JOURNAL ONKOLOGIE – STUDIE

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

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05750030

Studienbeginn:
Mai 2023

Letztes Update:
14.09.2023

Wirkstoff:
-

Indikation (Clinical Trials):
Carcinoma, Carcinoma, Hepatocellular

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Medical University of Vienna

Collaborator:
-

Studienleiter

Matthias Pinter, MD PhD
Principal Investigator
Medical University of Vienna, Internal Medicine III, Department of Gastroenterology and Hepatology

Kontakt

Matthias Pinter, MD PhD
Kontakt:
Phone: +43140400
Phone (ext.): 65890
E-Mail: matthias.pinter@meduniwien.ac.at» Kontaktdaten anzeigen

Katharina Pomej, MD
Kontakt:
Phone: +43140400
Phone (ext.): 65890
E-Mail: katharina.pomej@meduniwien.ac.at» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

Medical University of Vienna
1090 Vienna
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Matthias Pinter, MD PhD
Phone: +43140400
Phone (ext.): 65890
E-Mail: matthias.pinter@meduniwien.ac.at» Ansprechpartner anzeigen

Studien-Informationen

Detailed Description:

The main purpose of this phase IIa pilot study is to test the safety and efficacy of fecal

microbiota transplant (FMT) combined with atezolizumab plus bevacizumab in patients who

failed to respond to prior immunotherapy for advanced hepatocellular carcinoma (aHCC).

The primary objective is to assess the safety of FMT combined with atezolizumab plus

bevacizumab, as measured by incidence and severity of treatment-related adverse events.

The secondary objectives are to assess the efficacy of FMT in combination with atezolizumab

plus bevacizumab as measured by best radiological response, objective response rate (ORR),

disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).

Furthermore, the objective is to evaluate the impact of FMT with atezolizumab plus

bevacizumab on the quality of life, as assessed by EQ-5D-5L questionnaires.

Finally, this study also aims to assess the following exploratory endpoints:

- the effect of FMT on recipient gut microbiota composition, diversity, rate of change

from baseline, and similarity to donor stool composition over time (compared between

responders and non-responders)

- the effect of FMT on immune activity in the gut

- metagenome assemblies and functional profiling before and after FMT

- single cell analyses of circulating immune cells before and after FMT

- serum and stool metabolomic and lipidomic signatures before and after FMT

This is a phase IIa, single-center, open-label pilot study. Twelve patients suffering from

advanced-stage hepatocellular carcinoma will be enrolled in this trial. The planned duration

for this study are 48 months.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- 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 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

- Platelet count ≥ 50 G/L

- Leukocytes ≥ 2.5 G/L

- Patients not receiving therapeutic anticoagulation: INR ≤ 2.3 or thromboplastin time ≥

40%

- Women of childbearing potential must agree to remain abstinent (refrain from

heterosexual intercourse) or use contraceptive methods

- Men must agree to remain abstinent (refrain from heterosexual intercourse) or use a

condom

Exclusion Criteria:

- 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

- Significant cardiovascular disease (such as New York Heart Association Class II or

greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3

months prior to study inclusion or unstable angina

- Severe infection within 4 weeks prior to study inclusion

- 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

- Significant vascular disease (e.g., peripheral arterial thrombosis) within 6 months

prior to study inclusion

- Major surgery within 4 weeks prior to study inclusion or minor surgery (excluding

placement of a vascular access device) within 3 days prior to study inclusion

- History of gastrointestinal fistula or perforation, or intraabdominal abscess within 6

months prior to study inclusion

- Serious, non-healing wound or active ulcer

Studien-Rationale

Primary outcome:

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. (Time Frame - 24 months)

Secondary outcome:

1. 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. (Time Frame - 24 months)

2. 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. (Time Frame - 24 months)

3. Efficacy as assessed by progression-free survival (PFS) and overall survival (OS). (Time Frame - 24 months)

4. Quality of life (QoL) as assessed by the patient-reported outcome EQ-5D-5L (European Quality of Life 5 Dimensions 3 Level Version) questionnaire. (Time Frame - 24 months)

Geprüfte Regime

FMT combined with Atezolizumab plus Bevacizumab:
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.

Quelle: ClinicalTrials.gov

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