FMT in IT-refractory HCC - FAB-HCC Pilot Study

NCT05750030 | Completed Phase 2 DMC

• 2 other identifiers: FAB00012022-000234-42
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This single-center, pilot study (phase IIa) will evaluate the safety, feasibility, and efficacy of FMT from patients with HCC who responded to PD-(L)1-based immunotherapy to patients with HCC who failed to respond to atezolizumab/bevacizumab.

Conditions

Hepatocellular Carcinoma

Keywords

Fecal Microbiota Transplant; Hepatocellular Carcinoma; FMT; HCC; Immunotherapy; Atezolizumab; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• Safety of atezolizumab/bevacizumab in combination with FMT, 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.

  24 months

Secondary Outcomes (4)

• Efficacy assessed by the number of study participants achieving complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) as best radiological response evaluated according to mRECIST/ RECIST v1.1 criteria.

  24 months

• Efficacy as assessed by objective response rate (ORR) and disease control rate (DCR). Objective response is defined as either complete or partial response, while disease control rate comprises complete/partial response as well as stable disease.

  24 months

• Efficacy as assessed by progression-free survival (PFS) and overall survival (OS).

  24 months

• Quality of life (QoL) as assessed by the patient-reported outcome EQ-5D-5L (European Quality of Life 5 Dimensions 3 Level Version) questionnaire.

  24 months

Other Outcomes (5)

• Effect of FMT on recipient gut microbiota composition, diversity (alpha and beta), rate of change from baseline and similarity to donor stool composition over time as well as comparison of responders and non-responders.

  24 months

• Effect of FMT on immune activity in the gut by analyzing gut tissue samples with immunohistochemistry staining of immune cells of patients receiving FMT.

  24 months

• Differences in metagenome assemblies and functional profiling using shotgun metagenomic analysis of donor and recipient stool samples before and after FMT.

  24 months

Study Arms (1)

FMT combined with Atezolizumab plus Bevacizumab

EXPERIMENTAL

Combination Product: FMT combined with Atezolizumab plus Bevacizumab

Interventions

FMT combined with Atezolizumab plus Bevacizumab COMBINATION_PRODUCT

Single FMT from patients with HCC who responded to PD-(L)1-based immunotherapy to patients with HCC who failed to achieve complete or partial response (according to mRECIST) to atezolizumab/bevacizumab. After single FMT, patients will continue to receive atezolizumab/bevacizumab every 21-days according to protocol.

FMT combined with Atezolizumab plus Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form
• Age ≥ 18 years
• Histologically or radiologically confirmed HCC
• Patients with progressive disease (according to mRECIST) during treatment with atezolizumab/bevacizumab (without or with prior complete or partial response as best radiological response according to mRECIST) OR patients with stable disease as best radiological response (according to mRECIST) after the first 12 months of atezolizumab/bevacizumab treatment
• Negative HIV test
• Patients with chronic hepatitis B must be under antiviral treatment and hepatitis B DNA must be \< 500 IU/mL
• Variceal status must be known and if present, adequate medical or endoscopic treatment is required
• ECOG Performance Status 0-1
• Child-Pugh class A-B8
• Adequate hematological and end-organ function, defined as follows:
• AST and ALT \< 10 x ULN
• Serum bilirubin \< 3.5 mg/dL
• Albumin ≥ 28 g/L
• Serum creatinine ≤ 1.5 mg/dL
• Hemoglobin ≥ 8 mg/dL

You may not qualify if:

• Known fibrolamellar carcinoma or mixed cholangiocellular carcinoma
• Massive tumor progression (\> 100% increase in target lesions or progression associated with significant clinical deterioration)
• Uncontrolled ascites
• Overt hepatic encephalopathy or concomitant treatment with rifaximin
• Prior allogeneic stem cell or solid organ transplantation
• Active or history of severe autoimmune disease
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
• Pregnant or breastfeeding women
• Treatment with systemic immunosuppressive medication with the following exceptions:
• 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)
• Mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for adrenal insufficiency
• Serious, non-healing wound or active ulcer

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, 1090, Austria

Location

Related Publications (1)

• Pomej K, Frick A, Scheiner B, Balcar L, Pajancic L, Klotz A, Kreuter A, Lampichler K, Regnat K, Zinober K, Trauner M, Tamandl D, Gasche C, Pinter M. Study protocol: Fecal Microbiota Transplant combined with Atezolizumab/Bevacizumab in Patients with Hepatocellular Carcinoma who failed to achieve or maintain objective response to Atezolizumab/Bevacizumab - the FAB-HCC pilot study. PLoS One. 2025 Apr 15;20(4):e0321189. doi: 10.1371/journal.pone.0321189. eCollection 2025.

  PMID: 40233040 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Matthias Pinter, MD PhD

  Medical University of Vienna, Internal Medicine III, Department of Gastroenterology and Hepatology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical professor and principal investigator

Model Details: 12 Patients with HCC who failed to achieve or maintain a complete or partial response (according to mRECIST) to atezolizumab plus bevacizumab

Study Record Dates

• First Submitted: January 16, 2023
• First Posted: March 1, 2023
• Study Start: May 16, 2023
• Primary Completion: March 17, 2025
• Study Completion: March 17, 2025
• Last Updated: May 6, 2025

Record last verified: 2025-05

Locations

AU (1)