Colorectal cancer
Conditions
Interventions
Experimental group:Sintilimab combined with Fruquintinib and Fecal Microbiota Transplantation(FMT)
Sponsors
The First Affiliated Hospital with Nanjing Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: Voluntarily join the study and sign the informed consent; 1.Male or female, Age between 18 and 70; 2.Primary lesions with histologically-confirmed diagnosis of advanced colorectal cancer; 3.Non MSI-H/dMMR patients confirmed by immunohistochemistry and/or PCR; 4.Subjects who has relapsed after previous treatment of fluorouracil, oxaliplatin and irinotecan-based chemotherapy or combined with molecular targeted therapy or radiotherapy; 5.Subjects who never receive small-molecule antiangiogenic agents, like?fruquintinib, Regorafenib etc., and other other types of immune checkpoint inhibitors; 6.According to RECIST 1.1 criteria, subjects must have measurable lesions that can be evaluated by CT or MRI; Evaluation should be conducted within 28 days before first treatment; 7.Expected survival time>= 3 months; 8.ECOG-PS score 0-1; a.The function of heart, lung, liver and kidney should be normal, and the laboratory tests should meet the following requirements within 14 days: Hb>=100g/L; b.ANC>= 1.5×10^9/L; c.PLT>=100×10^9/L; d.ALB>=35g/L e.AST or ALT<= 1.5×ULN f.TBIL<= 30umol/L g.SCr<= ULN h.PT-INR<=2.3 or PT<6 seconds 10. Patients are expected to have good compliance and can follow up the efficacy and adverse reactions according to protocol requirements; 11.Asymptomatic brain metastases and no spinal cord compression; 12.Agree to provide blood samples for specific biomarker association studies; 13.Female subjects of childbearing age need to be negative for serum HCG and should be willing to use an effective method of contraception during treatment.
Exclusion criteria
Exclusion criteria: 1.Severely malnourished, or subjects requiring tube feeding; 2.Prior treatment with radiotherapy or surgery in the previous 30 days; 3.Prior treatment with anti-PD-1/L1 and mall-molecule antiangiogenic agents, like?Fruquintinib, Regorafenib etc.; 4.Subjects who have received antibiotics, probiotics or prebiotics-related products in the previous 14 days; 5.Serious infection (CTCAE > grade 2) within 4 weeks prior to first use of the study drug; 6.Suffered from other malignant tumors within 2 years before enrollment and uncured ;(Except for locally curable cancers (shown as cured), such as basal or skin squamous cell carcinoma and cervical carcinoma in situ; 7.Subjects with active autoimmune system diseases, or have suffered from autoimmune system diseases or symptoms according to course record, and need systemic hormone therapy or anti-autoimmune drug therapy; 8.Suffering from immunodeficiency, or still receiving systemic steroid hormone therapy (prednisone>10 mg/day or other equivalent drugs) 7 days before the first dose of treatment in this study, or other forms of immunosuppressive therapy patient; 9.Subjects with active infection who still need systemic treatment 7 days before the first dose of treatment in this study; 10.Subjects with uncontrollable systemic diabetes; 11.Subjects with interstitial lung disease, non-infectious pneumonia or pulmonary fibrosis; 12.Subjects who have ever received allogeneic organ or stem cell transplantation; 13.Subjects who are allergic to the drugs or related ingredients involved in this study; 14.Subjects who are currently participating in other interventional clinical studies; 15.The previous anti-tumor-related adverse reactions did not recover to CTCAE grade 1 before the first dose of treatment; 16.Subjects currently have hypertension that cannot be controlled by drugs, with SBP>= 140 mmHg and/or DBP >= 90 mmHg; 17.Subjects with thrombosis or bleeding tendency or medical history within 60 days before the first dose, regardless of severity; 18.Subjects with any serious or unstable medical condition or mental illness; patients with known active alcohol or drug abuse or dependenceeed for oral or intravenous antibiotic treatment, except in cases where prophylactic antibiotics are used
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| OS;PFS;DCR;QoL;Flow cytometry detection of IFN-?, CD8+ T cells, CD4+ T cells, Treg cells, related cytokines, etc. before and after treatment;TMB;Changes in gut flora; | — |
Countries
Not stated
Contacts
Public ContactGu Yanhong
The First Affiliated Hospital with Nanjing Medical University
Outcome results
None listed