Role of Fecal microbiota transplantation in treatment-naïve advanced hepatocellular carcinoma: a double-blind placebo-controlled pilot randomised controlled trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Efficacy of FMT in combination with systemic therapy, assessed by the number of study participants achieving complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) as best overall response evaluated according to mRECIST criteria
研究概览
简要总结
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for approximately 75-85% of cases worldwide. A substantial proportion of patients don’t show response with around 25-50% patients having disease progression on existing first-line treatment modalities (immunotherapy and targeted therapies) in unresectable hepatocellular carcinoma. Fecal microbiota transplantation (FMT) is a process of transferring stool samples collected from a healthy donor to the patient’s intestine. Fecal microbiota transplantation has been shown to be safe and effective in other malignancies like malignant melanoma. It plays a complementary role in modulating tumor microenvironment and increases response rates to immunotherapy in these patients. Therefore, we plan to explore the role of fecal microbiota transplantation in increasing the efficacy of existing therapies in unresectable hepatocellular carcinoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Age more than or equal to 18 years
- •Radiologically or histologically confirmed Hepatocellular carcinoma
- •Barcelona Clinic Liver Cancer stage C
- •ECOG performance status 0-2
- •Child pugh class A5-B8
- •Adequate hematological and end-organ function, defined as follows: a.
- •AST and ALT less than 5 x ULN b.
- •Serum bilirubin less than 3 mg/dL c.
- •Serum creatinine less than or equal to 1.5 mg/dL d.
- •Hemoglobin more than or equal to 8 mg/dL e.
- •Platelet count more than or equal to 50k f.
- •Written informed consent.
排除标准
- •Known fibrolamellar carcinoma or mixed cholangiocellular carcinoma B.
- •Concomitant other malignancies C.
- •Uncontrolled ascites D.
- •Overt hepatic encephalopathy or concomitant treatment with rifaximin E.
- •Not able to undergo UGI endoscopy F.
- •Prior locoregional therapy G.
- •Prior allogeneic stem cell or solid organ transplantation H.
- •Recent antibiotic use within 2 months I.
- •Prior history of fecal microbiota transplantation J.
- •Active or history of severe autoimmune disease K.
- •Severe infection within 4 weeks prior to study inclusion L.
- •Active infection at the time of enrollment M.
- •Pregnant or breastfeeding women N.
- •Treatment with systemic immunosuppressive medication with the following exceptions: a.
- •Acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for contrast allergy) b.
- •Mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for adrenal insufficiency O.
- •Major surgery within 4 weeks prior to study inclusion or minor surgery (excluding placement of a vascular access device) within 3 days prior to study inclusion P.
- •History of gastrointestinal fistula or perforation, or intra-abdominal abscess within 6 months prior to study inclusion Q.
- •Serious, non-healing wound or active ulcer R.
- •Any clinical or laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications.
结局指标
主要结局
Efficacy of FMT in combination with systemic therapy, assessed by the number of study participants achieving complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) as best overall response evaluated according to mRECIST criteria
时间窗: 6 months
次要结局
- Efficacy of FMT in combination with systemic therapy, assessed by objective response rate (ORR) and disease control rate (DCR)(6 months)
- Efficacy of FMT in combination with systemic therapy, assessed by progression-free survival (PFS) and overall survival (OS).(24 months)
- Safety of FMT in combination with systemic therapy, measured by incidence and severity of treatment-related adverse events, determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.5.0(6 months)
- Effect of FMT on recipient gut microbiota composition and diversity (alpha and beta), rate of change from baseline and similarity to donor stool composition over time(2 months)
- Differences in circulating immune cells and microbial metabolites in patients before and after FMT.(2 months)
- Quality of life as reported by EORTC QLQ-C30 and QLQ-HCC18(6 months)
研究者
Dr Shalimar
All India Institute of Medical Sciences, New Delhi