Modulation of the gut microbiome in cancer therapy

ICTRP Trial ID
DRKS00031297 (ICTRP)

Official title (approved by ethics committee)
Modulation (BASEC)

Academic title
Modulation of the Gut Microbiome for Cancer Therapy (ICTRP)

Public title
Modulation of the Gut Microbiome for Cancer Therapy (ICTRP)

Disease under investigation
Colorectal Cancer (ICTRP)

Intervention under investigation
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. (ICTRP)

Type of trial
interventional (ICTRP)

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

Inclusion/Exclusion criteria
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 (ICTRP)

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 participants 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

Primary and secondary end points
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. (ICTRP)

- 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. (ICTRP)

Registration date
24.02.2023 (ICTRP)

Incorporation of the first participant
07.02.2023 (ICTRP)

Secondary sponsors
not available

Additional contacts
kolleritsch@allergosan.at, +43 316 405 305 103, Institut Allergosan Pharmazeutische Produkte Forschungs- und Vertriebs GmbH (ICTRP)

Secondary trial IDs
not available

Results-Individual Participant Data (IPD)
No (ICTRP)

Further information on the trial
http://drks.de/search/en/trial/DRKS00031297 (ICTRP)