Role of the Gut Microbiome in Anti-tumor Therapy Induced Diarrhea

Studien-Informationen Einschlusskriterien Studien-Rationale

Rekrutierend

NCT-Nummer:
NCT05873231

Studienbeginn:
April 2021

Letztes Update:
22.06.2023

Wirkstoff:
-

Indikation (Clinical Trials):
Diarrhea

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Medical University of Graz

Collaborator:
-

Studienlocations
(1 von 1)

Department of Internal Medicine, Medical University of Graz
8010 Graz
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Vanessa Stadlbauer, MD
Phone: 0043316385
Phone (ext.): 82282
E-Mail: vanessa.stadlbauer@medunigraz.at» Ansprechpartner anzeigen

Studien-Informationen

Detailed Description:

Hepatocellular carcinoma (HCC) is the 5th most common tumor worldwide and the second most

frequent cause of cancer-related death globally. HCC represents about 90% of primary liver

cancers and constitutes a major global health problem.Therapeutic approaches depend on the

stage of the disease. In the last decade systemic therapy approaches complement surgical and

locoregional treatment in advanced disease stages.

The current first-line drug class used to treat locally advanced and metastasized HCC are

tyrosine kinase inhibitors (TKIs). At the moment the multikinase inhibitors sorafenib,

lenvatinib and regorafenib are licensed in Austria for treatment of HCC: TKIs are a class of

small molecule drugs that block the intracellular signals which drive proliferation in many

malignant cells by specifically inhibiting the kinase function of individual intracellular

pathways involved in receptor-mediated growth signaling.Diarrhea is one of the most common

side effects of TKIs, that often prevents optimal dosage and thereby limits efficacy of

systemic cancer therapy. Mechanisms of TKI induced diarrhea are largely unknown, speculations

span from induction of exocrine pancreatic insufficiency leading to vitamin malabsorption and

hypophosphatemia to enterocyte malfunction. Recently, accumulating data suggest that the

composition of gut microbiome may also affect efficacy and toxicity of cancer therapy. In a

small pilot study (n=25) patients who did not develop diarrhea under TKI had a higher

abundance of Butyricimonas and a lower abundance of Citrobacter, Peptostreptococcus, and

Staphylococcaceae. To the best of our knowledge, microbiome composition in patients with TKI

induced diarrhea has not been studied in detail yet. However, this information is of clinical

relevance since the manipulation of the gut microbiota through antibiotics, probiotics,

prebiotics or fecal transplantation is an interesting strategy to improve efficacy and

mitigate toxicity of anticancer drugs such as TKI. Probiotics for example have been shown to

be able to prevent and treat diarrhea and may therefore be a valuable option to prevent or

treat TKI-induced side effects.

In 2019 around 5000 Austrian citizens were diagnosed with lung cancer. The diagnosis is

associated with a very poor prognosis compared to other malignant diseases. However, the

introduction of checkpoint inhibitors has led to a revolutionary improvement in prognosis for

those that respond.

Immune-Checkpoints are immunologic pathways that are used by tumor cells to evade destruction

by immune cells. The most important checkpoints to date are programmed death ligand 1

(PDL-1), cytotoxic T lymphocyte antigen-4 (CTLA-4) and TIGIT. Antagonization of these check

points by monoclonal antibodys can largely improve antineoplastic efficacy of immune cells.

These immune checkpoint inhibitors (ICI) are essential part of modern neoadjuvant, adjuvant

and palliative oncologic therapy concepts. ICI-treatment may lead to remarkable responses.

However, 60 to 80 percent of patients do not respond to therapy.Although Tumor-PDL-1 level

has shown some predictive value and is therefore used in clinical praxis it cannot predict

response reliably.

Many preclinical and clinical trials showed evidence of relevant impact of the composition of

the microbiome of the gut and response to ICI. Therefore, the microbiome of the gut may be

promising biomarker and even possible target for intervention to predict and improve ICI

response in the future. However, the exact optimal composition of the gut microbiome and the

strategies for intervention are still unclear.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- 18 years or older

- Start of a systemic anti-cancer therapy

- Informed consent

Exclusion Criteria:

- • Pre-existing diarrhoea

- Antibiotic therapy -4 to -1 week before inclusion

- Probiotic treatment -4 to -1 week before inclusion

- Inability to give informed consent

Studien-Rationale

Primary outcome:

1. gut microbiome composition (Time Frame - 4-12 weeks):
16s sequencing

Secondary outcome:

1. stool zonulin (Time Frame - 4-12 weeks):
ELISA

2. stool calprotectin (Time Frame - 4-12 weeks):
ELISA

3. serum lipopolysaccharide binding protein (Time Frame - 4-12 weeks):
ELISA

4. serum soluble cluster of differentiation (CD)14 (Time Frame - 4-12 weeks):
ELISA

5. Bristol stool scale (BSS) (Time Frame - 4-12 weeks):
questionnaire on stool consistency and frequency, 1-7, 3-4 is normal

6. gastrointestinal quality of life (GIQLI) (Time Frame - 4-12 weeks):
questionnaire on gastrointestinal quality of life, 0-144, higher scores are better

Quelle: ClinicalTrials.gov

Sie können folgenden Inhalt einem Kollegen empfehlen:

"Role of the Gut Microbiome in Anti-tumor Therapy Induced Diarrhea"

Bitte tragen Sie auch die Absenderdaten vollständig ein, damit Sie der Empfänger erkennen kann.

Die mit (*) gekennzeichneten Angaben müssen eingetragen werden!