Patients with metastatic colorectal cancer who fail or do not tolerate first-line and second-line standard therapy
Conditions
Interventions
Experimental group:BC001 combined with TAS-102 treatment
Sponsors
Beijing University Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Subjects who meet all of the following criteria may be included in this study: 1. Participants should be able to understand and voluntarily sign written informed consent and to complete the study procedures and follow-up examinations. 2. Male or female subjects aged 18 years old. 3. Metastasis of histopathologically or cytopathologically proven chemotherapy based on fluorouracil, irinotecan, and prior incompatibility or intolerance to anti-vascular endothelial growth factor (VE GF) therapy, anti-epidermal growth factor receptor (EGFR) therapy (RAS wild-type) tumor progression or intolerance Patients with colorectal cancer, were determined to have at least one measurable tumor lesion demonstrated by CT or MRI according to version RECIST 1.1 *. * The measurable lesion is defined as a maximum diameter of 10mm with a scan thickness not exceeding 5.0mm. For lymph node lesions, the short diameter was 15mm. 4. The ECOG score is that of 0-1 points. 5. The expected survival period is greater than 3 months. 6. No serious haematological, hepatic and renal function abnormalities, meeting the following laboratory test results: 1) Hematology: neutrophils 1.510 9 / L, platelets 10010 9 / L, and hemoglobin 90g / L; 2) Liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 upper limit of normal (ULN) (or <5 ULN, if the liver is involved), total bilirubin <1.5 ULN (or <2 ULN if the liver and subjects with Gilbert disease); 3) Renal function: the creatinine clearance rate calculated according to the Cockcroft-Gault formula is 50 mL / min; 4) Coagulation function: international normalized ratio (INR) 1.5 or prothrombin time (PT) 1.5 ULN or activated partial prothrombin time (APTT) 1.5 ULN; 5) The urine protein results of routine urine test show 1 +. If the urine protein results of routine urine test show 2 +, the 24-hour urine protein quantification is <1g. 7. Recovery from baseline of adverse events of previous anti-tumor therapy or grade 1 (except: alopecia and vitiligo; stable or grade 2 neuropathy induced by previous anti-tumor therapy). 8 Male or female subjects will take effective contraception during treatment and within 6 months after the last dose.
Exclusion criteria
Exclusion criteria: Subjects who met any of the following criteria should be excluded from this study: 1. any previous systemic therapy targeting VEGFR2; previous TAS-102; systemic anti-tumor therapy (chemotherapy, targeted therapy, immunomodatory therapy, endocrine therapy, within 4 weeks or 5 known drug half-lives (subject to time older), including investigational or herbal drugs. 2. Failure to take oral medication, dysphagia, absorption disorder syndrome or any other impact on gastrointestinal drug absorption. 3. Patients with malignant disease other than the treated tumor of the study (exceptions include: cured and not recurrent within 3 years before study inclusion; completely removed basal and squamous cell skin carcinoma; completely removed of any type of carcinoma in situ). 4. Original lesion invasion and central nervous system (CNS) and symptomatic, unstable or requiring high-dose steroid (10mg dexamethasone or equivalent dose) to achieve control. 5. History of gastrointestinal perforation and / or fistula within 6 months prior to study medication; Grade 3 (CTCAE v 5.0) gastrointestinal bleeding within 3 months before study medication; inflammatory bowel disease or extensive bowel resection, Crohn's disease, ulcerative colitis, chronic diarrhea, or intestinal obstruction. 6 History of cirrhosis and hepatic encephalopathy of any degree, or clinically significant ascites caused by cirrhosis. 7 They had undergone major surgery within 4 weeks prior to study medication, or had undergone central venous catheterization within 7 days prior to enrollment. 8. Any life-threatening bleeding events occurred within the 3 months prior to the study medication, including blood transfusion therapy, surgical or topical treatment, and continuous drug therapy. 9. History of deep vein thrombosis, pulmonary embolism, or any other severe thromboembolism within the 3 months prior to study medication; receiving anticoagulation with farwarin, low-molecular-weight heparin, or similar formulation; patients receiving prophylactic low-dose anticoagulation may participate in the study with the anticoagulation parameters specified in the inclusion criteria (INR 1.5). 10 Is receiving long-term treatment with non-steroidal anti-inflammatory drugs (such as indopexacin, ibuprofen, etc.) or antiplatelet drugs (such as clopidogrel, ticlopidine, dipyridamole, etc.) (aspirin is permitted with a maximum daily dose of 325mg). 11. Live vaccine within 4 weeks before study medication; colony stimulating factor and erythropoietin within 2 weeks before study medication. 12 The subject had an uncontrolled interval disease, Including but not limited to: persistent or active infections requiring systemic antibiotic therapy (e. g., viral, bacterial or fungal infections); Symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease); Development of angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months prior to study medication; Stroke, transient ischemic attack (TIA), or other grade 3 arterial thromboembolic events within 6 months prior to study medication; Multidrug combination therapy for still uncontrolled hypertension (systolic 160mmHg and / or diastolic 100mmHg), presence of hypertensive crisis or hypertensive encephalopathy; Arrhythmias requiring treatment or an asymptomatic, persistent ventricular tachycardia; Grade 2 (CTCAE v 5.0) peripheral neuropathy of any etiology. 13. The presence of serious cardiovascular diseas
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| BC001 Safety of combined TAS-102 in patients with metastatic colorectal cancer who failed or tolerated first-line and second-line standard treatment, including: adverse events, blood routine, blood chemistry and urine routine, physical examination, vital signs and electrocardiogram results.; | — |
Secondary
| Measure | Time frame |
|---|---|
| BC001 Objective response rate (ORR), progression-free survival (PFS), duration of response (DOR), disease control rate (DCR), overall survival (OS), time to disease progression (TTP) and time to treatment failure (TTF) in patients with first-line metastatic colorectal cancer with TAS-102 and second-line standard therapy;BC001 Health-related quality of life assessment (HRQoL) in patients with TAS-102; | — |
Countries
CHINA
Contacts
Public Contactshenlin
Beijing University Cancer Hospital ?
Outcome results
None listed