Clinical trial NCT05690048: Fecal Microbiota Transfer in Liver Cancer to Overcome Resistance to Atezolizumab/Bevacizumab (FLORA)
Official title: Fecal Microbiota Transfer in Liver Cancer to Overcome Resistance to Atezolizumab/Bevacizumab (FLORA)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Immunotherapy
Keywords: immunotherapy
fecal microbiota transfer
HCC
gut microbiota
tumor microenvironment
Lead sponsor: University Hospital Heidelberg
Sponsor class: OTHER
Collaborators: name: National Center for Tumor Diseases, Heidelberg
name: German Cancer Research Center
name: Heidelberg University
name: University of Cologne
name: Universitätsmedizin Mannheim
First posted: 2023-01-19
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Interventional, randomized, controlled, single blind trial phase II with two arms (verum/placebo) in a parallel group design
Primary purpose: TREATMENT

Brief summary: The interventional, randomized, placebo-controlled, single blind phase II-trial FLORA will assess safety and immunogenicity of fecal microbiota transfer in combination with standard of care immunotherapy in advanced hepatocellular carcinoma (HCC) in a parallel group design.

Subjects will be randomized 2:1 into either the FMT or placebo group.

Detailed description: Eligible HCC patients visiting the outpatient clinics of LCCH at the study sites at NCT Heidelberg and University Medical Center Mannheim will be enrolled into the study after informed consent. Patients undergo 2:1 randomization into either the FMT or placebo group. Study lead in with a first sonographically guided tumor biopsy, if not already performed for diagnostic purposes, and a sigmoidoscopy will be scheduled within 10 days after study enrollment in an outpatient setting. Start of active pharmacotherapy with A/B will begin within five working days after sigmoidoscopy. A/B administration will be administered as standard of care every 21 days. At day -3 to 0 oral Vancomycin will be given 4x 250mg to the verum group. At day 0 and 21, concurrent to the first and second cycle of A/B, encapsulated FMT will be administered on the same day. At day 40-42, before the third cycle of A/B, a second biopsy of the liver lesion and a sigmoidoscopy will be performed. Clinical efficacy and safety will be assessed as indicated per protocol analysis.

Eligibility criteria: Inclusion Criteria:

1. Age 18 years or older
2. Confirmed imaging or histological diagnosis of unresectable HCC, BCLC stadium C
3. ECOG performance status of 0-1

Exclusion Criteria:

1. Advanced liver cirrhosis (Child-Pugh Score C)
2. Diagnosis of immunodeficiency (e.g. HIV, immunosuppressants)
3. Usage of antibiotics within 2 weeks prior enrollment

Primary outcomes:
measure: Differential tumoral CD8 T-cell infiltration
timeFrame: 6 weeks after treatment initiation
measure: Adverse event documentation of FMT in advanced HCC
timeFrame: Follow up 3 months after treatment initiation
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Follow up 3 months after treatment initiation
measure: Overall survival (OS)
timeFrame: Follow up 12 months after treatment initiation
measure: Change of Hepatic function
timeFrame: Follow up 3 months after treatment initiation
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
state: Baden-Württemberg
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
state: Baden-Württemberg
Study officials:
References: