Colorectal cancer
Conditions
Interventions
TAS-102+Fruquintinib+Sintilimab:Cohort A: TAS-102 25mg/m2, bid,oral dosing,d1-d5+Fruquintinib 3 mg QD, oral dosing, d1-14 + Sintilimab 200mg Q3W, intravenous dosing.
Cohort B: TAS-102 30mg/m2, bid,or
TAS-102+Fruquintinib+Sintilimab:According to phase I results, PR2D TAS-102 dose was 25 to 35mg/m2 orally, d1-d5, q3w+ Fruquintinib 3 mg QD, oral dosing, d1-14,Q3W+Sintilimab 200mg Q3W, intravenous dos
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have fully understood and voluntarily sign the ICF for this study (the ICF must be signed before any trial-specific procedures are performed); Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure; 2. Histologically and/or cytologically documented metastatic colorectal adenocarcinoma; 3. Microsatellite stable (MSS) or microsatellite instability-low (MSI-L) or DNA mismatch repair gene expression is normal(pMMR); 4. Recurrent or metastatic disease; 5. Patients who have previously failed systemic therapy for recurrent or metastatic colorectal cancer, or who are intolerant to treatment, disease progression must not exceed 3 months after the last systemic therapy. Systemic therapy must contain fluorouracil, oxaliplatin, and irinotecan, with or without targeted therapy (bevacizumab,cetuximab, etc.); 6. With one or more measurable lesions, the longest diameter should be at least 10 mm measured by Magnetic resonance imaging (MRI) or Computed tomography (CT) scan, or at least 20 mm by conventional CT scan should be(RECIST standard, version 1.1); 7. ECOG performance status (ECOG PS) of 0 or 1; 8. Life expectancy of at least 3 months; 9. No serious organic diseases of heart, lung, brain and other organs; 10. The main organs and bone marrow function normally: a).WBC >= 4.0 x 10^9 /L; Absolute neutrophil count (ANC) >= 1.5×10^9/L; platelets >= 85×10^9/L;hemoglobin >= 90 g/L; b).International normalized ratio (INR) = 29g/L; d).Serum creatinine = 50mL/min; e) Protein urine = 2+, 24-hour protein urine quantification should be = 60%; 13. For female participants of childbearing potential and male participants with partners of childbearing potential, agreement to use a highly effective form(s) of contraception, that results in a low failure rate (<1% per year) when used consistently and correctly, starting during the screening period, continuing throughout the entire study period, and for 90 days after taking the last dose of study drug. Such methods include:oral hormonal contraception (combined estrogen/ progestogen, or progestogen-only) associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal ligation, vasectomized partner, or true sexual abstinence in line with the preferred and usual lifestyle of the participant. Highly effective contraception should always be combined with an additional barrier method (eg, diaphragm, with spermicide). The same criteria are applicable to male participants involved in this clinical trial if they have a partner of childbirth potential, and male participants must always use a
Exclusion criteria
Exclusion criteria: 1. Participated in other anti-tumor drug clinical trials within 4 weeks before enrollment; 2. Patients With known high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR); 3. Previously received anti-programmed death-1 (PD-1) or its ligand(PD-L1) antibody or PD-L2 antibody , anti-cytotoxic T lymphocyteassociated antigen 4 (cytotoxic T-lymphocyte-associated Protein 4,CTLA-4) antibody or other drug/antibody that acts on T cell costimulation or checkpoint pathways; 4. Have had other malignancies within the past 5 years, except for curatively treated radical skin basal cell or squamous cell carcinoma, or cervical carcinoma in situ; 5. Patients who have had or are currently having any brain metastases; 6. Any surgery or invasive treatment within 4 weeks before the first dose(stable fistula formation required for fistulization for 4 weeks, except needle biopsy, venous fistula); or unhealed wounds, ulcers, fractures; 7. Local anti-tumor therapy such as hepatic artery interventional embolization, liver metastasis cryoablation or radiofrequency ablation was performed within 4 weeks before enrollment. 8. The investigators identified clinically significant electrolyte abnormalities; 9. Patients with hypertension uncontrolled by drugs, defined as: systolic blood pressure >= 140 mmHg and/or diastolic blood pressure >= 90 mmHg; 10. Urine routine indicated urinary protein >= 2+, and 24-hour urinary protein quantity >1.0g; 11. The researchers determined that during the follow-up study, the tumor was at high risk of invading important blood vessels and causing fatal bleeding; 12. Obvious clinical bleeding symptoms or obvious bleeding tendency within 3 months prior to treatment (bleeding > 30 mL within 3 months,hematemesis, black stool, blood in the stool), hemoptysis (> 5 mL of fresh blood within 4 weeks), etc.Patients with a history of inherited or acquired bleeding or coagulation disorders.Have clinically significant bleeding symptoms or definite bleeding tendency within 3 months, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, etc.; 13. Abnormal coagulation function (INR > 2.0, PT > 16s), bleeding tendency or severe thrombotic disease require long-term oral anticoagulant or antiplate therapy; 14. Patients with clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina or coronary artery bypass grafting within 6 months before the first dose; congestive heart failure of New York Heart Association (NYHA) class > 2; Electrocardiogram (ECG) showed QT c 30 interval >= 480 msec; 15. Active or uncontrolled severe infection (>= CTCAE grade 2 infection); 16. Unmitigated toxicity higher than CTCAE grade 2 due to any previous anticancer therapy, excluding alopecia, lymphocytopenia, and oxaliplatin grade =2 neurotoxicity; 17. Pregnant or lactating female subjects; 18. Any other medical condition, clinically significant metabolic abnormality,physical abnormality or laboratory abnormality, in which, in the investigator's judgment, there is reason to suspect that the patient has a medical condition or condition that is not suitable for the use of the investigational drug (such as having seizures and requiring treatment),or which would affect the interpretation of the study results or place the patient at high risk; 19. Known human immunodeficiency virus (HIV) infection; Known history of clinically significant liver disease, including viral hepatitis [active HBV infe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose Limited Toxicity (DLT);Maximum Tolerated Dose (MTD);Recommended Phase II Dose;Objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| incidence, severity and outcomes of AEs (Adverse Event);Disease control rate;Duration of Response (DOR);Progression Free Survival (PFS);Overall survival;Time to progression (TTP); | — |
Countries
China
Contacts
Public ContactDongsheng Zhang
Sun Yat-sen University Cancer Center
Outcome results
None listed