Actively Recruiting
Safety and Efficacy of Canagliflozin in Patients With Metastatic High Microsatellite Instability (MSI-H) Colorectal Cancer
Led by West China Hospital · Updated on 2025-07-22
15
Participants Needed
1
Research Sites
47 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Colorectal cancer (CRC), ranking third in incidence among men and second in women globally with third-highest mortality in the US, remains a major health challenge despite multimodal therapies, particularly for advanced-stage patients with poor prognosis where immune checkpoint inhibitors (ICIs) like PD-1/PD-L1 blockers have emerged as transformative agents by reinvigorating anti-tumor immunity through PD-1/PD-L1 pathway inhibition. While MSI-H CRC's high mutational burden renders it susceptible to immunotherapy, clinical trials demonstrate durable responses with domestic ICIs such as tislelizumab showing 41.2% ORR, 14.4-month PFS, and 28.7-month OS in metastatic MSI-H CRC, yet unmet needs persist. Intriguingly, SGLT-2 inhibitor exhibit promising oncolytic potential, particularly when combined with ICIs, as evidenced by observational studies revealing enhanced tumor control in pancreatic ductal adenocarcinoma through metabolic-immunologic crosstalk and our preclinical data showing synergistic CRC growth suppression with the SGLT-2 inhibitor canagliflozin plus PD-1 blockade. This phase II trial investigates the safety and efficacy of canagliflozin-tislelizumab combination in metastatic MSI-H CRC, evaluating its impact on PFS, OS, and ORR while dissecting tumor microenvironment modulation mechanisms, thereby pioneering a novel metabolic-immunotherapy paradigm that could redefine treatment paradigms through dual metabolic-immune regulation.
CONDITIONS
Official Title
Safety and Efficacy of Canagliflozin in Patients With Metastatic High Microsatellite Instability (MSI-H) Colorectal Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Aged 18 to 80 years at the time of informed consent, any gender
- Histologically or cytologically confirmed colorectal cancer
- Unresectable locally advanced, recurrent, or distant metastatic colorectal cancer
- Wild-type RAS/RAF and BRAF V600E genotypes in tumor tissues
- Microsatellite instability-high (MSI-H) colorectal cancer confirmed by MSI testing
- Disease progression after at least two lines of standard treatment or intolerance to toxic side effects
- At least one measurable target lesion according to RECIST 1.1 criteria
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, with expected survival of at least 3 months
- Type 2 diabetes mellitus patients who meet indications for canagliflozin, or patients without diabetes, type 1 diabetes, or diabetic ketoacidosis
- Good major organ function with specified laboratory values within 14 days before randomization
- Use of effective contraception for patients of childbearing potential during the study and for 6 months after
- Body mass index (BMI) of at least 18.5 kg/m2 during screening
- Controlled blood pressure if hypertensive
- No history of peripheral vascular disease, neuropathy, or diabetic foot ulcers
- Voluntary participation with signed informed consent and agreement to follow-up
You will not qualify if you...
- Participation in other drug clinical trials within 4 weeks
- History of other tumors except treated in-situ cervical cancer, cutaneous squamous cell carcinoma, bladder epithelial tumors, or other malignancies treated with radical intent over 5 years ago
- Symptomatic or rapidly progressive central nervous system metastases, extensive lung metastases causing breathing difficulty, or tumors invading major blood vessels or nerves
- Uncontrolled cardiac conditions including heart failure NYHA class 2 or above, unstable angina, recent myocardial infarction, or serious arrhythmias needing treatment
- Pregnant or breastfeeding women
- Active tuberculosis, bacterial or fungal infections grade 2 or higher, or HIV infection
- History of psychoactive drug abuse or mental disorders
- Active or history of autoimmune diseases except certain fully remitted conditions
- Previous treatment with SGLT2 inhibitors
- Long-term steroid use or combined insulin/insulin sensitizer therapy
- Baseline HbA1c above 10%, recent stroke or transient ischemic attack, or uncontrolled comorbidities
- Pregnancy plans during study and 12 months after medication
- CRC patients with known BRAF V600E mutation or peritoneal cancer
- Type 1 diabetes or diabetic ketoacidosis
- History of peripheral vascular disease, neuropathy, or diabetic foot ulcers
- Severe renal insufficiency (eGFR below 30 mL/min/1.73 m2)
- Recurrent genitourinary infections or need for long-term anti-infective treatment
- History of lower limb amputation or severe peripheral vascular disease
- Uncontrolled hypothyroidism
- Other conditions making enrollment unsuitable per investigator judgment
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
West China Hospital
Chengdu, Sichuan, China, 610041
Actively Recruiting
Research Team
N
Nan Lin, MD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here