Safety and Efficacy of Canagliflozin in Patients With Metastatic High Microsatellite Instability (MSI-H) Colorectal Cancer

Sponsor
West China Hospital
Study ID
NCT07076823
Phase
PHASE1
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Canagliflozin — DRUG
    Low-dose cohort: 100 mg qd, taken before the first meal of the day. High-dose cohort: Starting dose of 100 mg qd for 1 week. If tolerated, the dose will escalate to 300 mg qd, taken before the first meal of the day.

Study Details

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.

Key Dates

Start date
Jul 31, 2025
Status verified
Jul 2025
Primary completion
Jun 30, 2026
Completion
Jun 30, 2026

Study Design

Enrollment
15 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Intervention group
    PD-1 Inhibitor: Tislelizumab will be administered intravenously at the recommended dose of 200 mg every 3 weeks until disease progression or intolerable toxicity occurs. Canagliflozin: According to the drug's prescribing information, the recommended starting dose is 100 mg once daily (qd), taken orally before the first meal of the day. For patients who tolerate 100 mg qd and have an estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m² with a need for additional glycemic control, the dose may be increased to 300 mg qd. In this study's dose-escalation phase, two dose levels will be evaluated: Low-dose cohort: 100 mg qd, taken before the first meal of the day. High-dose cohort: Starting dose of 100 mg qd for 1 week. If tolerated, the dose will escalate to 300 mg qd, taken before the first meal of the day.

Primary Outcome Measure

Adverse Effect [ Time Frame: through study completion, an average of 1 year ]

Central Contacts

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