colorectal cancer
Conditions
Interventions
experimental group:HR0708035, FU/LV and BP102
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. 18-75 years of age and either sex; 2. Patients with pathologically confirmed advanced colorectal and rectal adenocarcinoma (all other histologic types excluded); 3. Previous failure of standard first-line therapy or disease progression during or =6 months after completion of adjuvant therapy; "Treatment failure" is defined as (1) disease progression during treatment or within 3 months of the last dose of treatment, with clear evidence of imaging or clinical progression, and (2) withdrawal from first-line treatment due to intolerance of an adverse event with an intolerable severity grade of an adverse hematologic event of grade IV or higher (platelet count decreased =1%), as defined by CTCAE 5.0 criteria. Grade IV or higher (platelet count decreased is Grade III or higher) or a non-hematologic adverse event severity grade of Grade III or higher, and in the judgment of the investigator, the subject would still be unable to tolerate treatment by repeating the original regimen. 4. The patient has at least one measurable target lesion according to RECIST 1.1 criteria; 5. ECOG score: 0~1 (see Annex II for details); 6. Expected survival =3 months; 7. Good function of major organs, i.e., relevant examination indexes meet the following requirements within 14 days before enrollment: (1) Routine blood tests (no blood transfusion within 14 days before screening, no drugs for raising white blood or platelets): hemoglobin > 90 g/L; neutrophil count > 1.5×109/L; platelet count > 100×109/L; (2) Biochemical tests: total bilirubin = 1.5×ULN (upper limit of normal); blood alanine aminotransferase (ALT) and blood azelaic transaminase (AST) = 2×ULN; if liver metastases are present, ALT and AST = 5×ULN; endogenous creatinine clearance = 60 ml/min (Cockcroft-Gault formula); (3) cardiac Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF, Left ventricular ejection fraction) = 50%. 8. The subject has recovered from the damage caused by other treatments; 9. Subjects voluntarily enrolled in the study, signed the informed consent form, had good compliance, and cooperated with the follow-up visits.
Exclusion criteria
Exclusion criteria: 1. Previous or concurrent other malignancies, except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix; 2. Patients who have received prior irinotecan therapy; 3. Tumor tissue with dMMR status confirmed by immunohistochemistry or MSI-H status by second-generation sequencing (NGS)/polymerase chain reaction (PCR). 4. BRAF V600E mutation confirmed by second-generation sequencing (NGS)/polymerase chain reaction (PCR); 5. Participation in a clinical trial of another drug within four weeks before enrollment; 6. presence of significant gastrointestinal abnormalities during the screening period that, in the judgment of the investigator, may interfere with the ingestion, transit, or absorption of the drug (e.g., inability to swallow, chronic diarrhea, intestinal obstruction, post-small bowel resection or total gastrectomy, etc.); or previous history of gastrointestinal perforation and/or fistulae; a history of peptic ulcer within 6 months before the first administration of the drug; and intestinal obstruction within 3 months before the first administration of the drug; 7. History of bleeding, any bleeding event with a severity rating of CTCAE 5.0 Grade 3 or higher within 4 weeks before screening; 8. Patients with known CNS metastases or a history of CNS metastases before screening. For patients with clinically suspected CNS metastases, an enhanced CT or enhanced magnetic resonance imaging (MRI) must be performed within 28 days before enrollment to rule out CNS metastases; 9. patients with hypertension that is not well controlled with a single antihypertensive medication (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg); those with a history of unstable angina; those with a new diagnosis of angina pectoris in the 3 months before screening or an incident myocardial infarction in the 6 months before screening; and those with cardiac arrhythmias (including QTcF: =450 ms for men and =470 ms for women) that require long-term Arrhythmia (including QTcF: =450 ms in men and =470 ms in women) requiring long-term use of antiarrhythmic drugs and New York Heart Association class =II cardiac insufficiency; 10. Urine protein =++ and confirmed 24-hour urine protein quantification >1.0 g; 11. long-standing unhealed wounds or incompletely healed fractures; 12. Imaging showing that the tumor has invaded the periphery of a vital blood vessel or if, in the judgment of the investigator, the patient's tumor has a very high likelihood of invading a vital blood vessel and causing fatal hemorrhage during treatment; 13. Abnormal coagulation function with a bleeding tendency (14 days before enrollment must be satisfied: INR within normal values without anticoagulants); patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin, or their analogs; and patients treated with an International Normalized Ratio of Prothrombin Time (INR ) = 1.5, low-dose warfarin (1 mg orally once daily) or low-dose aspirin (up to 100 mg daily) for prophylactic purposes are permitted; 14. Have had an arterial/venous thrombotic event within one year before screening, such as cerebrovascular accident (including temporary ischemic attack), deep vein thrombosis (except for venous thrombosis due to intravenous catheterization for pre-chemotherapy, which has resolved in the judgment of the investigator), and pulmonary embolism; 15. For female subjects: non-surgical sterilization or non-menopausal patients who refuse to use a m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| disease control rate;duration of remission;progression free survival;overall survival;quality of life; | — |
Countries
China
Contacts
Public ContactZhiyu Chen
Fudan University Shanghai Cancer Center
Outcome results
None listed