Hepatocellular Carcinoma Non-resectableNCT06643533
Fecal Microbiota Transplantation in Reversing Drug Resistance in Unresectable HCC (TALENP004)
An observational study of Hepatocellular Carcinoma Non-resectable, run by Fujian Provincial Hospital.
Trial summary
This study aims to evaluate the safety and efficacy of fecal microbiota transplantation (FMT) in reversing drug resistance to the triple therapy regimen in patients with unresectable hepatocellular carcinoma (HCC). The triple therapy consists of transarterial chemoembolization (TACE), lenvatinib, and Sintilimab. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma Non-resectable
- What is being tested?
- Fecal Microbiota Transplantation
- Type of treatment
- Pill or oral medicine
- How many people
- 15 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2025to 31 Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population consists of adults aged 18 to 75 with unresectable hepatocellular carcinoma that has progressed after triple therapy, eligible for fecal microbiota transplantation to overcome treatment resistance.
Who may be able to join
- Patients with intermediate to advanced Hepatocellular Carcinoma (HCC) who have experienced disease progression (PD) after treatment with the triple therapy of Transarterial Chemoembolization (TACE), lenvatinib, and sintilimab.
- Patients must have at least one measurable lesion according to the mRECIST 1.1 criteria (the longest diameter of measurable lesions on CT/MRI scan ≥10mm).
- Expected survival time greater than 3 months.
- No prior treatment with Fecal Microbiota Transplantation (FMT).
- No history of taking probiotics after the diagnosis of HCC.
- Child-Pugh class A/B.
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- ECOG performance status: ≤1.
- Age between 18 and 75 years old.
- No other antitumor treatments except the triple therapy before enrollment.
- Key organ function indicators meet the following requirements:
- Hematology: Absolute neutrophil count ≥1.5×10^9/L, Hb ≥9.0g/L, Platelets ≥75×10^9/L Liver function: Total bilirubin ≤1.5 times the upper limit of normal (ULN) (≤2.5 times ULN after biliary drainage for obstructive jaundice); Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) ≤5 times ULN, Albumin ≥30g/L Renal function: Serum creatinine ≤1.5mg/dL, Creatinine clearance rate ≥60ml/min Coagulation function: International normalized ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤1.5 times ULN
- No history of severe arrhythmias, heart failure, severe ventilatory dysfunction, or severe pulmonary infections.
- Women of childbearing age must agree to use contraceptive measures during the treatment period and for 6 months after the end of treatment, with a negative serum or urine pregnancy test within 7 days before study enrollment, and must not be breastfeeding. Men must agree to use contraceptive measures during the study period and for 6 months after the end of the study.
Who cannot join
- Mixed hepatocellular-cholangiocarcinoma.
- Severe tumor progression (tumor volume occupies two-thirds or more of the liver volume or diffuse intrahepatic lesions).
- History of allergy to PD-1, lenvatinib, or their components.
- History of other malignant tumors within the past 5 years, except for cured basal cell carcinoma of the skin, cervical carcinoma in situ, and papillary thyroid cancer.
- Patients who have undergone organ transplantation or are planning to undergo organ transplantation.
- Any active autoimmune disease or autoimmune disease with expected recurrence (such as interstitial pneumonia, colitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases and syndromes).
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- History of immunodeficiency; patients who are using immunosuppressants or systemic corticosteroid therapy for immunosuppression and have continued use within 2 weeks before signing the informed consent.
- Known hereditary or acquired bleeding (such as coagulation disorders) or thrombotic tendencies, such as hemophilia patients; currently using or have recently (within 10 days before the start of the study treatment) used full-dose oral or injectable anticoagulants or thrombolytic drugs for therapeutic purposes (preventive use of low-dose aspirin, low molecular weight heparin is allowed).
- Serious infections within 4 weeks before enrollment, such as severe pneumonia requiring hospitalization, bacteremia, infectious complications, etc.; baseline chest imaging indicates active pulmonary inflammation, presence of infection symptoms and signs or need for oral or intravenous antibiotic treatment within 2 weeks before the first use of the study drug (excluding the use of antibiotics for prevention).
- Patients with mental illness; history of abuse of psychotropic drugs, alcoholism, and drug addiction.
- Chronic intestinal diseases (such as celiac disease, malabsorption, etc.).
