Advanced colorectal cancer
Conditions
Interventions
one:Efficacy and safety of nvolimab, lenvatinib mesylate combined with precision microbiota transplantation
Sponsors
Department of Oncology, Changzhi People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent before enrollment; subjects voluntarily joined the study, with good compliance, and cooperated with safety and survival follow-up. 2. Age >= 18 years old, both male and female; 3. Histologically or pathologically confirmed advanced colorectal cancer, pMMR or MSS; failure after at least two lines of therapy; 4. Detection of PD-L1 expression; detection of intestinal flora 16s rDNA; detection of recipe diversity with the participation of artificial intelligence. 5. Have measurable lesions (according to RECIST 1.1 criteria, the long diameter of CT scan of non-lymph node lesions is >= 10 mm, and the short diameter of CT scan of lymph node lesions is >= 15 mm); 6. ECOG score: 0-1; 7. The expected survival period is greater than 12 weeks; 8. The function of vital organs meets the following requirements (excluding any blood components and cell growth factors within 14 days): (1) Blood routine: Neutrophils>=1.5×10^9/L Platelet count>=100×10^9/L Hemoglobin >= 90g/L; (2) Liver and kidney function: Serum creatinine (SCr) = 2+, the 24-hour urine protein quantification shows that the protein must be less than or equal to 1g; 9. Normal coagulation function, no active bleeding and thrombotic disease (1) International standardized ratio INR<=1.5×ULN; (2) Partial thromboplastin time APTT<=1.5×ULN; (3) Prothrombin time PT<=1.5×ULN; 10. Non-surgical sterilization or female patients of childbearing age who need to use a medically approved contraceptive method (such as an intrauterine device, contraceptives or condoms) during the study treatment period and within 3 months after the end of the study treatment period; Female patients of reproductive age who are surgically sterilized must have a negative serum or urine HCG test within 7 days prior to study enrollment; and must be non-lactating; non-surgically sterilized or male patients of reproductive age, need to agree with their spouses during study treatment and research Use a medically approved form of birth control for 3 months after the end of the treatment period.
Exclusion criteria
Exclusion criteria: 1. The subject has suffered from other malignant tumors in the past 3 years or at the same time (except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix); 2. Those who have been treated with other PD-1/PD-L1 inhibitors in the past cannot be enrolled; the subjects are known to be allergic to macromolecular protein preparations, or known to be allergic to the applied drug components; 3. The subject has any active autoimmune disease or has a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis , nephritis, hyperthyroidism, hypothyroidism, those who have undergone thyroid surgery in the past cannot be included; subjects with vitiligo or complete remission of asthma in childhood, without any intervention in adulthood can be included; subjects need bronchial Asthma with medical intervention with dilators cannot be included); 4. Subjects are using immunosuppressive, or systemic, or absorbable topical hormone therapy to achieve the purpose of immunosuppression (dose > 10mg/day prednisone or other equivalent hormones), and within 2 weeks before enrollment is still in use; 5. Have used intravenous antibiotics, probiotics, and prebiotics within the past 4 weeks; 6. Clinical symptoms of ascites or pleural effusion require therapeutic puncture or drainage; 7. Have uncontrolled cardiac clinical symptoms or diseases, such as: (1) NYHA grade 2 or higher heart failure; (2) unstable angina pectoris; (3) myocardial infarction within 1 year; (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; 8. Subjects still using traditional Chinese medicine immunomodulators within 2 weeks before enrollment; 9. Subjects with active infection or unexplained fever > 38.5 degrees during the screening period and before the first administration (subject to the investigator's judgment, the subjects with fever due to tumor can be enrolled); 10. Patients with past and current objective evidence of history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severely impaired lung function, etc.; 11. Subjects with congenital or acquired immunodeficiency, such as HIV infection, or active hepatitis (hepatitis B reference: HBV DNA>=1000 IU/ml; hepatitis C reference: HCV RNA>=1000 IU/ml) ;Chronic hepatitis B virus carriers, HBV DNA <2000 IU/ml, must receive antiviral therapy at the same time during the trial to be enrolled; 12. Less than 4 weeks before the study medication or may be vaccinated with live vaccines during the study; 13. Subjects known to have a history of psychotropic substance abuse, alcoholism or drug use; 14. Subjects received traditional Chinese medicine treatment within 4 weeks before the first treatment; 15. The researcher believes that it should be excluded from this study. For example, according to the researchers judgment, the subject has other factors that may cause the study to be terminated halfway. For example, other serious diseases (including mental diseases) require combined treatment, There are serious laboratory abnormalities, accompanied by family or social factors, which will affect the safety of the subjects, or the collection of data and samples.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS);Progression Free Survival (PFS);16s rDNA diversity and abundance in gut microbiota;Gastrointestinal symptom score; | — |
Countries
China
Contacts
Public ContactJun Zhao
Changzhi People's Hospital
Outcome results
None listed