Gut Microbiota in Liver Cancer (Treated With TKIs In Combination With ICIs)

A Randomized Controlled Trial Evaluating the Effects of Oral Enterobacterial Capsules in Liver Cancer Patients Treated With Tyrosine Kinase Inhibitors (TKIs) in Combination With Immune Checkpoint Inhibitors (ICIs)

To evaluate the additional efficacy and safety of oral enterobacterial capsules in patients with intermediate and advanced liver cancer and treated with tyrosine kinase inhibitors (TKIs) combined with immunotherapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Cancer
• Intervention / Treatment: Biological: Oral enterobacterium capsules; Drug: Lenvatinib + PD-1 monoclonal antibody; Biological: Oral enterobacterium capsules placebo

Detailed Description

This is a prospective, single-center, randomized, double-blind controlled trial. The clinical study is divided into 2 groups:

Group 1) Patients in the control group were given lenvatinib 8mg (≤ 60 kg body weight) or 12 mg (> 60 kg body weight) orally once a day, combined with PD-1 monoclonal antibody 200mg intravenously once every 3 weeks until disease progression, intolerable toxicity or death, and patients in the control group were given intestinal bacteria capsules placebo.

Group 2) Patients in the study group were given lenvatinib 8 mg (≤ 60 kg body weight) or 12 mg (> 60 kg body weight) orally once a day in combination with PD-1 monoclonal antibody 200 mg intravenously every 3 weeks until disease progression, intolerable toxicity, or death, and patients in this study group were given intestinal bacteria capsules.

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): 70
• 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. Previous treatment without systemic therapy;
4. Intended to be treated with anti-angiogenic targeted drugs combined with immune checkpoint inhibitors;
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. 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. Those who are currently undergoing clinical trials of other drugs;
7. Other patients who are considered by the investigator to be unsuitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Lenvatinib + PD-1 monoclonal antibody + Enterobacterium capsules; Lenvatinib 8mg (≤60 kg body weight) or 12 mg (> 60 kg body weight) orally once a day. PD-1 monoclonal antibody 200mg i.v. once every 3 weeks.; Enterobacterium capsules (300 mg/per capsule) orally 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.; Drug: Lenvatinib + PD-1 monoclonal antibody; Lenvatinib 8mg (≤60 kg body weight) or 12 mg (> 60 kg body weight) orally once a day. PD-1 monoclonal antibody 200mg i.v. once every 3 weeks.
Placebo Comparator: Lenvatinib + PD-1 monoclonal antibody + Enterobacterium capsules placebo; Lenvatinib 8mg (≤60 kg body weight) or 12 mg (> 60 kg body weight) orally once a day. PD-1 monoclonal antibody 200mg i.v. once every 3 weeks.; Enterobacterium capsules placebo (300 mg/per capsule) orally 6 capsules/day for 10 consecutive days, and then discontinued to the next course of treatment.	Drug: Lenvatinib + PD-1 monoclonal antibody; Lenvatinib 8mg (≤60 kg body weight) or 12 mg (> 60 kg body weight) orally once a day. PD-1 monoclonal antibody 200mg i.v. once every 3 weeks.; Biological: Oral enterobacterium capsules placebo; Enterobacterium capsules placebo (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 30, 2024
• Primary Completion (Estimated): May 20, 2026
• Study Completion (Estimated): November 20, 2026

Study Registration Dates

• First Submitted: August 13, 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Protein Kinase Inhibitors; Antibodies; Antibodies, Monoclonal; Lenvatinib
• Other Study ID Numbers: KY2024-177

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