Fecal Microbiota Transplantation in Diarrhea Induced by Tyrosine-kinase Inhibitors

NCT04040712 | Completed

• 1 other identifier: FMT-TKI-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with metastatic renal cell carcinoma, and are commonly used as first-line option for this condition, but their use is encumbered by side effects, mainly diarrhea, for which there are no standardized strategies. Increasing evidence suggests that gut microbiota could influence the development of TKIs-induced diarrhea. In theory, the therapeutic modulation of gut microbiota could be an approach to alleviate TKI-induced diarrhea. Fecal microbiota transplantation (FMT) is the infusion of fecal microbiota from a healthy donor in the gut of a recipient with the aim of curing a specific disease. It has been increasingly recognized as a highly effective treatment against recurrent Clostridium difficile infection.To date, the effects of FMT on chemotherapy-related diarrhea are unknown. This study will evaluate, through a randomized controlled design, the efficacy of fecal microbiota transplantation (FMT), compared with sham FMT, in treating TKI-induced diarrhea in patients with metastatic renal cell carcinoma.

Conditions

Diarrhea Caused by Drug (Disorder); Renal Cell Cancer

Keywords

fecal microbiota transplantation; microbiota; chemotherapy; diarrhea; renal cell carcinoma

Outcome Measures

Primary Outcomes (1)

• rate of patients who experience resolution of diarrhea 4 weeks after the end of treatments

  rate of patients who experience resolution of diarrhea 4 weeks after the end of treatments

  4 weeks

Secondary Outcomes (8)

• rate of patients who need to stop or reduce treatment with tyrosine-kinase inhibitors

  4 weeks

• rate of patients who experience resolution of diarrhea 1 week after the end of treatments

  1 week

• rate of patients who experience resolution of diarrhea 2 weeks after the end of treatments

  2 weeks

• rate of patients who experience resolution of diarrhea 8 weeks after the end of treatments

  8 weeks

• rate of patients who experience decrease of diarrhea until grade G1 or lower 1 week after the end of treatments

  1 week

Study Arms (2)

Donor FMT

EXPERIMENTAL

Fecal microbiota transplantation using stools from healthy donors

Other: Donor FMT

Sham FMT

SHAM COMPARATOR

Sham fecal microbiota transplantation

Other: Sham FMT

Interventions

Donor FMT OTHER

Fecal microbiota transplantation using stools from healthy donors

Donor FMT

Sham FMT OTHER

Sham fecal microbiota transplantation

Sham FMT

Eligibility Criteria

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

You may qualify if:

• years old or older
• treatment with pazopanib or sunitinib for metastatic RCC diagnosed at histology and measurable according to RECIST criteria version 1.1
• development of diarrhea of 2-3 grade according to Common Terminology Criteria (CTC) for Adverse Events (AE) version 4.0 induced by these drugs.
• execution of a CT scan no earlier than 4 weeks before enrollment
• good or intermediate prognostic assessment (according to criteria of the prognostic system of the International Metastatic RCC Database Consortium)
• performance status equal or lower than 2
• blood count, hepatic and kidney testing within normal limit
• ability to give their consent to be included in the study.

You may not qualify if:

• another known cause of diarrhea (e.g. infectious gastroenteritis. Clostridium difficile infection, celiac disease, inflammatory bowel disease, irritable bowel syndrome, chronic pancreatitis, biliary salt diarrhea)
• previous colorectal surgery or cutaneous stoma
• food allergies
• recent (\<6 weeks) therapy with drugs that could possibly alter gut microbiota (e.g. antibiotics, probiotics, proton pump inhibitors, immunosuppressants, metformin)
• another cancer (except for surgically treated basocellular carcinoma)
• brain metastases
• decompensated heart failure or heart disease with ejection fraction lower than 30%
• severe respiratory insufficiency
• psychiatric disorders
• pregnancy
• unable to give informed consent.

Sponsors & Collaborators

• Catholic University of the Sacred Heart: lead

Study Sites (1)

Fondazione Policlinico Universitario "A. Gemelli" IRCCS

Rome, 00168, Italy

Location

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Diarrhea

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; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 22, 2019
• First Posted: August 1, 2019
• Study Start: August 2, 2019
• Primary Completion: January 5, 2020
• Study Completion: February 5, 2020
• Last Updated: March 17, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)