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)
Trial Snapshot
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 70
- Primary Endpoint
- ObjectiveDuration of Response (DOR)
Study Overview
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.
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Masking Description
This is a prospective, single-center, randomized, double-blind controlled trial.
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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;
- •Other patients who are considered by the investigator to be unsuitable for inclusion.
Arms & Interventions
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.
Intervention: Oral enterobacterium capsules (Biological)
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.
Intervention: Lenvatinib + PD-1 monoclonal antibody (Drug)
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.
Intervention: Lenvatinib + PD-1 monoclonal antibody (Drug)
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.
Intervention: Oral enterobacterium capsules placebo (Biological)
Outcomes
Primary Outcomes
ObjectiveDuration of Response (DOR)
Time Frame: Up to approximately 1 years
To analyse the Duration of Response (DOR) of patients
Objective Secondary Clinical Endpoints - Overall Growth Phase (OS)
Time Frame: Up to approximately 1 years
To analyse the Secondary Clinical Endpoints - Overall Growth Phase (OS) of patients
Objective Objective Response Rate (ORR)
Time Frame: Up to approximately 1 years
To exprole the Objective Response Rate (ORR) of patients
Species differential analysis
Time Frame: Up to approximately 1 years
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.
Feces Metabolomics
Time Frame: Up to approximately 1 years
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.
Objective Progression-Free Survival (PFS)
Time Frame: Up to approximately 1 years
To analyse the Progression-Free Survival (PFS) of patients
Diversity analysis
Time Frame: Up to approximately 1 years
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.
Serum Metabolomics
Time Frame: Up to approximately 1 years
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.
Secondary Outcomes
No secondary outcomes reported
Investigators
Xu Yong, MD
Secretary of the Party Committee
Shenzhen Third People's Hospital