age =18 years old and =75 years old, regardless of gender; 2. Diagnosis of colon or rectal cancer by histopathology and/or cytology with clinical records showing advanced metastatic colon or rectal cancer that is inoperable (i.e., stage IV according to the UICC/AJCC TNM staging system [8th edition 2017]); 3. According to the RECIST v1.1 standard, there should be at least one measurable target lesion (that is, the length of CT scan for non-lymph node lesions =10 mm, and the short diameter of CT scan for lymph node lesions =15 mm); 4. Previous first-line standard oxaliplatin ±VEGF/EGFR therapy for metastatic disease and treatment failure or intolerance *; * Definitions of treatment failure or intolerance: (1) disease progression during treatment or within 6 months after the last treatment, with clear imaging or clinical evidence of progression; (2) For patients who withdrew from first-line therapy due to an adverse event that they could not tolerate, intolerance was defined according to NCI-CTCAE v5.0 standards as: a. Hematological toxicity: Grade III neutropenia with fever > 38.5?, grade III thrombocytopenia with bleeding symptoms, other grade IV and above hematological toxicity; b. Non-hematological toxicity: Grade III and above non-hematological toxicity; c. If the above toxic reactions are achieved, the researchers judge that it is not suitable to continue the original treatment regimen. 5. Physical status score 0-1 of the Eastern Oncology Consortium (ECOG); 6. Expected survival time =3 months; 7. No major organ dysfunction, that is, the organ function level and related laboratory indicators of the subjects within 14 days before the start of the study and treatment must meet the following requirements: (1) blood routine (no blood transfusion, platelet transfusion, growth factor and other supportive treatment within 14 days before the start of the study and treatment) : white blood cell (WBC) =3.0×109/L; Absolute neutrophil count (ANC) =1.5×109/L; Platelet count (PLT) =100×109/L; Hemoglobin (Hb) =90 g/L (2) Blood biochemistry: serum albumin (ALB) = 30 g/L; Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =2.5 times the upper limit of normal (ULN), if there is liver metastasis ALT/AST=5×ULN; Total bilirubin (TBIL) =1.5×ULN; Serum creatinine (Cr) =1.5×ULN, or endogenous creatinine clearance =60 mL/min as calculated by Cockcroft-Gault formula (3) Urine routine: urine routine indicates urine protein <++; If urinary protein =++ at baseline, it is necessary to confirm that the 24-hour urinary protein quantity is =1.0g. (4) Coagulation function (within 14 days before the start of study treatment) : prothrombin time (PT) or activated partial thromboplastin time (aPTT) =1.5×ULN, International normalized ratio (INR) =1.5×ULN (did not receive anticoagulant therapy); Under test Patients should be treated with stable dose anticoagulants or vitamin K antagonists (such as warfarin, heparin, or their equivalents), and low doses of warfarin (1mg orally, 1mg orally, 1mg orally, 1mg orally, 1mg orally, and 1mg orally, are permitted for prophylactic purposes under the condition that the International Normalized ratio of prothrombin time (INR) is = 1.5. Once daily) or low-dose aspirin (up to 100 mg daily); (5) Cardiac function: normal 12-lead electrocardiogram or abnormal 12-lead electrocardiogram judged by the investigator to be clinically insignificant (i.e., QTcF < 450 ms in men and QTcF < 470 ms in women); Left ventri
Exclusion criteria
Exclusion criteria: 1.Have had malignancies other than colorectal cancer in the 5 years prior to screening (except cured basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and malignancies assessed by investigators as having a low risk of metastasis and death); 2. The tumor tissue is known to be in mismatch repair defect (dMMR) state confirmed by immunohistochemistry, or microsatellite high instability (MSI-H) state confirmed by second-generation sequencing (NGS)/polymerase chain reaction (PCR) method, It was evaluated by the researchers to be suitable for treatment with immune checkpoint inhibitors (PD-1/PD-L1 inhibitors) (Note: relevant reports could be submitted before enrollment; For subjects unable to provide a report, corresponding testing is recommended [optional]); 3. Second-generation sequencing (NGS)/polymerase chain reaction (PCR) method confirmed BRAF V600E mutation for patients with poor prognosis after chemotherapy (Note: relevant reports can be provided before entestation; For subjects unable to provide a report, corresponding testing is recommended [optional]); 4. For patients with known CNS metastases and clinically suspected CNS metastases, enhanced computed tomography (CT) or enhanced magnetic resonance imaging (MRI) must be performed within 28 days before the start of the study to rule out CNS metastases; 5. Previously received irinotecan/irinotecan liposome based chemotherapy; 6. Use of CYP3A4, CYP2C8, and UGT1A1 suppressors/inducers within 14 days prior to initiation of study therapy; 7. Participated in other drug clinical trials within 4 weeks before starting the study treatment; 8. Clinical records show severe gastrointestinal dysfunction (including bleeding, obstruction; NCI-CTCAE v5.0 > Grade 2 inflammation; Diarrhea (NCI-CTCAE v5.0 > 1), or other conditions (including inability to swallow) that the investigator determines may affect the ingestion, transport, or absorption of the drug; Small bowel resection or total gastrectomy, etc.); 9. Pleural effusion or ascites requiring clinical intervention (NCI-CTCAE v5.0=2); 10. The presence of serious comorbidities, active infections, or uncontrolled diabetes that impede treatment with the investigational drug: (1) A serious, uncontrolled medical condition that the investigator believes will affect the subject's ability to be treated with the study protocol, for example, complicated with serious internal disease, including severe heart disease, cerebrovascular disease, uncontrolled diabetes, uncontrolled hypertension, uncontrolled infection, active peptic ulcer, etc.; (2) Occurrence of arteriovenous thrombosis events within one year prior to screening, such as cerebrovascular accident (including temporary ischemic attack), deep vein thrombosis (except venous thrombosis caused by intravenous catheterization in previous chemotherapy and cured by investigators) and pulmonary embolism; (3) Imaging shows that the tumor has invaded the vicinity of important blood vessels or the investigator determines that the patient's tumor is highly likely to invade important blood vessels during treatment and cause fatal massive bleeding; (4) Prior interstitial lung disease, or (non-infectious) pneumonia requiring oral or intravenous steroid hormones; (5) have clinical symptoms or diseases of the heart that are not well controlled, such as: New York Heart Association (NYHA) level 2 or higher heart failure; Unstable angina pectoris; Myocardial infarction wi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| objective remission rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival;progression free survival;Disease control rate;security; | — |
Countries
China
Contacts
Public ContactLi Shen
Jiangsu Cancer Hospital
Outcome results
None listed