NCT04758507

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

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 50 (actual)
• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Renal Cell Carcinoma

Interventions

Type	Name	Description
BIOLOGICAL	donor FMT	This intervention is represented by the administration, in the recipients' gut, of donor microbiota through FMT
OTHER	Placebo FMT	This intervention is represented by the administration, in the recipients' gut, of a placebo through FMT

Timeline

• Start date: 2021-02-18
• Primary completion: 2024-12-16
• Completion: 2025-07-28
• First posted: 2021-02-17
• Last updated: 2025-09-08

Locations

2 sites across 1 country: Italy