A Single-Center, Phase II, Randomized Controlled Clinical Study to Evaluate Dapagliflozin as an Addition to First-Line Treatment for Unresectable Hepatocellular Carcinoma With Metabolic Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 44
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
The goal of this interventional study (clinical trial) is to evaluate the efficacy and safety of adding dapagliflozin to first-line standard therapy in patients with unresectable hepatocellular carcinoma (HCC) and comorbid metabolic syndrome.
The main questions it aims to answer are:
Does the addition of dapagliflozin to first-line therapy improve the objective response rate (ORR) compared with first-line therapy alone in this patient population?
What are the differences between the two treatment groups in terms of overall survival (OS), progression-free survival (PFS), and safety/tolerability profiles?
Researchers will compare the combination group (dapagliflozin plus first-line standard therapy) with the control group (first-line standard therapy alone) to determine whether the addition of dapagliflozin provides superior clinical benefit.
Participants in the combination group will receive dapagliflozin in addition to their prescribed first-line standard therapy, while participants in the control group will receive first-line standard therapy alone. All participants will be regularly monitored for tumor response, survival outcomes, and adverse events throughout the study period.
The findings of this trial are expected to provide clinical evidence supporting the use of dapagliflozin as an adjunctive therapy in patients with advanced unresectable HCC and metabolic syndrome, potentially enhancing the tumor response rate to existing standard-of-care treatments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with hepatocellular carcinoma (HCC) at Barcelona Clinic Liver Cancer (BCLC) stage B (with large tumor burden exceeding the up-to-seven criteria) or stage C, as determined by consensus of a multidisciplinary hepatobiliary surgical team, corresponding to TNM stages II-IV with preserved liver function (intermediate to advanced HCC), who are deemed unresectable.
- •No prior systemic therapy for HCC.
- •First-line treatment regimen must include an immune checkpoint inhibitor with/without interventional therapy .
- •Diagnosis of metabolic syndrome according to the National Cholesterol Education Programme-Adult Treatment Panel III (NCEP-ATP III) criteria, requiring at least 3 of the following 5 criteria:
- •(1) Central obesity (waist circumference): ≥ 90 cm in males, ≥ 80 cm in females; (2) Elevated triglycerides: ≥ 150 mg/dL (1.7 mmol/L), or receiving specific treatment for this lipid abnormality; (3) Reduced high-density lipoprotein cholesterol (HDL-C): < 40 mg/dL (1.0 mmol/L) in males, < 50 mg/dL (1.3 mmol/L) in females, or receiving specific treatment for this lipid abnormality; (4) Elevated blood pressure: systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmHg, or previously diagnosed hypertension and receiving antihypertensive treatment; (5) Elevated fasting glucose: ≥ 100 mg/dL (5.6 mmol/L), or previously diagnosed type 2 diabetes mellitus.
- •5. Age between 18 and 75 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy > 3 months.
- •At least one measurable lesion according to RECIST version 1.1 (i.e., longest diameter ≥ 10 mm on contrast-enhanced spiral CT or contrast-enhanced MRI, or short-axis diameter ≥ 15 mm for enlarged lymph nodes; lesions previously treated with local therapy may be considered target lesions only if disease progression has been clearly documented per RECIST v1.1).
- •9. Adequate organ function, meeting the following laboratory criteria:
- •White blood cell count ≥ 4.0 × 10⁹/L
- •Neutrophil count ≥ 1.5 × 10⁹/L
- •Platelet count ≥ 80.0 × 10⁹/L
- •Hemoglobin ≥ 90 g/L
- •Serum albumin ≥ 2.8 g/dL
- •Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
- •ALT/AST/ALKP ≤ 2.5 × ULN
- •Serum creatinine ≤ 1.5 × ULN or creatinine clearance > 60 mL/min
- •No concomitant severe organic disease.
- •Ability to understand and willingness to provide written informed consent prior to any study-specific procedures, and agreement to comply with the study medication administration and post-treatment follow-up schedule as per protocol.
排除标准
- •Concomitant severe impairment of vital organ function (including cardiac, pulmonary, renal, or other major organ systems), active infections other than viral hepatitis, or other severe comorbid conditions that would render the patient unable to tolerate treatment.
- •Prior treatment with any sodium-glucose cotransporter 2 (SGLT2) inhibitor, including but not limited to canagliflozin, ertugliflozin, dapagliflozin, empagliflozin, luseogliflozin, and tofogliflozin.
- •Presence of contraindications to any component of the combination therapy, including immune checkpoint inhibitors, targeted therapy, or interventional therapy.
- •History of other active malignancies.
- •Concurrent autoimmune diseases, or other conditions requiring long-term systemic corticosteroid therapy.
- •Known or suspected hypersensitivity to the study drug or to any agent administered in association with this trial.
- •History of organ transplantation.
- •Pregnant or breastfeeding women.
- •Any other condition that, in the investigator's judgment, may interfere with patient enrollment or evaluation of study outcomes.
- •Refusal to comply with the follow-up requirements as specified in the protocol, or refusal to provide written informed consent.
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Three years
Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients.
次要结局
- Overall Survival (OS)(Three years)
- Progression-free Survival (PFS)(Three years)
- Adverse events (AE)(Three years)
研究者
Chen Min-Shan
Professor
Sun Yat-sen University