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SNCTP000005279 | DRKS00031297 | BASEC2022-01432

Modulation des Darmmikrobioms in der Krebstherapie

Datenbasis: BASEC (Import vom 11.10.2024), WHO (Import vom 09.10.2024)
Geändert: 21.09.2024, 01:00
Krankheitskategorie: Dickdarm- und Mastdarmkrebs

Zusammenfassende Beschreibung der Studie (Datenquelle: BASEC)

Ziel dieser Studie ist es, den Effekt der Anwendung von kommensalen Bakterien auf die Veränderung der Zusammensetzung des Darmmikrobioms bei Patienten mit Dickdarmkrebs zu untersuchen. Dabei wird die Veränderung des Darmmikrobioms bei Teilnehmern mit unterschiedlichem Krankheitsverlauf systematisch untersucht, um aussagekräftige Ergebnisse über Mikrobiomveränderungen und deren Auswirkungen auf Patienten zu liefern. Die Auswertung bei Patienten kann wertvolle Einblicke in mögliche Wirkungsunterschiede zwischen Krebs-Stadien geben. Im Rahmen dieser Studie wird die Intervention auf sichere Anwendung und auf mögliche (schwerwiegende) unerwünschte Ereignisse getestet, wobei Auswirkungen auf Blut, Stuhl und Lebensqualität berücksichtigt werden. Darüber hinaus wird das Studienpräparat auf mögliche weitere Auswirkungen auf das Wohlbefinden der Patienten evaluiert.

Untersuchte Krankheiten(Datenquelle: BASEC)

Kolon-Karzinom Stadium I-IV

Health conditions (Datenquelle: WHO)

Colorectal Cancer

Seltene Krankheit (Datenquelle: BASEC)

Nein

Untersuchte Intervention (z.B. Medikament, Therapie, Kampagne) (Datenquelle: BASEC)

Einnahme eines Nahrungsergänzungsmittels mit 10 Bakterienstämmen (5*10^9 koloniebildende Einheiten/Beutel)

1 Beutel pro Tag für 24 Wochen

Interventions (Datenquelle: WHO)

Group 1: A probiotic product OMNi-BiOTiC? from the company Allergosan containing a mix of 10 probiotic bacterial strains will be administered orally in lyophilized form. Administration will be applied once daily with one dose equivalent to 5 * 109 colony forming units (cfu), in the morning over a period of 6 months.

Screening-phase will take up to two weeks and will be followed by a treatment period of 24 weeks. In Total 4 visits will be performed: Screening visit between -14 to -1 days before baseline. Treatment duration with probiotic product will be 24 weeks starting at the baseline visit. A study visit will be performed at week 8. End of treatment visit (EOT) takes place at week 24.
At each visit, physical examination takes place and vital signs, questionnaires (quality of life and dietary) as well as adverse events will be documented. At screening visit, study visit and EOT visit serum and whole blood as well as stool samples are collected for further analyses.

Kriterien zur Teilnahme an der Studie (Datenquelle: BASEC)

• Bereit und in der Lage, eine schriftliche Einverständniserklärung/Einwilligung für die Studie abzugeben
• ≥18 Jahre alt
• Bestätigte Diagnose eines Kolon-Karzinoms im Stadium I-IV durch Histologie

Ausschlusskriterien (Datenquelle: BASEC)

• Probanden, die innerhalb von <28 Tagen nach Beginn der Studienvorbereitung mit Chemotherapie, Immuntherapie, biologischer Therapie oder einem anderen Prüfmittel behandelt wurden.
• Alle Zustände, Therapien oder Laboranomalien, die die Ergebnisse der Studie verfälschen, die Teilnahme für die gesamte Dauer der Studie beeinträchtigen oder nach Meinung des Prüfarztes nicht im besten Interesse des Teilnehmers sind
• Antibiotikabehandlung innerhalb von 4 Wochen vor der ersten Dosis

Inclusion/Exclusion Criteria (Datenquelle: WHO)

