Safety and Efficacy of Canagliflozin in Patients With Locally Advanced or Advanced Solid Cancer
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-80
SponsorWest China Hospital
About this trial
\*\*Revised version:\*\*
Locally advanced or advanced solid tumors remain a major clinical challenge despite multimodal treatments, including surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. For patients with unresectable, recurrent, metastatic, or treatment-refractory disease, prognosis remains poor, and effective therapeutic strategies are still urgently needed. Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 blockade, have transformed the treatment landscape of multiple solid tumors by reinvigorating anti-tumor immune responses through inhibition of the PD-1/PD-L1 pathway. However, only a subset of patients derive durable benefit from immunotherapy, and primary or acquired resistance remains common, highlighting the need for rational combination strategies to enhance anti-tumor efficacy.
Intriguingly, sodium-glucose cotransporter 2 inhibitors, originally developed as anti-diabetic agents, have shown emerging anti-tumor potential through metabolic regulation and modulation of the tumor microenvironment. In particular, combining SGLT-2 inhibition with immune checkpoint blockade may enhance tumor control through metabolic-immunologic crosstalk. Preclinical evidence suggests that the SGLT-2 inhibitor canagliflozin may suppress tumor growth and potentially improve the efficacy of PD-1 blockade. Based on this rationale, this phase I trial investigates the safety and efficacy of canagliflozin combined with tislelizumab in patients with locally advanced or advanced solid tumors, evaluating its impact on progression-free survival, overall survival, objective response rate, and tumor microenvironment modulation. This study aims to explore a novel metabolic-immunotherapy strategy based on dual metabolic and immune regulation, potentially providing a new therapeutic option for patients with locally advanced or advanced solid tumors.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Aged ≥18 years and ≤80 years old at the time of signing the written informed consent form, regardless of gender.
Patients with unresectable locally advanced, recurrent, or distant metastatic solid tumors.
Patients who have failed, are intolerant to, or are unsuitable for standard therapy, or for whom no standard therapy is available.
Patients considered suitable for treatment with tislelizumab-based immunotherapy by the investigator.
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
Canagliflozin
DrugLow-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.
Treatment groups
15 Participants
are divided into 1 treatment groupGroup A: Intervention groupExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Number of Participants With Treatment-Emergent Adverse Events as Assessed by CTCAE v5.0
Treatment-emergent adverse events will be assessed and summarized by number and percentage of participants, severity, seriousness, and relationship to study treatment.
Time frame
Through study completion, an average of 1 yearSecondary outcomes
1
Overall survival
Overall survival is defined as the time from the date of randomization to the date of death from any cause.
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 months2
Progression-Free Survival (PFS)
Progression-free survival is defined as the time from the date of randomization to the date of first documented disease progression or death from any cause, whichever occurs first.
Time frame
From date of randomization until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 100 months3
Immunogenicity assessment
Flow cytometry will be used to assess CD8+ T-cell function, proliferation, and polyfunctional T-cell subsets. Changes from baseline will be summarized descriptively.
Time frame
through study completion, an average of 1 year4
Gut Microbiome Metagenomic Profiling
Gut microbiome composition and functional profiles will be assessed using metagenomic sequencing of fecal samples. Exploratory analyses will include microbial diversity, relative abundance of key bacterial taxa, microbial functional pathways, and their association with treatment response, disease progression, and treatment-related adverse events.
Time frame
From baseline to treatment discontinuation, disease progression, death, or completion of study treatment, whichever occurs first.Other outcomes
1
Percentage of Prescribed Canagliflozin Doses Taken During Study Treatment
Medication adherence will be assessed as the proportion of prescribed canagliflozin doses actually taken during the treatment period. Adherence will be calculated based on drug accountability records, patient diaries, and/or returned tablets, and summarized as a percentage for each participant and overall.
Time frame
From initiation of canagliflozin treatment through treatment discontinuation or completion of study treatment, up to 1 year2
Change From Baseline in Blood Glucose Levels During Study Treatment
Blood glucose levels will be assessed during the study to evaluate metabolic changes associated with canagliflozin treatment. Changes from baseline in fasting blood glucose and/or random blood glucose will be summarized descriptively, and abnormal glucose-related events, including hypoglycemia or hyperglycemia, will be recorded when applicable.
Time frame
From baseline until treatment discontinuation, disease progression, death, withdrawal of consent, or completion of study treatment, whichever occurs first.3
Change From Baseline in Hemoglobin Levels During Study Treatment
Hemoglobin levels will be assessed during the study as part of hematologic safety monitoring. Changes from baseline in hemoglobin levels will be summarized descriptively, and clinically significant decreases in hemoglobin or anemia-related events will be recorded when applicable.
Time frame
Baseline and during study treatment, up to 1 yearSponsors and contacts
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Source ClinicalTrials.gov