Clinical trial NCT06563934: Gut Microbiota in Liver Cancer (Treated With TKIs In Combination With ICIs)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Liver Cancer
Lead sponsor: Shenzhen Third People's Hospital
Sponsor class: OTHER
Collaborators: name: Nanjing Xiershou Biotechnology Co., Ltd
First posted: 2024-08-21
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Progression-Free Survival (PFS)
timeFrame: Up to approximately 1 years
measure: Objective Secondary Clinical Endpoints - Overall Growth Phase (OS)
timeFrame: Up to approximately 1 years
measure: Objective Objective Response Rate (ORR)
timeFrame: Up to approximately 1 years
measure: ObjectiveDuration of Response (DOR)
timeFrame: Up to approximately 1 years
measure: Diversity analysis
timeFrame: Up to approximately 1 years
measure: Species differential analysis
timeFrame: Up to approximately 1 years
measure: Feces Metabolomics
timeFrame: Up to approximately 1 years
measure: Serum Metabolomics
timeFrame: Up to approximately 1 years
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Secretary of the Party Committee of the Shenzhen Third People's Hospital
name: Yong Xu, Dr
role: PRINCIPAL_INVESTIGATOR
References: