Fecal Microbiota Transplantation as a Response Booster in Patients With Hepatocellular Carcinoma Undergoing Immune Checkpoint Inhibitor Therapy
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide and is frequently diagnosed at an advanced stage, resulting in limited therapeutic options. Despite the advances in immunotherapy, a substantial proportion of patients fail to respond adequately due to mechanisms of immune resistance. The gut microbiota plays a crucial role in modulating the response to immune checkpoint inhibitors (ICIs), and fecal microbiota transplantation (FMT) has demonstrated the ability to enhance their efficacy in other tumors, such as melanoma. In patients with HCC and cirrhosis, intestinal dysbiosis, characterized by a reduction in beneficial bacteria (e.g., Bifidobacterium, Akkermansia) and increased inflammation, is associated with an immunosuppressive profile. Furthermore, a dysbiosis index has been correlated with response to ICIs. In this context, FMT represents a promising strategy to enhance the efficacy of immunotherapy in HCC, although data regarding its efficacy and safety are still limited.
详细描述
The study includes an initial screening phase aimed at assessing patient eligibility and obtaining written informed consent. Subsequently, participants will undergo centralized randomization through dedicated software, according to a procedure designed to maintain blinding for both patients and clinical staff involved in the study, with the exception of the technical personnel responsible for the preparation of fecal microbiota transplantation (FMT).
Throughout the study, both procedures included in standard clinical practice and procedures specifically required by the study protocol will be performed. Routine clinical activities will include the collection of clinical, laboratory, and instrumental data already planned within the standard patient care pathway. Laboratory monitoring will be carried out every 2-3 weeks and will include complete blood count, liver and renal function tests, C-reactive protein, urinalysis, and alpha-fetoprotein measurement. Radiological follow-up will be performed by CT scan every three months.
Regarding study-specific procedures, patients assigned to the experimental arm will receive fecal microbiota transplantation according to procedures designed to ensure maintenance of study blinding. Scheduled follow-up visits will take place at baseline and subsequently at 1, 6, and 12 months.
In addition to blood samples already collected as part of routine clinical practice, an extra 10 mL blood sample and two fecal samples will be collected from each patient at the predefined study timepoints, namely at enrollment and at months 1, 6, and 12. The analysis of biological samples, with particular focus on gut microbiota characterization and bile acid profiling, represents an important scientific investigational tool. These analyses may contribute to a better understanding of systemic inflammatory status and the pathophysiology of the gut-liver axis, potentially providing clinically relevant information for a more comprehensive and personalized long-term management of the disease.
Biological samples and patient data will be collected exclusively after obtaining written informed consent and in full compliance with the approval of the competent Territorial Ethics Committee.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >18 years;
- •Diagnosis of advanced or unresectable HCC;
- •Patients undergoing standard therapy with immune checkpoint inhibitors (ICIs);
- •Signed informed consent for study participation.
排除标准
- •Presence of chronic intestinal diseases (e.g., inflammatory bowel disease, celiac disease);
- •Recent use of systemic antibiotics (within the previous 4-6 weeks);
- •Child-Pugh class > B8, ECOG performance status >1;
- •Any contraindication to colonoscopy.
研究组 & 干预措施
FMT arm
Fecal microbiota transplantation (FMT) will be administered by colonoscopy at the initiation of standard therapy, as part of routine clinical practice, followed by oral capsule administration in combination with standard treatment.
干预措施: Fecal microbiota transplantation performed via colonoscopy. (Procedure)
control arm
Patients assigned to the control arm will undergo a sham colonoscopy procedure, followed by administration of placebo capsules according to the same schedule, in combination with standard therapy.
干预措施: Simulated Colonoscopy With Placebo Capsules in Addition to Standard Treatment (Procedure)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: 6-24 month
Time from randomization to documented disease progression or death from any cause.
次要结局
未报告次要终点