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

NCT05273255 | Completed DMC

• 1 other identifier: FMT-Malignancies
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Cancer; Fecal Microbiota Transplantation; Immune Checkpoint Inhibitors; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Change in the intestinal microbiome community

  Mean change from baseline of bacterial species compared with 24 weeks post fecal microbiota transplantation (FMT).

  up to 24 weeks

Secondary Outcomes (7)

• Adverse Events Related to Study Intervention

  up to 24 weeks

• Objective Response Rate

  up to 24 weeks

• Progression-Free Survival

  up to 24 weeks

• Overall Survival

  up to 24 weeks

• Correlation between specific immune cell presence in blood/colon tissue and therapy response

  up to 24 weeks

Study Arms (1)

FMT-Recipients

EXPERIMENTAL

FMT-Recipients are patients with stage IV cancer, who have not sufficiently responded (stable disease or non-response) after at least 1 full cycle of CI. These patients will undergo the FMT procedure after the colon cleansing performed per routine treatment protocols at the Departement of Gastroenterology at the University Hospital of Zürich. The stool is donated by FMT-Donors, which are patients with any solid cancer stage III or IV cancers, who received any ICI-Therapy and have experienced a durable partial or complete response. FMT infusate will be administered via colonoscopy.

Biological: Fecal Microbiota Transplantation (FMT)

Interventions

Fecal Microbiota Transplantation (FMT) BIOLOGICAL

Single-dose of fecal microbiota from FMT-Donor transplanted endoscopically to FMT-Recipient in between two cycles of CI.

FMT-Recipients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patients with refractory malignancy (FMT-Recipients). The investigators will recruit 25 individuals with stable or progressing disease after minimum of 1 cycle of CI.
• Patients with malignancy in remission after ICI therapy (FMT-Donors). The investigators will recruit 5 patients willing to donate stool samples for the study.
• Histologically or cytologically confirmed diagnosis of malignancy
• Currently treated with CI with at least 1 cycle completed. Multiple active malignancies are allowed.
• 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).
• 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.
• Willingness to receive FMT administered via colonoscopy and undergo necessary bowel preparation pre-procedure.
• 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

You may not qualify if:

• Presence of absolute contra-indications to colonoscopy and/or FMT administration:
• Toxic megacolon
• Inflammatory bowel disease
• Anatomic contra-indications to colonoscopy
• Colectomy
• 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.
• Currently under any form of systemic antibiotics.
• 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).
• Severe anaphylactic reaction to any food (food allergies).
• Had a severe hypersensitivity reaction to propofol.
• Has serious concomitant illnesses. The eligibility can be granted by the treating investigator on individual bases.
• Has HIV infection or AIDS-related illness.
• 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.
• 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.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Sponsors & Collaborators

• Michael Scharl: lead

Study Sites (1)

University of Zurich, University Hospital Zurich

Zurich, Switzerland

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Fecal Microbiota Transplantation

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Michael Scharl, Prof. Dr.

  University Hospital Zurich, University of Zurich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: February 14, 2022
• First Posted: March 10, 2022
• Study Start: March 14, 2022
• Primary Completion: January 4, 2024
• Study Completion: October 24, 2024
• Last Updated: March 28, 2025

Record last verified: 2025-03

Locations

CH (1)