Colorectal CancerPhase 1NCT07076823
Safety and Efficacy of Canagliflozin in Patients With Metastatic High Microsatellite Instability (MSI-H) Colorectal Cancer
A Phase 1 study testing Canagliflozin in people with Colorectal Cancer and SGLT-2 Inhibitor, run by West China Hospital at 1 site in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Colorectal Cancer, SGLT-2 Inhibitor
- What is being tested?
- Canagliflozin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteChina
- Study dates
- 31 Jul 2025to 30 Jun 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged ≥18 years and ≤80 years old at the time of signing the written informed consent form, regardless of gender.
- Patients with histologically or cytologically confirmed colorectal cancer, including:
- Patients with unresectable locally advanced, recurrent, or distant metastatic colorectal cancer.
- Patients with wild-type RAS/RAF and BRAF V600E genotypes in tumor tissues.
- Patients with microsatellite instability-high (MSI-H) colorectal cancer confirmed by MSI testing.
- Patients who have experienced disease progression after receiving at least two lines of standard treatment, or who cannot tolerate the toxic side effects.
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- According to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), patients must have at least one target lesion with measurable diameters (tumor lesions with a long diameter ≥10 mm on CT scan, lymph node lesions with a short diameter ≥10 mm on CT scan, and a scan slice thickness of no more than 5 mm). Lesions that have received local treatments such as radiotherapy can be used as target lesions after clear progression is confirmed.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1, with an expected survival period of ≥3 months.
- Patients must be type 2 diabetes mellitus (T2DM) patients and meet the indications for canagliflozin; or patients have no diagnosis of diabetes, no history of type 1 diabetes or diabetic ketoacidosis.
- The diagnosis of type 2 diabetes mellitus is defined as typical diabetic symptoms plus random blood glucose ≥11.1 mmol/L, or plus fasting blood glucose ≥7.0 mmol/L, or plus 2-hour post-load blood glucose in oral glucose tolerance test (OGTT) ≥11.1 mmol/L, or plus HbA1c ≥6.5%. For those without typical diabetic symptoms, reexamination on another day is required for confirmation (excluding random blood glucose).
- Good function of major organs, that is, the relevant examination indicators within 14 days before randomization meet the following requirements (without blood or blood product transfusion, without the use of hematopoietic stimulating factors, and without the use of albumin or blood products):
- Routine blood test: Hemoglobin ≥80 g/L; neutrophil count >1.5×10⁹/L; platelet count ≥90×10⁹/L.
- Biochemical test: Total bilirubin ≤1.5×ULN (upper limit of normal value); serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5×ULN; serum creatinine (SCr) ≤1.5×ULN or creatinine clearance rate ≥50 mL/min (Cockcroft-Gault formula).
- Prothrombin time (PT), international normalized ratio (INR) ≤1.5×ULN (unless warfarin anticoagulation is being used).
- Cardiac Doppler ultrasound evaluation: Left ventricular ejection fraction (LVEF) ≥50%.
- Renal function: eGFR ≥60 mL/min/1.73 m².
- Blood glucose: HbA1c ≤9%.
- Patients of childbearing potential (both male and female) must use effective medical contraceptive measures during the study period and within 6 months after the end of drug administration.
- Body mass index (BMI) ≥18.5 kg/m² during the study screening period.
- If complicated with hypertension, blood pressure must be controlled to a stable level with other medications.
- No history of peripheral vascular disease, neuropathy, or diabetic foot ulcers.
- Patients voluntarily join this study, sign the informed consent form, have good compliance, and patients and their families agree to cooperate with survival follow-up.
Who cannot join
- Participation in other drug clinical trials within 4 weeks.
- History of other tumors, except for in-situ cervical cancer, treated cutaneous squamous cell carcinoma, bladder epithelial tumors, or other malignant tumors that have received radical treatment (at least 5 years prior to enrollment).
- Patients with symptomatic or rapidly progressive central nervous system metastases, extensive lung metastases causing dyspnea, or tumors approaching or invading major blood vessels or nerves.
- Uncontrolled cardiac clinical symptoms or diseases, such as heart failure of NYHA class 2 or above, unstable angina, myocardial infarction within 1 year, or clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
- Pregnant or lactating women.
- Patients with active tuberculosis, bacterial or fungal infections (≥ grade 2, based on NCI-CTCAE 5.0), or HIV infection.
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- Patients with a history of psychoactive drug abuse that cannot be 戒除 (abstained from) or with mental disorders.
- Subjects with any active autoimmune diseases or a history of autoimmune diseases (including but not limited to: uveitis, enteritis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or childhood asthma that has fully remitted and requires no intervention in adulthood may be included; subjects with asthma requiring medical intervention with bronchodilators shall not be included).
