Fecal Microbiota Transplantation to Improve Efficacy of Immune Checkpoint Inhibitors in Renal Cell Carcinoma (TACITO)

September 4, 2025 updated by: IANIRO GIANLUCA, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Targeting Gut Microbiota to Improve Efficacy of Immune Checkpoint Inhibitors in Patients With Advanced Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the sixth most common cancer in men and the eighth in women in the USA. In Italy RCC incidence was 11500 new cases in 2017, while mortality was 3371 cases in 2015. Increasing evidence suggests that response to immune checkpoint inhibitors (ICIs), a novel treatment for advanced RCC (aRCC) and other epithelial tumors, can be influenced by the patient gut microbiota. Fecal microbiota transplantation (FMT) is a novel therapeutic option based on the restoration of healthy gut microbiota, and is the most effective therapy for recurrent C. difficile infection, and preliminary nonrandomized findings show that FMT is able to improve efficacy of ICIs in patients with advanced melanoma. The aim of this study is to evaluate, through a randomized controlled trial, the efficacy of targeted FMT (from donors who are responding to ICI. in improving response rates to ICIs in subjects with aRCC.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Renal cell carcinoma (RCC) is the sixth most common cancer in men and the eighth in women in the USA. In Italy RCC incidence was 11500 new cases in 2017, while mortality was 3371 cases in 2015. Increasing evidence suggests that response to immune checkpoint inhibitors (ICIs), a novel treatment for advanced RCC (aRCC) and other epithelial tumors, can be influenced by the patient gut microbiota. Fecal microbiota transplantation (FMT) is a novel therapeutic option based on the restoration of healthy gut microbiota, and is the most effective therapy for recurrent C. difficile infection, and preliminary nonrandomized findings show that FMT is able to improve efficacy of ICIs in patients with advanced melanoma. The aim of the study is to evaluate, through a randomized controlled trial, the efficacy of targeted FMT (from donors who are responding to ICI) in improving response rates to ICIs in subjects with aRCC. So, the investigators will investigate, through a randomized controlled trial, if donor FMT will be more effective than placebo FMT in improving response to ICIs in patients with renal cell carcinoma. Patients will undergo the first infusion by colonoscopy. Then, patients will receive frozen fecal capsules (8 capsules t.i.d.) at 3 and 6 months after the first FMT.

Fifty patients will be enrolled. Sample size calculation was based on the hypothesis of the superiority of FMT+SOC over SOC alone. The 1-year PFS rate for SOC has been reported to be nearly 60%. The alternative hypothesis is that FMT can improve the 1-year PFS rate from 60% to 80% wen associated to SOC. A total of 50 patients will enter this two-treatment parallel-design study. The probability is 80 percent that the study will detect a treatment difference at a one-sided 5.0 percent significance level, if the true hazard ratio is 0.436. This is based on the assumption that the accrual period will be 36 months and the follow up period will be 36 months and the median survival is 15.1 months. The total number of events will be 37.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Rome
      • Rome, Rome, Italy, 00168
        • Digestive Disease Center
      • Rome, Rome, Italy, 00168
        • Gianluca Ianiro

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically confirmed aRCC
  • Metastatic disease (measurable and not-measurable)
  • Radiological assessment within 8 wks before enrollment
  • Patient eligible to therapy with ICI for aRCC (or started within 8 wks)
  • Ability to provide written informed consent
  • Ability to be compliant with the scheduled procedures

Exclusion Criteria:

  • Major comorbidities
  • Concomitant GI or autoimmune disorders, or HIV, HBV, HCV infection
  • Continuative corticosteroid therapy
  • Previous treatment with systemic immune-suppressants or immune-modulatory drugs
  • Antibiotic therapy within 4 weeks prior to enrollment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Donor FMT
Patients enrolled in this arm will receive donor FMT
Biological: donor FMT
This intervention is represented by the administration, in the recipients' gut, of donor microbiota through FMT
Placebo Comparator: Placebo FMT
Patients enrolled in this arm will receive placebo FMT (that will be made of saline solution)
Other: Placebo FMT
This intervention is represented by the administration, in the recipients' gut, of a placebo through FMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants who will be free from tumor progression, as assessed by RECIST criteria v. 1.1.
Time Frame: 12 months
The investigators will evaluate the number of participants who will be free from tumor progression, as assessed by RECIST criteria v. 1.1., after treatments, at 12 month-follow-up
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants who will obtain a partial or a complete tumor response to immunotherapy, as assessed by RECIST criteria v. 1.1, after treatments
Time Frame: 12 months
The investigators will evaluate the number of participants who will obtain a partial or a complete tumor response to immunotherapy, as assessed by RECIST criteria v. 1.1, after treatments, at 12 month-follow-up
12 months
Number of participants who will die for any reason (overall survival)
Time Frame: 12 months
The investigators will evaluate the number of participants who will die for any reason throughout the study period (12 months)
12 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: 12 months
The number of participants with treatment-related adverse events (assessed by CTCAE v4.0) will be recorded throughout the study period (12 months)
12 months
Number of participants with significant increase in alpha-diversity (assessed by Shannon index) and beta-diversity (assessed by Bray-Curtis dissimilarity) of their gut microbiota after treatments
Time Frame: 12 months
Throughout the study period (12 months) the investigators will evaluate the number of participants with significant increase in alpha-diversity (assessed by Shannon index) and beta-diversity (assessed by Bray-Curtis dissimilarity) of their gut microbiota after treatments, compared with baseline
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Investigators

  • Principal Investigator: Gianluca Ianiro, MD, Fondazione Policlinico Gemelli IRCCS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 18, 2021

Primary Completion (Actual)

December 16, 2024

Study Completion (Actual)

July 28, 2025

Study Registration Dates

First Submitted

February 11, 2021

First Submitted That Met QC Criteria

February 16, 2021

First Posted (Actual)

February 17, 2021

Study Record Updates

Last Update Posted (Estimated)

September 8, 2025

Last Update Submitted That Met QC Criteria

September 4, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2664

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data will be available to other researchers

IPD Sharing Time Frame

data will be available after the completion of the study, for 5 years

IPD Sharing Access Criteria

Data will be given upon request to the PI

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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