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Signs and Symptoms, Digestive

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Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

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Amino Acids

Tyrosine Kinase Inhibitors

Tyrosine

Fecal microbiota transplantation using stools from healthy donors

Donor FMT

Sham FMT

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.

Despite the improvement in diagnosis and management, renal cell carcinoma (RCC) remains one of the most burdensome urological cancers, being the sixth most common malignancy in men and the 10th in women, accounting, respectively, for 5% and 3% of all cancers. Moreover, the incidence of RCC is increasing, especially in Western countries, accounting for nearly 60000 new cases per year in the United States. A considerable proportion of patients present with metastatic disease at diagnosis, and there are more than 140000 RCC-dependent deaths per year worldwide according to the World Health Organization.

Sunitinib and pazopanib are oral multi-targeted receptor tyrosine kinase inhibitors (TKIs) that have dramatically improved the survival of patients with metastatic RCC, and are commonly used as first-line option for this condition.

However, long-term use of these drugs is prevented by the development of toxicity. Diarrhea is one of the most common side effects of TKIs, occurring in nearly 50% of patients. It decreases the quality of life of these patients, and often requires dose reduction and drug discontinuation, potentially decreasing the efficacy of TKIs.

To date there are no standardized strategies for TKIs-related diarrhea, and current recommendations are supported by few evidence or real-life experience. Recommended treatment options include anti-motility agents, which are not targeted to act on the pathogenic pathways of diarrhea.

Increasing evidence suggests that gut microbiota could influence the development of TKIs-induced diarrhea. Overall, chemotherapy is known to drive, through the development of mucositis, deep compositional and functional alterations of gut microbiota. Mucositis occurs commonly after treatment with TKIs, and a specific dysbiotic profile has been found in patients with TKIs-induced diarrhea.

In theory, the therapeutic modulation of gut microbiota could be an approach to alleviate TKI-induced diarrhea. Although probiotics have been suggested as a possible treatment option for this condition, few evidence supports this indication.

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.

FMT has been also examined as a potential approach for other disorders associated with a disruption of gut microbiota, including ulcerative colitis or metabolic syndrome.

To date, the effects of FMT on chemotherapy-related diarrhea are unknown. The aim of this study is to investigate the efficacy of fecal microbiota transplantation (FMT), compared with sham FMT, in treating TKI-induced diarrhea in patients with metastatic RCC

Fecal Microbiota Transplantation in Diarrhea Induced by Tyrosine-kinase Inhibitors

Fecal Microbiota Transplantation to Treat Diarrhea Induced by Tyrosine-kinase Inhibitors in Patients With Metastatic Renal Cell Carcinoma: a Randomized Clinical Trial.

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

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

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

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

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

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

rate of patients who experience decrease of diarrhea until grade G1 or lower 2 weeks after the end of treatments

rate of patients who experience decrease of diarrhea until grade G1 or lower 4 weeks after the end of treatments

rate of patients who experience decrease of diarrhea until grade G1 or lower 8 weeks after the end of treatments

Catholic University of the Sacred Heart

Professor

Antineoplastic Agents

Pharmaceutical Solutions

Immune Checkpoint Inhibitors

Patients enrolled in this arm will receive donor FMT

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

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

donor FMT

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

Placebo FMT

Gianluca Ianiro, MD

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.

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 18 months and the follow up period will be 12 months and the median survival is 15.1 months. The total number of events will be 35. Microbiome analysis will be performed with shotgun sequencing techniques.

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.

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

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

Individual participant data will be available to other researchers

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

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

The investigators will evaluate the number of participants who will die for any reason throughout the study period (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)

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Fecal Microbiota Transplantation in Diarrhea Induced by Tyrosine-kinase Inhibitors	NCT04040712	Diarrhea Caused... Renal Cell Canc...	Donor FMT Sham FMT	18 Years -	Catholic University of the Sacred Heart
Fecal Microbiota Transplantation to Improve Efficacy of Immune Checkpoint Inhibitors in Renal Cell Carcinoma	NCT04758507	Renal Cell Carc...	donor FMT Placebo FMT	18 Years - 80 Years	Fondazione Policlinico Universitario Agostino Gemelli IRCCS

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Spots Global Cancer Trial Database for donor fmt

Every month we try and update this database with for donor fmt cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for donor fmt cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.