Gender: All
Maximum age: None
Minimum age: 18 Years
Inclusion criteria: ? Willing and able to provide written informed consent/assent for the trial
? Confirmed diagnosis of stage I-IV CRC by histology
? Have adequate organ function in the opinion of the investigator
? Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
? Toxicity from prior cancer therapy should have been resolved to CTCAE Grade = 1 (excluding alopecia and neuropathy, where up to Grade 2 residual is allowed for up to 6 weeks after end of chemotherapy)
? Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR - Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days corresponding to the time needed to eliminate any study intervention(s) after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. - A WOCBP must have a negative highly sensitive serum pregnancy test at screening visit and thus before the first dose of study intervention. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
? Stage IV patients will have to present a thoracoabdominal CT scan (TACT) or PET-CT scan as well as liver MRI at screening visit that is not older than 6 weeks (performed as part of the regular medical treatment at the end of the adjuvant chemotherapy) as per clinical routine as part of their regular medical treatment according to USZ (ESMO-based) treatment guidelines.
? Stage IV patients will have a TACT, PET-CT and/or liver MRI as per clinical routine as part of their regular medical treatment according to USZ (ESMO-based) treatment guidelines
Exclusion criteria: ? Subjects treated with chemotherapy, immunotherapy, biologic therapy, or other investigational agent within <28 days of starting study product. Continuation of hormone replacement therapy is permitted. Stable regimens of hormonal therapy i.e. for prostate cancer (e.g. leuprolide, a GnRH agonist), ovarian, or breast cancer are not exclusionary.
? Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant?s participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
? Active bacterial infection requiring oral or systemic antibiotic therapy
? Subjects who have completed a course of antibiotics within four weeks prior to first dosing
? Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the trial
? Any medical condition of health disorders that prevents from participating the clinical trial in the opinion of the investigators
? Known HIV infection, or active infection with hepatitis B or C
? Any disease or syndrome causing immunodeficiency in the opinion of the treating investigator
? Additional hematologic or lymphatic malignancies within the last 2 years
? Any disease requiring immunosuppressive or immunomodulatory treatment which makes the patient inapplicably for a participation in the trial in the opinion of the investigator
? Female subjects that are pregnant or breastfeeding
? ECOG status 2-4

Weitere Angaben zur Studie im WHO-Primärregister

http://drks.de/search/en/trial/DRKS00031297

Weitere Angaben zur Studie aus der Datenbank der WHO (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00031297
Weitere Informationen zur Studie

Datum der Studienregistrierung

24.02.2023

Einschluss der ersten teilnehmenden Person

07.02.2023

Rekrutierungsstatus

Recruiting

Wissenschaftlicher Titel (Datenquelle: WHO)

Modulation of the Gut Microbiome for Cancer Therapy

Studientyp (Datenquelle: WHO)

interventional

Design der Studie (Datenquelle: WHO)

Allocation: N/A: single arm study; Masking: Open (masking not used); Control: uncontrolled; Assignment: single; Study design purpose: othe

Phase (Datenquelle: WHO)

N/A

Primäre Endpunkte (Datenquelle: WHO)

Demonstrate a persistent modification of the intestinal microbiome in the feces (stool) of the participants following Bacteria administration as measured by metagenomics analysis by Shotgun Sequencing. Analyses are performed at the beginning of the study, after 8 weeks and at the end of the study after 24 weeks.

Sekundäre Endpunkte (Datenquelle: WHO)

