JOURNAL ONKOLOGIE – STUDIE

Fecal Microbiota Transplantation in Patients With Malignancies Not Responding to Cancer Immunotherapy

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05273255

Studienbeginn:
März 2022

Letztes Update:
02.02.2024

Wirkstoff:
Fecal Microbiota Transplantation (FMT)

Indikation (Clinical Trials):
Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Michael Scharl

Collaborator:
-

Studienleiter

Michael Scharl, Prof. Dr.
Principal Investigator
University Hospital Zurich, University of Zurich

Kontakt

Michael Scharl, Prof. Dr.
Kontakt:
Phone: +41 44 255 3419
E-Mail: michael.scharl@usz.ch» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

University of Zurich, University Hospital Zurich
Zurich
SwitzerlandRekrutierend» Google-Maps
Ansprechpartner:
Michael Scharl
E-Mail: michael.scharl@usz.ch» Ansprechpartner anzeigen

Studien-Informationen

Brief Summary:

The intestinal microbiome forms a symbiotic relationship with the human host and continuously

interacts with its immune system. Specific compositions of the intestinal microbiome in

patients with cancer have been linked to the response to therapy with cancer immunotherapies

(CI), such as immune checkpoint inhibitors (ICIs). The investigators hypothesize that fecal

microbiota transplantation (FMT) from patients being responsive to ICI therapy (FMT-Donor)

can modulate the intestinal microbiome of patients with CI-refractory malignancies

(FMT-Recipients) and render them into responders. Successful proof-of-concept studies showed

that reversion from an ICI non-responsive to a responsive disease is indeed possible in

melanoma patients after FMT. This trial expands the FMT intervention to patients with any

malignancy treated with cancer immunotherapy as a standard of care, to demonstrate the

feasibility of this FMT approach as a novel option in cancer therapy.

Ein-/Ausschlusskriterien

General inclusion criteria for all participants:

- Patients, at minimum 18 years of age, male or female

- Signed informed consent obtained from subject according to local regulations

- ECOG score at the time of study enrolment 0-1

The investigators will include patients/individuals fulfilling inclusion criteria for one

of the following groups:

1. Patients with refractory malignancy (FMT-Recipients). The investigators will recruit

25 individuals with stable or progressing disease after minimum of 1 cycle of CI.

2. Patients with malignancy in remission after ICI therapy (FMT-Donors). The

investigators will recruit 5 patients willing to donate stool samples for the study.

Inclusion criteria FMT-Recipients:

1. Histologically or cytologically confirmed diagnosis of malignancy

2. Currently treated with CI with at least 1 cycle completed. Multiple active

malignancies are allowed.

3. Patient with stable or progressive disease as shown at the most recent staging method

and decided by the treating investigator (based on the radiologic assessment).

4. Must be CI refractory/resistant as judged by the treating physician based on a recent

CT or PET-CT (PET-MRI) scan not older than 8 weeks before screening visit.

5. Willingness to receive FMT administered via colonoscopy and undergo necessary bowel

preparation pre-procedure.

6. Demonstrate adequate organ function as defined below, all screening labs should be

performed within 28 days of FMT intervention.

Following laboratory parameters need to be met:

- Platelet count ≥ 50 x 10^9 / L

- Hemoglobin ≥ 8.5 g/dL

- Prothrombin time (PT)-international normalized ration (INR) ≤ 1.5

7. Female subject of childbearing potential should have a negative urine pregnancy within

minimum 8 hours prior to receiving the study intervention (FMT). If the urine test is

positive or cannot be confirmed as negative, a serum pregnancy test will be required.

8. Female subjects of childbearing potential must be willing to use a clinically

established method of contraception before the FMT procedure.

Inclusion criteria FMT-Donors:

1. Documented history of malignancy treated with ICI therapy.

2. Featuring partial or complete response of the malignancy as assessed by radiologic

examination with a minimum duration of remission lasting ≥12 months measured since

initiation of therapy.

3. Willingness to complete donor-specific questionnaire.

4. Willingness to complete donor-specific serologic and stool testing to evaluate

infectious agents.

5. Patient tested negatively for all infectious agents specified.

6. Willingness to provide multiple stool samples, until total amount reaches 170g.

7. Absence of major gastrointestinal symptoms 3 months prior to stool donation (including

frequent vomiting, diarrhea, bleeding, constipation).

Exclusion criteria FMT Recipients:

1. Presence of absolute contra-indications to colonoscopy and/or FMT administration:

- Toxic megacolon

- Inflammatory bowel disease

- Anatomic contra-indications to colonoscopy

- Colectomy

2. Patient is currently participating and receiving other study therapy or has

participated in a study of an investigational agent and received study therapy or used

an investigational device within 4 weeks of this study intervention.

