Single Arm Clinical Trial (Gut Microbiota and HCC)

A Clinical Study to Evaluate the Effectiveness of Oral Enterobacterial Capsules in Patients With Intermediate and Advanced HCC Who Have Progressed After Immune Checkpoint Inhibitor Combination With Anti-Angiogenesis Targeted Agents

To evaluate the efficacy and safety of oral enterobacterial capsules in patients with intermediate and advanced HCC who have progressed after treating with immune checkpoint inhibitors in combination with anti-angiogenesis targeted agents.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Cancer
• Intervention / Treatment: Biological: Oral enterobacterium capsules

Detailed Description

This is a prospective, single-center, single-arm clinical study. For those who meet the enrollment conditions, the original regimen of immune checkpoint inhibitors combined with anti-angiogenic targeted drugs will remain unchanged after enrollment.On this basis, the study subjects started oral enterobacterial capsules to see whther enterobacterial capsules could improve the efficacy of patients receiving the above treatment regimens.

Oral administration of intestinal bacteria capsules 6 capsules/day, after observing no adverse reactions, oral administration for 10 consecutive days, 6 capsules/day from the second day to the tenth day, and then discontinued to the next course of treatment.

Total course of treatment: a total of 4 courses of oral intestinal bacteria capsules, each course of oral administration for 10 days, and a course of 21 days; A course of TKI combined with immune checkpoint inhibitors treatment is 21 days until the disease progresses or intolerable toxicity and side effects appear.

Observe the metrics: Primary Clinical Endpoint - Progression-Free Survival (PFS); Secondary Clinical Endpoints - Overall Growth Phase (OS), Objective Response Rate (ORR), Duration of Response (DOR), and Disease Control Rate (DCR). The new RECIST1.1 criteria were used for the efficacy evaluation system, the CTCAE5.0 grading system was used for the evaluation of common adverse reactions during treatment, and other indicators included imaging including conventional biochemical indexes such as CT and ultrasound, as well as quality of life scores.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dongmei Gou, Dr; Phone Number: 13696020717; Email: gdm4726@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-75 years old, gender is not limited;
2. Confirmed imaging or histological diagnosis of unresectable HCC, BCLC stadium B or C;
3. Clinical diagnosis of HCC progression during TKIs combined with ICIs treatment;
4. Not suitable for local ablation or chemoembolization;
5. Child-Pugh Grade A;
6. ≥ 1 measurable lesion (RECIST v1.1)
7. ECOG PS 0-1

Exclusion Criteria:

1. Usage of antibiotics within 2 weeks prior enrollment;
2. Diagnosis of immunodeficiency (e.g. HIV, immunosuppressants)
3. Patients with known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
4. Female patients who are pregnant or breastfeeding;
5. Patients with untreated acute or chronic active hepatitis B or hepatitis C infection.
6. Patients are currently undergoing clinical trials of other drugs;
7. Patients are considered by the investigator to be unsuitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with progressed HCC after treatment were given enterobacterium capsules; Patients were given oral enterobacterium capsules (300 mg/per capsule) 6 capsules/day for 10 consecutive days, and then discontinued to the next course of treatment.	Biological: Oral enterobacterium capsules; Enterobacterium capsules (300 mg/per capsule) orally 6 capsules/day for 10 consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Progression-Free Survival (PFS)	To analyse the Progression-Free Survival (PFS) of patients	Up to approximately 1 years
Objective Secondary Clinical Endpoints - Overall Growth Phase (OS)	To analyse the Secondary Clinical Endpoints - Overall Growth Phase (OS) of patients	Up to approximately 1 years
Objective Objective Response Rate (ORR)	To exprole the Objective Response Rate (ORR) of patients	Up to approximately 1 years
ObjectiveDuration of Response (DOR)	To analyse the Duration of Response (DOR) of patients	Up to approximately 1 years
Diversity analysis	We will use 16S rRNA sequencing to measure fecal sample. The alpha and beta diversity of gut microbiota will be analyzed, including a series of statistical analysis indexes such as Chao, Shannon, Simpsonace, Simpson and Coverage, in order to reflect the microbial community diversity.	Up to approximately 1 years
Species differential analysis	We will use 16S rRNA sequencing to measure fecal sample. Based on the results of species annotation, the PCA、PCoA and NMDS analysis will be used to assess the similarities and differences in species composition.	Up to approximately 1 years
Feces Metabolomics	Changes of metabolites in feces measured by metabolomic mass spectrometry, unsupervised PCA (principal component analysis) was performed by statistics function prcomp, identified metabolites were annotated using KEGG Compound database.	Up to approximately 1 years
Serum Metabolomics	Changes of metabolites in serum measured by metabolomic mass spectrometry, unsupervised PCA (principal component analysis) was performed by statistics function prcomp, identified metabolites were annotated using KEGG Compound database.	Up to approximately 1 years

Collaborators and Investigators

• Sponsor: Xu Yong, MD
• Collaborators: Nanjing Xiershou Biotechnology Co., Ltd
• Investigators: Principal Investigator: Yong Xu, Dr, Secretary of the Party Committee of the Shenzhen Third People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 24, 2024
• Primary Completion (Estimated): May 20, 2026
• Study Completion (Estimated): November 20, 2026

Study Registration Dates

• First Submitted: August 14, 2024
• First Submitted That Met QC Criteria: August 18, 2024
• First Posted (Actual): August 21, 2024

Study Record Updates

• Last Update Posted (Actual): August 21, 2024
• Last Update Submitted That Met QC Criteria: August 18, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms
• Other Study ID Numbers: KY2024-178

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No