- Pregnant or breastfeeding women.
- Deemed by the investigator to be unsuitable for participation in this trial for other reasons.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Safety and Efficacy of Fecal Microbiota Transplantation in Reversing Drug Resistance in Patients With Intermediate-advanced Unresectable Hepatocellular Carcinoma Undergoing Transcatheter Arterial Chemoembolization Combined With Lenvatinib Plus Sintilimab.
This study aims to evaluate the safety and efficacy of fecal microbiota transplantation (FMT) in reversing drug resistance to the triple therapy regimen in patients with unresectable hepatocellular carcinoma (HCC). The triple therapy consists of transarterial chemoembolization (TACE), lenvatinib, and Sintilimab. The study is a prospective, single-arm, multicenter clinical trial involving 15 participants with mid-to-late stage HCC that has progressed despite the triple therapy. FMT capsules will be prepared by matching the gut microbiome profiles of healthy donors to those of patients who achieved complete response (CR) with the triple therapy. The primary endpoints include objective response rate (ORR), treatment-related adverse events (AEs). Secondary endpoints will assess overall survival (OS), progression-free survival (PFS), and disease control rate (DCR), changes in gut microbiome, metabolomics, and immune subsets before and after FMT.
Read the detailed description
The study is designed to investigate the potential of FMT in overcoming resistance to a combined treatment approach for HCC. The triple therapy under investigation includes TACE, lenvatinib, and a PD-1 inhibitor, which has shown promise in treating HCC but has encountered issues with drug resistance.
This prospective, single-arm, multicenter trial will enroll 15 patients diagnosed with mid-to-late stage HCC that has progressed despite treatment with the triple therapy. The primary objective is to assess the safety and efficacy of FMT in this patient population, with the primary endpoints being ORR, AEs, OS, PFS, and DCR. Secondary endpoints will evaluate the changes in the gut microbiome composition, metabolomic profiles, and immune cell subsets before and after FMT.
Eligible participants must have HCC that has progressed following the triple therapy and meet specific inclusion criteria, including having at least one measurable lesion, an expected survival time greater than three months, and no prior FMT treatment. Exclusion criteria include a history of other malignancies within the past five years, autoimmune diseases, and the use of immunosuppressive agents.
FMT capsules will be made by analyzing the gut microbiome and metabolite profiles of patients who achieved a complete response to the triple therapy, and matching these with healthy donor profiles from a biobank. Patients will receive FMT capsules daily for three days, along with the continuation of the triple therapy. The study will also include procedures for dose adjustments based on adverse events and specific guidelines for managing toxicities related to the study treatments.
The study will conclude with a comprehensive analysis of the primary and secondary endpoints. This trial aims to provide valuable insights into the role of FMT in enhancing the efficacy of cancer treatments and overcoming drug resistance in HCC.
- Conditions
- Hepatocellular Carcinoma Non-resectable
- Being tested
- Fecal Microbiota Transplantation
- Keywords
- Fecal Microbiota Transplantation, Hepatocellular Carcinoma, TACE, Lenvatinib, PD-1 inhibitor
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fecal Microbiota TransplantationOther
The FMT capsules will be prepared by matching the gut microbiome profiles of healthy donors with those of patients who achieved a complete response to the triple therapy. The FMT capsules will be taken orally at a dosage of 30 capsules per day for the first 3 days of each treatment cycle. The FMT intervention will be administered in 6 cycles, with each cycle lasting for 21 days (Q3W). The duration of the treatment will be determined by the response to therapy, with a maximum of 6 cycles or until disease progression, intolerable toxicity, or participant withdrawal of consent. The FMT capsules are intended to modify the gut microbiome to reverse the resistance to the triple therapy and enhance the therapeutic response.
| Study group | Role | What they receive |
|---|---|---|
| FMT-Resistant HCC Cohort | The triple therapy consists of:
Transarterial Chemoembolization (TACE): This procedure will be performed every 4-6 weeks based on the presence of significant arterial blood supply to the tumor, with a maximum of 4 TACE treatments allowed.
Lenvatinib: The generic name of the drug is lenvatinib. It will be administered orally in a dosage of 12mg per day for patients weighing 60kg or more, and 8mg per day for patients weighing less than 60kg. The treatment will be continuous with a fixed daily dosing schedule.
