Fecal Microbiota Transplantation to RESCUE Patients With Unresectable Hcc Progressors to First Line Therapy With AtezolizUmaB and Bevacizumab

NCT07276100 | Recruiting Phase 2 DMC

• 2 other identifiers: RESCUE-HUB2023-510504-45-00
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate whether fecal microbiota transplantation (FMT), when administered in combination with atezolizumab and bevacizumab, can improve treatment response in participants with hepatocellular carcinoma (HCC) whose disease has progressed during prior atezolizumab-bevacizumab therapy. The study will also assess the safety and feasibility of this treatment strategy. Primary Objective: To determine whether FMT can restore or enhance response to atezolizumab and bevacizumab following disease progression. Participants will: Receive a fecal microbiota transplantation (FMT). Resume treatment with atezolizumab and bevacizumab, administered every 3 weeks.

Conditions

Hepato Cellular Carcinoma (HCC)

Keywords

hepato cellular carcinoma; atezolizumab; microbiota; fecal microbiota trasplant

Outcome Measures

Primary Outcomes (2)

• incidence of adverse events of grade > 3

  through study completion, approximately 3 years

• disease control rate

  12 weeks after FMT

Study Arms (1)

experimental

EXPERIMENTAL

Fecal microbiota transplantation (FMT) + atezolizumab (1200 mg flat dose) and bevacizumab (15 mg/kg) Q3W

Other: Fecal microbiota transplantation (FMT); Drug: Atezolizumab & Bevacizumab

Interventions

Fecal microbiota transplantation (FMT) OTHER

Fecal microbiota transplantation (FMT)

experimental

Atezolizumab & Bevacizumab DRUG

Atezolizumab \& Bevacizumab

experimental

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.
• Tolerance to first-line treatment for HCC with atezolizumab plus bevacizumab, defined as absence of adverse events requiring permanent discontinuation of either drug.
• Ability to comply with all study procedures, in the investigator's judgment.
• Unresectable hepatocellular carcinoma with early disease progression on first-line atezolizumab + bevacizumab (within 4 months of treatment initiation).
• At least one untreated measurable lesion per RECIST 1.1.
• ECOG Performance Status 0-1.
• Child-Pugh class A.
• Adequate hematologic and end-organ function (laboratory values obtained within 7 days prior to enrollment), defined as follows:
• ANC ≥ 1.5 × 10⁹/L (1500/µL), without G-CSF support.
• Lymphocyte count ≥ 0.5 × 10⁹/L (500/µL).
• Platelet count ≥ 60 × 10⁹/L (60,000/µL), without transfusion.
• Hemoglobin ≥ 90 g/L (9 g/dL); transfusion allowed if last transfusion ≥ 3 weeks prior.
• AST, ALT, and ALP ≤ 5 × ULN.
• Total bilirubin ≤ 3 × ULN.

You may not qualify if:

• \. History of leptomeningeal disease or brain metastases.
• \. Active or prior autoimmune disease or immune deficiency (e.g., myasthenia gravis, myositis, autoimmune hepatitis, SLE, RA, IBD, antiphospholipid syndrome, Wegener, Sjögren, Guillain-Barré, MS), except:
• Autoimmune hypothyroidism on replacement therapy.
• Controlled Type 1 diabetes on insulin.
• Dermatologic-only autoimmune diseases (eczema, psoriasis, lichen simplex chronicus, vitiligo) if:
• \. Rash \<10% BSA. 2. Well-controlled on low-potency topical steroids. 3. No exacerbations requiring systemic therapy within 12 months.
• \. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on CT (radiation pneumonitis in field allowed).
• \. Active tuberculosis.
• \. Significant cardiovascular disease within 3 months (NYHA ≥ II, MI, CVA), unstable arrhythmia, or unstable angina.
• \. Congenital long-QT syndrome or QTcF \>500 ms at screening.
• \. Active advanced malignancy other than HCC within 1 year.
• \. Prior severe adverse reaction to atezolizumab or bevacizumab unmanageable with low-dose steroids or requiring discontinuation.
• \. Uncorrectable electrolyte abnormalities (K, Ca, Mg).
• \. Major surgery within 4 weeks or planned major surgery during study.
• \. Severe infection within 4 weeks (including hospitalization, bacteremia, severe pneumonia).

Sponsors & Collaborators

• IRCCS Azienda Ospedaliero-Universitaria di Bologna: lead

Study Sites (1)

IRCCS AOU di Bologna Policlinico di Sant'Orsola

Bologna, BO, 40138, Italy

RECRUITING

MeSH Terms

Interventions

Fecal Microbiota Transplantation; atezolizumab; Bevacizumab

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Fabio Piscaglia, MD

CONTACT

0512142214; fabio.piscaglia@unibo.it

Mariarosaria Marseglia Biologist, Biologist

CONTACT

mariarosaria.marseglia@aosp.bo.it

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: Head of Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Clinical Professor

Study Record Dates

• First Submitted: November 25, 2025
• First Posted: December 10, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029
• Last Updated: December 10, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)