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

NCT ID: NCT06563934

Last Updated: 2024-08-21

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-30
• Study Completion Date: 2026-11-20

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.

Conditions

Liver Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Oral enterobacterium capsules

Intervention Type: BIOLOGICAL

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

Lenvatinib + PD-1 monoclonal antibody

Intervention Type: 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.

Lenvatinib + PD-1 monoclonal antibody + Enterobacterium capsules placebo

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.

Group Type: PLACEBO_COMPARATOR

Lenvatinib + PD-1 monoclonal antibody

Intervention Type: 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.

Oral enterobacterium capsules placebo

Intervention Type: BIOLOGICAL

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

Interventions

Oral enterobacterium capsules

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

Intervention Type: BIOLOGICAL

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.

Intervention Type: DRUG

Oral enterobacterium capsules placebo

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

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nanjing Xiershou Biotechnology Co., Ltd

UNKNOWN

Sponsor Role: collaborator

Xu Yong, MD

OTHER

Sponsor Role: lead

Responsible Party

Xu Yong, MD

Secretary of the Party Committee

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Yong Xu, Dr

Role: PRINCIPAL_INVESTIGATOR

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

Central Contacts

Dongmei Gou, Dr

Role: CONTACT

gdm4726@163.com

13696020717

Other Identifiers

KY2024-177

Identifier Type: -

Identifier Source: org_study_id