3. Currently under any form of systemic antibiotics.

4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (> 10 mg

prednisone daily or equivalent) or any other form of immunosuppressive therapy two

weeks prior to trial treatment. Patients receiving systemic steroids at physiologic

doses are permitted to enroll assuming steroid dose is not above the acceptable

threshold (> 10 mg prednisone daily or equivalent).

5. Severe anaphylactic reaction to any food (food allergies).

6. Had a severe hypersensitivity reaction to propofol.

7. Has serious concomitant illnesses. The eligibility can be granted by the treating

investigator on individual bases.

8. Has HIV infection or AIDS-related illness.

9. Has active infection of HAV, HBV or HCV. Patients with a history of Hepatitis B/C

infection who have received anti-viral therapy and are disease free may be considered

for enrollment after discussion with Principal Investigator.

10. Patient has received a live vaccine within 4 weeks prior to the first dose of

treatment. Seasonal influenza vaccines or COVID-19 vaccines for injection are

generally inactivated virus vaccines and are allowed.

11. Has known psychiatric or substance abuse disorders that would interfere with

cooperation with the requirements of the trial.

12. Females who are pregnant or breastfeeding.

13. Active central nervous system (CNS) metastases and/or leptomeningeal involvement.

Exclusion criteria FMT Donors:

1. History or current antibiotic treatment during the 2 month preceding donation.

2. History or current intrinsic gastrointestinal illnesses, including inflammatory bowel

disease, irritable bowel syndrome, chronic diarrheal disorder (e.g. celiac disease or

microscopic colitis) or major gastrointestinal surgical procedures.

3. History or current symptomatic autoimmune illness.

4. History or current documented neurologic or neurodevelopmental disorders.

5. History or current metabolic syndrome, obesity (BMI of >35), or moderate-to-severe

malnutrition (as assessed clinically).

6. History or current infection with HIV (or AIDS-related illness).

7. Positive serological tests for Syphilis, HAV, HBV or HCV.

8. Positive stool test for Escherichia coli, Vancomycin-resistant Enterococcus,

Norovirus, C. difficile, Yersinia, Campylobacter, Shigella or Salmonella.

9. Positive stool test for parasites.

10. Positive Sars-CoV-2 screening/testing (active infection).

Subjects whose pregnancy test on Screening visit shows a positive result, have to be

excluded from the study. All pregnancies occurring during the treatment phase of the study

and within 30 days after discontinuation of study medication have to be reported to the

Investigator-Sponsor within one working day of the investigational sites knowledge of the

pregnancy on the Initial Pregnancy Report Form. Female Subjects should be informed in this

way before signing the informed consent form. Female partners of male participants may get

pregnant without any consequence to the male participant.

Studien-Rationale

Primary outcome:

1. Change in the intestinal microbiome community (Time Frame - up to 24 weeks):
Mean change from baseline of bacterial species compared with 24 weeks post fecal microbiota transplantation (FMT).

Secondary outcome:

1. Adverse Events Related to Study Intervention (Time Frame - up to 24 weeks):
Number of adverse events and serious adverse events related definitely to fecal microbiota transplantation (FMT).

2. Objective Response Rate (Time Frame - up to 24 weeks):
Percentage of participants that achieved an objective response as per Response Evaluation Criteria in Solid Tumours (iRECIST) treated with immunotherapy.

3. Progression-Free Survival (Time Frame - up to 24 weeks):
Time, measured in days, between the fecal microbiota transplantation (FMT) and disease progression as per Response Evaluation Criteria in Solid Tumours (iRECIST) treated with immunotherapy.

4. Overall Survival (Time Frame - up to 24 weeks):
The length of time (in days) from study intervention that participants remain alive.

5. Correlation between specific immune cell presence in blood/colon tissue and therapy response (Time Frame - up to 24 weeks):
Number of immune cells in peripheral blood, intestinal and tumor tissue at the time of stool donation, baseline and after 24 weeks post fecal microbiota transplantation (FMT).

6. CI response rate upon microbiome change (Time Frame - up to 24 weeks):
Number of participants with specific bacteria species that positively correlate with the favorable response to cancer immunotherapy.

7. Quality of life based on the questionnaire (Time Frame - up to 24 weeks):
Scoring based on "European Organization for Research and Treatment of Cancer 30-item quality of life questionnaire (EORTC QLQ C-30)".

Geprüfte Regime

Fecal Microbiota Transplantation (FMT):
Single-dose of fecal microbiota from FMT-Donor transplanted endoscopically to FMT-Recipient in between two cycles of CI.

Quelle: ClinicalTrials.gov

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