Patients With Hepatocellular Carcinoma (HCC)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Fecal microbiota transplantation performed via colonoscopy., Simulated Colonoscopy With Placebo Capsules in Addition to Standard Treatment.
- Who it may be relevant to
- Registry conditions: Hepatocellular Carcinoma, Hepatocellular Cancer, Liver Diseases, Liver Cancer. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Italy
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Fecal Microbiota Transplantation as a Response Booster in Patients With Hepatocellular Carcinoma Undergoing Immune Checkpoint Inhibitor Therapy
Overview
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.
Detailed description
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.
Finally, the study includes prospective collection of clinical outcomes, including disease progression, radiological response according to RECIST 1.1/mRECIST criteria, and survival. Treatment efficacy will primarily be assessed in terms of progression-free survival (PFS), complemented by secondary endpoints including objective response rate (ORR), disease control rate (DCR), time to progression (TTP), and overall survival (OS).
Interventions
- Procedure Fecal microbiota transplantation performed via colonoscopy.
Patients randomized to the intervention group will receive fecal microbiota transplantation (FMT) via colonoscopy. - Procedure Simulated Colonoscopy With Placebo Capsules in Addition to Standard Treatment
Patients assigned to the control group will undergo a simulated (sham) colonoscopy and will subsequently follow the same therapeutic regimen with placebo capsules, in addition to standard therapy.
Primary outcome measures
- Progression-Free Survival (PFS) [Time frame: 6-24 month]
Eligibility criteria
Inclusion criteria
- Age >18 years;
- Diagnosis of advanced or unresectable HCC;
- Patients undergoing standard therapy with immune checkpoint inhibitors (ICIs);
- Signed informed consent for study participation.
Exclusion criteria
- 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Double blind
- Primary purpose
- Treatment
Study locations
Italy · 1 center
- Fondazione Policlinico Universitaro A. Gemelli IRCSS,UOC Medicina Interna e Gastroenterolo — Roma
Identifiers
NCT: NCT07690683 · 27533