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

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

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Studienbeginn:
Januar 2024

Letztes Update:
23.01.2023

Wirkstoff:
Fecal microbiota transfer, Vancomycin Oral Capsule, Atezolizumab + Bevacizumab, Placebo Vancomycin Oral Capsule, Placebo Fecal microbiota transfer

Indikation (Clinical Trials):
Liver Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Michael Dill

Collaborator:
National Center for Tumor Diseases, Heidelberg, German Cancer Research Center, Heidelberg University, University of Cologne, Universitätsmedizin Mannheim,

Kontakt

Michael T Dill, PhD
Kontakt:
Phone: 06221 568611
E-Mail: michael.dill@med.uni-heidelberg.de» Kontaktdaten anzeigen

Conrad Rauber, MD/PhD
Kontakt:
Phone: 06221568611
E-Mail: conrad.rauber@med.uni-heidelberg.de» Kontaktdaten anzeigen

Studienlocations
(2 von 2)

University Hospital Heidelberg
69120 Heidelberg
(Baden-Württemberg)
Germany» Google-Maps
Ansprechpartner:
Michael Dill, PhD

Conrad Rauber, PhD» Ansprechpartner anzeigen

University Hospital Heidelberg
69120 Heidelberg
(Baden-Württemberg)
Germany» Google-Maps

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. Differential tumoral CD8 T-cell infiltration (Time Frame - 6 weeks after treatment initiation):
Tumoral CD8 T-cells in IHC before treatment initiation and 6 weeks after (CD8-cells/area of tumor tissue in formalin embedded tumor tissue)

2. Adverse event documentation of FMT in advanced HCC (Time Frame - Follow up 3 months after treatment initiation):
Adverse event documentation [AE] & immune-related adverse events [irAE])

Secondary outcome:

1. Progression-free survival (PFS) (Time Frame - Follow up 3 months after treatment initiation):
Progression-free survival as by RECIST1.1 criteria

2. Overall survival (OS) (Time Frame - Follow up 12 months after treatment initiation):
Overall survival

3. Change of Hepatic function (Time Frame - Follow up 3 months after treatment initiation):
Assessment of Model of End-Stage Liver Disease Score in blood (MELD-Score, 6-40, higher score refers to worse hepatic function)

Studien-Arme

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

Geprüfte Regime

Fecal microbiota transfer (FMT):
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 (A/B):
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.

Quelle: ClinicalTrials.gov

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