Home › Trials › NCT05690048
Clinical trial Recruiting at 1 site Phase 2 Interventional Ages 18 and up

Fecal microbiota transfer to overcome resistance to atezolizumab/bevacizumab in liver cancer

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

Run by University Hospital Heidelberg · NCT05690048 · Data updated 2026-11-12

This will test whether adding fecal microbiota transfer to standard atezolizumab/bevacizumab helps adults with advanced hepatocellular carcinoma respond better.

More Immunotherapy trials

Quick facts

PhasePhase 2
Study typeInterventional
Ages18 Years and up
SexAll
Enrollment48 (estimated)
SponsorUniversity Hospital Heidelberg
Academic / other
Drugs / interventionsAtezolizumab, Bevacizumab, immunotherapy
Locations7 sites (Heidelberg, Baden-Wurttemberg and 6 other locations)
StatusRecruiting
StartedJuly 16, 2025
Main results expectedMarch 2028
Study endsMarch 2028
Registry record updatedAugust 6, 2025
Trial IDNCT05690048 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Adults (≥18) with unresectable HCC who are eligible for atezolizumab/bevacizumab, have measurable disease, preserved liver function (Child‑Pugh A or B ≤7), and ECOG 0–1.

Probably not a fit

Patients with prior immune‑checkpoint therapy, active autoimmune or inflammatory disorders, recent immunosuppression, uncontrolled HIV or HBV/HCV co‑infection, or poor liver function/ECOG status are unlikely to qualify or benefit.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

FLORA is a randomized, double-blind, placebo-controlled phase II trial with 2:1 randomization to receive encapsulated fecal microbiota transfer (FMT) or placebo alongside standard atezolizumab/bevacizumab for advanced HCC. Before dosing, participants undergo sigmoidoscopy with mucosal biopsies and receive oral vancomycin or placebo on days -3 to 0 to condition the gut. Encapsulated FMT or placebo is given on day 0 and day 21 concurrent with the first two cycles of atezolizumab/bevacizumab, and a tumor biopsy plus repeat sigmoidoscopy are performed around day 40–42. Safety, immunologic changes in the gut and tumor microenvironment, and radiologic response after four cycles will be measured per protocol.

Why it matters

Potential benefit: If successful, this approach could increase response rates to atezolizumab/bevacizumab and potentially delay disease progression in advanced HCC.

How similar studies have gone: Early reports in melanoma and other solid tumors have shown promising signals that FMT can improve checkpoint inhibitor responses, but randomized data in HCC are limited.

Who can join: the full rules

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Age 18 years or older
2. Confirmed radiologic or histological diagnosis of HCC
3. Disease not amenable to resection, liver transplantation or loco-regionary therapy
4. Eligible for therapy with Atezolizumab / Bevacizumab according to standard of care
5. Measurable disease per RECIST 1.1
6. Preserved liver function with a Child-Pugh score A or B (maximally 7 points)
7. Performance status ECOG 0-1

Exclusion Criteria:

1. Use of immunosuppressive medication within 6 months prior to the first dose of Atezolizumab / Bevacizumab.
2. Active or prior documented autoimmune or inflammatory disorders
3. Prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-VEGF antibodies.
4. Known to have tested positive for human immunodeficiency virus (HIV) infection.
5. Co-infection of HBV and HCV. Subjects with a history of HCV infection but who are negative for HCV RNA by PCR will be considered non-infected with HCV.
6. Evidence by investigator assessment of varices at risk of bleeding on upper endoscopy undertaken within 12 months of randomization.
7. Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow a formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism or excretion of investigational product.
8. Uncontrolled arterial hypertension defined by a systolic pressure \> 150 mm Hg or diastolic pressure \> 90 mm Hg or other hypertensive cardiovascular complications despite standard medical treatment.
9. Any history of nephrotic or nephritic syndrome.
10. Usage of systemic antibiotic therapy within 2 weeks prior to the first dose of Atezolizumab/Bevacizumab.
11. Usage of probiotic products/supplements within 1 week prior to the first dose of Atezolizumab/Bevacizumab.
12. Known fibrolamellar HCC, sarcomatoid HCC, infiltrative-type HCC, or mixed cholangiocarcinoma and HCC.
13. History of another primary malignancy.
14. Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention.
15. Pregnancy or lactation.
16. History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product.
17. Participation in other interventional clinical trials or observation period of competing clinical trials, respectively.
18. Held in an institution by legal or official order.
19. Legally incapacitated.
20. Known hypersensitivity to any component of the vancomycin, atezolizumab or bevacizumab formulation.

Where it's running

  • University Hospital Heidelberg
    Heidelberg, Baden-Wurttemberg, Germany     Recruiting
  • University Hospital Augsburg
    Augsburg, Germany     Not yet recruiting
  • University Hospital Essen
    Essen, Germany     Not yet recruiting
  • University Hospital Mannheim
    Mannheim, Germany     Not yet recruiting
  • University Hospital Regensburg
    Regensburg, Germany     Not yet recruiting
  • University Hospital Tübingen
    Tübingen, Germany     Not yet recruiting
Show 1 more location
  • University Hospital Ulm
    Ulm, Germany     Not yet recruiting

Study contacts

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov ↗ Find more trials like this →
Browse more
Immunotherapy 918HCC - Hepatocellular Carcinoma 41Atezolizumab 105Bevacizumab 273University Hospital Heidelberg 50
Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.