Clinical trial NCT06356597: Tislelizumab With Fruquintinib, Metronidazole, in Mismatch Repair-proficient or Microsatellite Stability, Advanced Colorectal Cancer: a Multicenter, Single Arm, Clinical Trial
Official title: Division of Gastroenterology and Hepatology,Renji Hospital, School of Medicine, Shanghai Jiao Tong University
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2024-04-10
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate the efficacy and safety of Tislelizumab with Fruquintinib, Metronidazole treatment in MSS/MSI-L advanced colorectal cancer patients with high abundance of Fusobacterium nucleatum in a single arm Phase II clinical.


Eligibility criteria: Inclusion Criteria:

1. No gender limit, age ≥ 18 years old and ≤ 80 years old;
2. Colorectal cancer (AJCC stage IV) diagnosed by histological or cytological biopsy as metastatic or unresectable, with immunohistochemical or genetic testing indicating MSS or MSH-L type;
3. Treatment requires third line or above, has previously received standard first and second line treatment, and the disease has progressed after treatment;
4. Before accepting tirelizumab, qPCR should be used to detect the Fn deltaCT value ≥ -22.24 in fecal samples;
5. ECOG score: 0-1 points;
6. Baseline blood routine and biochemical indicators meet the following criteria (no blood transfusion or use of colony stimulating factors 2 weeks prior to screening) Blood routine: hemoglobin ≥ 90g/L, absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet ≥ 100 × 109/L Liver function: ALT and AST ≤ 2.5 x ULN, serum total bilirubin ≤ 1.5 x ULN (if there is liver metastasis, ALT and AST ≤ 5 x ULN, serum total bilirubin ≤ 3 x ULN), serum albumin ≥ 30g/L Renal function: serum creatinine ≤ 1.5 x upper limit of normal (ULN), or creatinine clearance rate ≥ 50 mL/min (calculated according to Cockcroft Gault formula).
7. Those who voluntarily participate in the trial and sign an informed consent form.

Exclusion Criteria:

1. Pregnant or lactating women;
2. Chronic intestinal diseases (such as Crohn's disease, ulcerative colitis, etc.), infectious intestinal diseases during the screening period, and intestinal obstruction during the screening period;
3. Subjects with poor control of hypertension (systolic blood pressure\>150 mmHg and/or diastolic blood pressure\>100 mmHg) and a history of hypertensive crisis or hypertensive brain disease;
4. Severe liver and kidney function or heart dysfunction;
5. Patients who use antibiotics for more than 5 days within one month prior to immunotherapy;
6. Patients with known brain or meningeal metastases, regardless of whether they have received treatment, are not eligible for inclusion in this trial.
7. Individuals with contraindications to the use of metronidazole medication;
8. Those who are unwilling to participate in the trial or sign informed consent forms;
9. The researchers believe that there are any situations that are not suitable for selection.

Primary outcomes:
measure: objective response rate
timeFrame: 3 months and 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai First People's Hospital
city: Shanghai
country: China
facility: Shanghai Ninth People's Hospital
Study officials:
References:
citation: Jiang SS, Xie YL, Xiao XY, Kang ZR, Lin XL, Zhang L, Li CS, Qian Y, Xu PP, Leng XX, Wang LW, Tu SP, Zhong M, Zhao G, Chen JX, Wang Z, Liu Q, Hong J, Chen HY, Chen YX, Fang JY. Fusobacterium nucleatum-derived succinic acid induces tumor resistance to immunotherapy in colorectal cancer. Cell Host Microbe. 2023 May 10;31(5):781-797.e9. doi: 10.1016/j.chom.2023.04.010. Epub 2023 May 1.