- Previous treatment with SGLT2 inhibitors (such as dapagliflozin, empagliflozin, canagliflozin).
- Long-term steroid use or combined use of insulin/insulin sensitizers.
- Baseline HbA1c >10%, history of stroke or transient ischemic attack within 5 years, and uncontrolled comorbidities.
- Female subjects with a pregnancy plan or male subjects whose partners have a pregnancy plan from the screening period to 12 months after medication.
- CRC patients with known BRAF V600E mutation or peritoneal cancer patients.
- Patients with type 1 diabetes or diabetic ketoacidosis.
- History of peripheral vascular disease, neuropathy, or diabetic foot ulcers.
- Patients with severe renal insufficiency (eGFR <30 mL/min/1.73 m²).
- Patients with recurrent genitourinary infections within six months or requiring long-term anti-infective treatment.
- Patients with a history of lower limb amputation, severe peripheral vascular disease, or neuropathy.
- Patients with uncontrolled hypothyroidism.
- Other conditions deemed unsuitable for enrollment by the investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
West China Hospital
Chengdu, Sichuan, 610041
Nan Lin, +86 18708305692, sculinnan@qq.com
About this study
Official title: Safety and Efficacy of Canagliflozin in Patients With Metastatic High Microsatellite Instability (MSI-H) Colorectal Cancer: a Phase I Trial
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
- Colorectal Cancer, SGLT-2 Inhibitor
- Being tested
- Canagliflozin
- Keywords
- colorectal cancer, SGLT-2 inhibitor
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CanagliflozinDrug
Also called ICIs
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 group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | 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. Receives: Drug: Canagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Effect
Adverse Effect
Measured: through study completion, an average of 1 year
Secondary outcomes (2)
Overall survival
Overall survival
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Progression-Free Survival (PFS)
Progression-Free Survival (PFS)
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2025
- Study start31 Jul 2025 (estimated)
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by West China HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- West China Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xuelei Ma MD, West China Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07076823
- Sponsor's protocol ID
- Approval No. 729 (2025)
- Status last verified
- Jul 2025
- First submitted
- 23 Jun 2025
- Last updated
- 22 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Canagliflozin in Patients With Metastatic High Microsatellite Instability (MSI-H) Colorectal Cancer: a Phase I Trial
- ClinicalTrials.gov ID
- NCT07076823
- Acronym / sponsor ID
- Approval No. 729 (2025)
- Conditions
- Colorectal Cancer, SGLT-2 Inhibitor
- Keywords
- colorectal cancer, SGLT-2 inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- West China HospitalUniversity, hospital or other
- Study start
- 31 Jul 2025 (estimated)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 22 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Experimental | Drug: CanagliflozinPD-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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Aged ≥18 years and ≤80 years old at the time of signing the written informed consent form, regardless of gender.
- Patients with histologically or cytologically confirmed colorectal cancer, including:
- According to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), patients must have at least one target lesion with measurable diameters (tumor lesions with a long diameter ≥10 mm on CT scan, lymph node lesions with a short diameter ≥10 mm on CT scan, and a scan slice thickness of no more than 5 mm). Lesions that have received local treatments such as radiotherapy can be used as target lesions after clear progression is confirmed.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1, with an expected survival period of ≥3 months.
- Patients must be type 2 diabetes mellitus (T2DM) patients and meet the indications for canagliflozin; or patients have no diagnosis of diabetes, no history of type 1 diabetes or diabetic ketoacidosis.
Key exclusion criteria (20 listed)
- Participation in other drug clinical trials within 4 weeks.
- History of other tumors, except for in-situ cervical cancer, treated cutaneous squamous cell carcinoma, bladder epithelial tumors, or other malignant tumors that have received radical treatment (at least 5 years prior to enrollment).
- Patients with symptomatic or rapidly progressive central nervous system metastases, extensive lung metastases causing dyspnea, or tumors approaching or invading major blood vessels or nerves.
- Uncontrolled cardiac clinical symptoms or diseases, such as heart failure of NYHA class 2 or above, unstable angina, myocardial infarction within 1 year, or clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
- Pregnant or lactating women.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CanagliflozinAlso: ICIsLow-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. | Drug | Intervention group |
Primary outcome
Adverse Effect
Time frame: through study completion, an average of 1 year
Adverse Effect
2 secondary outcomes
Overall survival
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Progression-Free Survival (PFS)
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2025.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Canagliflozin in people with Colorectal Cancer and SGLT-2 Inhibitor, run by West China Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nan Lin, MD (+86 18708305692, sculinnan@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Effect (time frame: through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2025.