Fecal Microbiota Transfer in Liver Cancer to Overcome Resistance to Atezolizumab/Bevacizumab (FLORA)

Immunotherapy Clinical Trial

— FLORA  

Official title:

Fecal Microbiota Transfer in Liver Cancer to Overcome Resistance to Atezolizumab/Bevacizumab (FLORA)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05690048
• Other study ID #: Version 1.0/07.12.2022
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 1, 2024
• Est. completion date: March 1, 2027

Study information

• Verified date: January 2023
• Source: University Hospital Heidelberg
• Contact: Michael T Dill, PhD
• Phone: 06221 568611
• Email: michael.dill[@]med.uni-heidelberg.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 48
• Est. completion date: March 1, 2027
• Est. primary completion date: July 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Immunotherapy
• Liver Neoplasms

Intervention

Drug:
• Fecal microbiota transfer
FMT via capsule (50 g of fecal matter) on day 0 and day 21.
• Vancomycin Oral Capsule
Vancomycin orally (125 mg 4xd, day -3 to 0).
• Atezolizumab + Bevacizumab
Atezolizumab 1200mg i.v. & Bevacizumab 15mg/kg body weight i.v. (A/B) as standard of care (SOC).
• Placebo Vancomycin Oral Capsule
Placebo Vancomycin orally (125 mg 4xd, day -3 to 0).
• Placebo Fecal microbiota transfer
Placebo Fecal microbiota transfer (FMT) via capsule (50 g of fecal matter) on day 0 and day 21.

Locations

Country	Name	City	State
Germany	University Hospital Heidelberg	Heidelberg	Baden-Württemberg
Germany	University Hospital Heidelberg	Heidelberg	Baden-Württemberg

Sponsors (6)

Lead Sponsor	Collaborator
Michael Dill	German Cancer Research Center, Heidelberg University, National Center for Tumor Diseases, Heidelberg, Universitätsmedizin Mannheim, University of Cologne

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differential tumoral CD8 T-cell infiltration	Tumoral CD8 T-cells in IHC before treatment initiation and 6 weeks after (CD8-cells/area of tumor tissue in formalin embedded tumor tissue)	6 weeks after treatment initiation
Primary	Adverse event documentation of FMT in advanced HCC	Adverse event documentation [AE] & immune-related adverse events [irAE])	Follow up 3 months after treatment initiation
Secondary	Progression-free survival (PFS)	Progression-free survival as by RECIST1.1 criteria	Follow up 3 months after treatment initiation
Secondary	Overall survival (OS)	Overall survival	Follow up 12 months after treatment initiation
Secondary	Change of Hepatic function	Assessment of Model of End-Stage Liver Disease Score in blood (MELD-Score, 6-40, higher score refers to worse hepatic function)	Follow up 3 months after treatment initiation