Advanced Hepatocellular Carcinoma
Conditions
Brief summary
This prospective, single-center, single-arm phase 2 study evaluates the efficacy and safety of adding oral fecal microbiota transplantation (FMT) capsules to continued immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) therapy in adults with advanced hepatocellular carcinoma (HCC) whose disease has progressed during ICI-TKI therapy.
Detailed description
This is a prospective, single-center, single-arm clinical study evaluating the efficacy and safety of oral fecal microbiota transplantation (FMT) capsules in patients with advanced hepatocellular carcinoma (HCC) whose disease has progressed during immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) therapy. After enrollment, participants will continue the same ICI-TKI regimen according to its prescribed schedule. In addition, oral FMT capsules (300 mg per capsule) will be administered at 6 capsules per day for 10 consecutive days in each 21-day cycle, for a total of 4 cycles. ICI-TKI therapy will continue until disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion. The primary endpoint is progression-free survival (PFS), defined as the time from the first dose of FMT capsules to the first documented radiographic disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first. Secondary endpoints include overall survival (OS), defined as the time from the first dose of FMT capsules to death from any cause; objective response rate (ORR), defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) according to RECIST version 1.1; duration of response (DOR), defined for participants with CR or PR as the time from the first documented response to radiographic disease progression or death from any cause, whichever occurs first; and disease control rate (DCR), defined as the proportion of participants with CR, PR, or stable disease (SD) according to RECIST version 1.1. Adverse events will be evaluated and graded according to CTCAE version 5.0. Other assessments include protocol-specified imaging, laboratory tests, and quality-of-life measures.
Interventions
BIOLOGICALOral fecal microbiota transplantation capsules
Oral fecal microbiota transplantation capsules (300 mg per capsule) are administered at a dose of 6 capsules per day for 10 consecutive days in each 21-day cycle, for a total of 4 cycles. Participants continue their pre-enrollment ICI-TKI regimen during FMT treatment.
Sponsors
Xu Yong, MD
Nanjing Xiershou Biotechnology Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a prospective, single-center, open-label, single-arm phase 2 study. Participants continue their pre-enrollment ICI-TKI regimen and receive oral fecal microbiota transplantation (FMT) capsules at 6 capsules per day for 10 consecutive days in each 21-day cycle, for a total of 4 cycles.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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. Clinical diagnosis of HCC progression during TKIs combined with ICIs treatment; 4. Not suitable for local ablation or chemoembolization; 5. Child-Pugh class A or B, with a score of ≤7; 6. ≥ 1 measurable lesion (RECIST v1.1) 7. ECOG PS 0-2
Exclusion criteria
1. Use of antibiotics within 4 weeks prior enrollment; 2. Diagnosis of immunodeficiency (e.g. HIV, immunosuppressants) 3. Patients with 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. Patients are currently undergoing clinical trials of other drugs; 7. Patients are considered by the investigator to be unsuitable for inclusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From the first dose of FMT capsules to radiographic disease progression or death, up to approximately 1 year | Time from the first dose of FMT capsules to the first documented radiographic disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From the first dose of FMT capsules to death from any cause, up to approximately 1 year | Time from the first dose of FMT capsules to death from any cause. |
| Objective Response Rate (ORR) | From the first dose of FMT capsules through approximately 1 year | Proportion of participants with a best overall response of complete response or partial response according to RECIST version 1.1. |
| Duration of Response (DOR) | From the first documented response to disease progression or death, up to approximately 1 year | For participants with a complete or partial response, time from the first documented response to radiographic disease progression or death from any cause, whichever occurs first. |
| Disease Control Rate (DCR) | From the first dose of FMT capsules through approximately 1 year | Proportion of participants with a best overall response of complete response, partial response, or stable disease according to RECIST version 1.1. |
Countries
China
Contacts
CONTACTCineng Xu, Dr
PRINCIPAL_INVESTIGATORYong Xu, Dr
Secretary of the Party Committee of the Shenzhen Third People's Hospital
Outcome results
None listed