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

NCT04758507 | Completed Phase 1

• 1 other identifier: 2664
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Number of participants who will be free from tumor progression, as assessed by RECIST criteria v. 1.1.

  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 Outcomes (4)

• 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

  12 months

• Number of participants who will die for any reason (overall survival)

  12 months

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  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

  12 months

Study Arms (2)

Donor FMT

EXPERIMENTAL

Patients enrolled in this arm will receive donor FMT

Biological: donor FMT

Placebo FMT

PLACEBO COMPARATOR

Patients enrolled in this arm will receive placebo FMT (that will be made of saline solution)

Other: Placebo FMT

Interventions

donor FMT BIOLOGICAL

This intervention is represented by the administration, in the recipients' gut, of donor microbiota through FMT

Donor FMT

Placebo FMT OTHER

This intervention is represented by the administration, in the recipients' gut, of a placebo through FMT

Placebo FMT

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (2)

Digestive Disease Center

Rome, Rome, 00168, Italy

Location

Gianluca Ianiro

Rome, Rome, 00168, Italy

Location

Related Publications (5)

• Ianiro G, Rossi E, Thomas AM, Schinzari G, Masucci L, Quaranta G, Settanni CR, Lopetuso LR, Armanini F, Blanco-Miguez A, Asnicar F, Consolandi C, Iacovelli R, Sanguinetti M, Tortora G, Gasbarrini A, Segata N, Cammarota G. Faecal microbiota transplantation for the treatment of diarrhoea induced by tyrosine-kinase inhibitors in patients with metastatic renal cell carcinoma. Nat Commun. 2020 Aug 28;11(1):4333. doi: 10.1038/s41467-020-18127-y.

  PMID: 32859933 BACKGROUND

• Baruch EN, Youngster I, Ben-Betzalel G, Ortenberg R, Lahat A, Katz L, Adler K, Dick-Necula D, Raskin S, Bloch N, Rotin D, Anafi L, Avivi C, Melnichenko J, Steinberg-Silman Y, Mamtani R, Harati H, Asher N, Shapira-Frommer R, Brosh-Nissimov T, Eshet Y, Ben-Simon S, Ziv O, Khan MAW, Amit M, Ajami NJ, Barshack I, Schachter J, Wargo JA, Koren O, Markel G, Boursi B. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science. 2021 Feb 5;371(6529):602-609. doi: 10.1126/science.abb5920. Epub 2020 Dec 10.

  PMID: 33303685 BACKGROUND

• Davar D, Dzutsev AK, McCulloch JA, Rodrigues RR, Chauvin JM, Morrison RM, Deblasio RN, Menna C, Ding Q, Pagliano O, Zidi B, Zhang S, Badger JH, Vetizou M, Cole AM, Fernandes MR, Prescott S, Costa RGF, Balaji AK, Morgun A, Vujkovic-Cvijin I, Wang H, Borhani AA, Schwartz MB, Dubner HM, Ernst SJ, Rose A, Najjar YG, Belkaid Y, Kirkwood JM, Trinchieri G, Zarour HM. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science. 2021 Feb 5;371(6529):595-602. doi: 10.1126/science.abf3363.

  PMID: 33542131 BACKGROUND

• Cammarota G, Ianiro G, Kelly CR, Mullish BH, Allegretti JR, Kassam Z, Putignani L, Fischer M, Keller JJ, Costello SP, Sokol H, Kump P, Satokari R, Kahn SA, Kao D, Arkkila P, Kuijper EJ, Vehreschild MJG, Pintus C, Lopetuso L, Masucci L, Scaldaferri F, Terveer EM, Nieuwdorp M, Lopez-Sanroman A, Kupcinskas J, Hart A, Tilg H, Gasbarrini A. International consensus conference on stool banking for faecal microbiota transplantation in clinical practice. Gut. 2019 Dec;68(12):2111-2121. doi: 10.1136/gutjnl-2019-319548. Epub 2019 Sep 28.

  PMID: 31563878 BACKGROUND

• Porcari S, Ciccarese C, Heidrich V, Rondinella D, Quaranta G, Severino A, Arduini D, Buti S, Fornarini G, Primi F, Stumbo L, Giannarelli D, Giudice GC, Damassi A, Giron Berrios JR, Puncochar M, Barbazuk TB, Piccinno G, Pinto F, Armanini F, Asnicar F, Schinzari G, Derosa L, Kroemer G, Sanguinetti M, Masucci L, Gasbarrini A, Tortora G, Cammarota G, Zitvogel L, Segata N, Iacovelli R, Ianiro G. Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial. Nat Med. 2026 Jan 28. doi: 10.1038/s41591-025-04189-2. Online ahead of print.

  PMID: 41606119 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Gianluca Ianiro, MD

  Fondazione Policlinico Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: To mask treatments to physicisans and recipients, both FMT bottles and syringes will be covered with dark-coloured paper before the infusion, and the patients will be unable to see the endoscopic display during the procedure. Moreover, the physicians who will evsaluate patients at follow-up will not aware of the treatment being administered.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Model Details: randomized controlled trial

Study Record Dates

• First Submitted: February 11, 2021
• First Posted: February 17, 2021
• Study Start: February 18, 2021
• Primary Completion: December 16, 2024
• Study Completion: July 28, 2025
• Last Updated: September 8, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: data will be available after the completion of the study, for 5 years
• Access Criteria: Data will be given upon request to the PI

Locations

IT (2)