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

NCT06563934 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: KY2024-177
• Study Type: interventional
• Target: 70
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Liver Cancer

Outcome Measures

Primary Outcomes (8)

• 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

Study Arms (2)

Experimental: Lenvatinib + PD-1 monoclonal antibody + Enterobacterium capsules

EXPERIMENTAL

1. 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. 2. 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; Drug: Lenvatinib + PD-1 monoclonal antibody

Lenvatinib + PD-1 monoclonal antibody + Enterobacterium capsules placebo

PLACEBO COMPARATOR

1. 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. 2. 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; Biological: Oral enterobacterium capsules placebo

Interventions

Oral enterobacterium capsules BIOLOGICAL

Enterobacterium capsules (300 mg/per capsule) orally 6 capsules/day for 10 consecutive days.

Experimental: Lenvatinib + PD-1 monoclonal antibody + Enterobacterium capsules

Lenvatinib + PD-1 monoclonal antibody DRUG

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.

Experimental: Lenvatinib + PD-1 monoclonal antibody + Enterobacterium capsules; Lenvatinib + PD-1 monoclonal antibody + Enterobacterium capsules placebo

Oral enterobacterium capsules placebo BIOLOGICAL

Enterobacterium capsules placebo (300 mg/per capsule) orally 6 capsules/day for 10 consecutive days.

Lenvatinib + PD-1 monoclonal antibody + Enterobacterium capsules placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years old, gender is not limited;
• Confirmed imaging or histological diagnosis of unresectable HCC, BCLC stadium B or C;
• Previous treatment without systemic therapy;
• Intended to be treated with anti-angiogenic targeted drugs combined with immune checkpoint inhibitors;
• Child-Pugh Grade A;
• ≥ 1 measurable lesion (RECIST v1.1)
• ECOG PS 0-1

You may not qualify if:

• Usage of antibiotics within 2 weeks prior enrollment;
• Diagnosis of immunodeficiency (e.g. HIV, immunosuppressants)
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
• Female patients who are pregnant or breastfeeding;
• Patients with untreated acute or chronic active hepatitis B or hepatitis C infection.
• Those who are currently undergoing clinical trials of other drugs;

Sponsors & Collaborators

• Xu Yong, MD: lead
• Nanjing Xiershou Biotechnology Co., Ltd: collaborator

MeSH Terms

Conditions

Liver Neoplasms

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Study Officials

• Yong Xu, Dr

  Secretary of the Party Committee of the Shenzhen Third People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dongmei Gou, Dr

CONTACT

13696020717; gdm4726@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a prospective, single-center, randomized, double-blind controlled trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Secretary of the Party Committee

Model Details: 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.

Study Record Dates

• First Submitted: August 13, 2024
• First Posted: August 21, 2024
• Study Start: August 30, 2024
• Primary Completion: May 20, 2026
• Study Completion (Estimated): November 20, 2026
• Last Updated: August 21, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share