NCT06643533

Fecal Microbiota Transplantation in Reversing Drug Resistance in Unresectable HCC (TALENP004)

Safety and Efficacy of Fecal Microbiota Transplantation in Reversing Drug Resistance in Patients With Intermediate-advanced Unresectable Hepatocellular Carcinoma Undergoing Transcatheter Arterial Chemoembolization Combined With Lenvatinib Plus Sintilimab.

• Status: Not Yet Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 15 (estimated)
• Sponsor: Fujian Provincial Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This study aims to evaluate the safety and efficacy of fecal microbiota transplantation (FMT) in reversing drug resistance to the triple therapy regimen in patients with unresectable hepatocellular carcinoma (HCC). The triple therapy consists of transarterial chemoembolization (TACE), lenvatinib, and Sintilimab. The study is a prospective, single-arm, multicenter clinical trial involving 15 participants with mid-to-late stage HCC that has progressed despite the triple therapy. FMT capsules will be prepared by matching the gut microbiome profiles of healthy donors to those of patients who achieved complete response (CR) with the triple therapy. The primary endpoints include objective response rate (ORR), treatment-related adverse events (AEs). Secondary endpoints will assess overall survival (OS), progression-free survival (PFS), and disease control rate (DCR), changes in gut microbiome, metabolomics, and immune subsets before and after FMT.

Detailed description

The study is designed to investigate the potential of FMT in overcoming resistance to a combined treatment approach for HCC. The triple therapy under investigation includes TACE, lenvatinib, and a PD-1 inhibitor, which has shown promise in treating HCC but has encountered issues with drug resistance. This prospective, single-arm, multicenter trial will enroll 15 patients diagnosed with mid-to-late stage HCC that has progressed despite treatment with the triple therapy. The primary objective is to assess the safety and efficacy of FMT in this patient population, with the primary endpoints being ORR, AEs, OS, PFS, and DCR. Secondary endpoints will evaluate the changes in the gut microbiome composition, metabolomic profiles, and immune cell subsets before and after FMT. Eligible participants must have HCC that has progressed following the triple therapy and meet specific inclusion criteria, including having at least one measurable lesion, an expected survival time greater than three months, and no prior FMT treatment. Exclusion criteria include a history of other malignancies within the past five years, autoimmune diseases, and the use of immunosuppressive agents. FMT capsules will be made by analyzing the gut microbiome and metabolite profiles of patients who achieved a complete response to the triple therapy, and matching these with healthy donor profiles from a biobank. Patients will receive FMT capsules daily for three days, along with the continuation of the triple therapy. The study will also include procedures for dose adjustments based on adverse events and specific guidelines for managing toxicities related to the study treatments. The study will conclude with a comprehensive analysis of the primary and secondary endpoints. This trial aims to provide valuable insights into the role of FMT in enhancing the efficacy of cancer treatments and overcoming drug resistance in HCC.

Conditions

• Hepatocellular Carcinoma Non-resectable

Interventions

Type	Name	Description
OTHER	Fecal Microbiota Transplantation	The FMT capsules will be prepared by matching the gut microbiome profiles of healthy donors with those of patients who achieved a complete response to the triple therapy. The FMT capsules will be taken orally at a dosage of 30 capsules per day for the first 3 days of each treatment cycle. The FMT intervention will be administered in 6 cycles, with each cycle lasting for 21 days (Q3W). The duration of the treatment will be determined by the response to therapy, with a maximum of 6 cycles or until disease progression, intolerable toxicity, or participant withdrawal of consent. The FMT capsules are intended to modify the gut microbiome to reverse the resistance to the triple therapy and enhance the therapeutic response.

Timeline

• Start date: 2025-01-01
• Primary completion: 2027-06-01
• Completion: 2027-12-31
• First posted: 2024-10-16
• Last updated: 2024-10-16