- Safety and feasibility of Bacteria will be assessed by measuring incidence of adverse events. Adverse events will be assessed as per CTCAE v5.0 at each study visit.
- Detection of study product (Bacteria) in stool as measured by metagenomics analysis by Shotgun Sequencing of stool samples taken at screening visit, study visit and EOT visit.
- Alterations in serum metabolome composition in serum following study product (Bacteria) application as measured by HD-MS analysis (screening visit, study visit and EOT visit)
- Alterations in fecal metabolome composition in feces (stool) following study product (Bacteria) application as measured by HD-MS analysis of stool samples taken at screening visit, study visit and EOT visit.
- Alterations in immune cell composition in peripheral blood following study product (Bacteria) application as measured by single cell RNAsequencing and/or HD-FACS/CyTEK of peripheral blood mononuclear cells (screening visit, study visit and EOT visit)
- Alterations in immune cell composition in the intestine following study product (Bacteria) application as measured by single cell RNAsequencing. Imaging mass cytometry, immunostaining and/or FACS of intestinal tissue biopsies obtained by sigmoidoscopy at baseline and at EOT visit.
- Increase in number and quality of circulating T-cells in peripheral blood following study product (Bacteria) application assessed by single cell RNAsequencing and/or FACS. This feature has been directly correlated with better prognosis. (screening visit, study visit and EOT visit)
- Alterations in immune cell composition in the tumor tissue (primary tumor) following study product (Bacteria) application as measured by single cell RNA sequencing. Imaging mass cytometry, immunostaining and/or at baseline and at EOT visit.
- Alterations in levels of serum cytokines, growth factors following study product (Bacteria) application as determined by Multiplex ELISA from serum (screening visit, study visit and EOT visit)
- Serum level of CEA as clinically relevant tumor marker for CRC (screening visit, study visit and EOT visit)
- Improvement in health-related quality of life: HRQL will be assessed at baseline and in weeks 8 and 24 using the EuroQol Health questionnaire instrument EQ-5D-5L.
- Clinical efficacy: Assessment of tumor size in stage IV patients with measurable disease by TACT scan according to iRECIST criteria at EOT visit compared to baseline.
- Clinical efficacy: Assessment of time to relapse in stage I-III patients by TACT, PET-CT scan and or MRI liver (in stage IV patients) at EOT visit compared to baseline.
- It must be emphasized that the tumor size alone will not be a sufficient read-out for tumor development using imaging approaches. Since our bacteria are regarded as cancer immunotherapy, an increase in tumor size as assessed by TACT scan is often observed. Thus, the correlation to the molecular analyses of the tumor tissue (available via liver biopsy) will be important. Here, it will be expected that a strong increase in infiltrating immune cells, particularly T-cells, will be present. The combination of the CT data and the molecular tissue data will be important for the clinical efficacy read-out in stage IV patients with measurable disease.

Kontakt für Auskünfte (Datenquelle: WHO)

Institut Allergosan Pharmazeutische Produkte Forschungs- und Vertriebs GmbH

Ergebnisse der Studie (Datenquelle: WHO)

Zusammenfassung der Ergebnisse

noch keine Angaben verfügbar

Link zu den Ergebnissen im Primärregister

http://drks.de/search/en/trial/DRKS00031297#studyResults

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten

No

Studiendurchführungsorte

Durchführungsorte in der Schweiz (Datenquelle: BASEC)

Zürich

Durchführungsländer (Datenquelle: WHO)

Switzerland

Kontakt für weitere Auskünfte zur Studie

Angaben zur Kontaktperson in der Schweiz (Datenquelle: BASEC)

Prof. Dr. med. Michael Scharl
+ 41 44 255 3419
michael.scharl@usz.ch

Kontakt für allgemeine Auskünfte (Datenquelle: WHO)

Gmeinstra?e 13
Institut Allergosan Pharmazeutische Produkte Forschungs- und Vertriebs GmbH
+43 316 405 305 103
kolleritsch@allergosan.at

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

Michael
Scharl
R?mistrasse 100
Klinik f?r Gastroenterologie und Hepatologie - Universit?tsspital Z?rich
+41 44 255 85 48
Michael.Scharl@usz.ch

Bewilligung durch Ethikkommission (Datenquelle: BASEC)

Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)

Kantonale Ethikkommission Zürich

Datum der Bewilligung durch die Ethikkommission

20.12.2022

Weitere Studienidentifikationsnummern

Studienidentifikationsnummer der Ethikkommission (BASEC-ID) (Datenquelle: BASEC)

2022-01432
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