Sintilimab: It will be given every 3 weeks (Q3W). Fecal Microbiota Transplantation (FMT): The FMT capsules will be prepared by matching the gut microbiome profiles of healthy donors with those of patients who achieved a complete response to the triple therapy. The FMT capsules will be taken orally at a dosage of 30 capsules per day for the first 3 days of each treatment cycle.
The FMT intervention will be administered in 6 cycles, with each cycle lasting for 21 days (Q3W). Receives: Other: Fecal Microbiota Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate, ORR
The Objective response rate (ORR) was defined as the complete response (CR) rate or the partial response (PR) rate according to RECIST1.1.
Measured: Four weeks after the initiation of medication until the day before surgery
Adverse events
Grade 1-5 AEs according to NCI-CTCAE V5.0.
Measured: From the initiation of medication, with recordings made whenever an adverse reaction occurs, assessed up to 12 months
Secondary outcomes (6)
Overall survival, OS
The Overall survival (OS) was defined as the time between receiving treatment and observing death or loss of follow-up for any reason.
Measured: From date of enrollment until the date of death from any cause, assessed up to 60 months
Progression free survival, PFS
The Progression free survival (PFS) was defined as the time between the start of treatment and the progression of intrahepatic and/or extrahepatic tumors, or the occurrence of death or loss of follow-up for any reason.
Measured: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Disease control rate, DCR
The Disease control rate (DCR) was defined as the complete response (CR) rate or the partial response (PR) rate or stable disease (SD) rate according to RECIST1.1.
Measured: Four weeks after the initiation of medication until the day before surgery
Gut Microbiome Composition after Fecal Microbiota Transplantation
The changes in the gut microbiome composition before and after FMT treatment, including diversity and similarity to the donor microbiome.
Measured: Baseline and at the end of each treatment cycle (up to 6 cycles)
Gut Microbiome Metabolomic Changes after Fecal Microbiota Transplantation
The changes in serum and fecal metabolomics before and after FMT.
Measured: Baseline and at the end of each treatment cycle (up to 6 cycles)
Gut Microbiome Immune Subset Variations after Fecal Microbiota Transplantation
The changes in immune cell subsets before and after FMT.
Measured: Baseline and at the end of each treatment cycle (up to 6 cycles)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2024
- Study start1 Jan 2025 (estimated)
- Primary completion1 Jun 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma Non-resectableStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fujian Provincial Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mao-Lin Yan, Fujian Provincial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06643533
- Sponsor's protocol ID
- TALENP004
- Status last verified
- Oct 2024
- First submitted
- 11 Oct 2024
- Last updated
- 16 Oct 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Fecal Microbiota Transplantation in Reversing Drug Resistance in Patients With Intermediate-advanced Unresectable Hepatocellular Carcinoma Undergoing Transcatheter Arterial Chemoembolization Combined With Lenvatinib Plus Sintilimab.
- ClinicalTrials.gov ID
- NCT06643533
- Acronym / sponsor ID
- TALENP004
- Conditions
- Hepatocellular Carcinoma Non-resectable
- Keywords
- Fecal Microbiota Transplantation, Hepatocellular Carcinoma, TACE, Lenvatinib, PD-1 inhibitor
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Fujian Provincial HospitalUniversity, hospital or other
- Study start
- 1 Jan 2025 (estimated)
- Primary completion
- 1 Jun 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 16 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to evaluate the safety and efficacy of fecal microbiota transplantation (FMT) in reversing drug resistance to the triple therapy regimen in patients with unresectable hepatocellular carcinoma (HCC). The triple therapy consists of transarterial chemoembolization (TACE), lenvatinib, and Sintilimab. The study is a prospective, single-arm, multicenter clinical trial involving 15 participants with mid-to-late stage HCC that has progressed despite the triple therapy. FMT capsules will be prepared by matching the gut microbiome profiles of healthy donors to those of patients who achieved complete response (CR) with the triple therapy. The primary endpoints include objective response rate (ORR), treatment-related adverse events (AEs). Secondary endpoints will assess overall survival (OS), progression-free survival (PFS), and disease control rate (DCR), changes in gut microbiome, metabolomics, and immune subsets before and after FMT.
Detailed description
The study is designed to investigate the potential of FMT in overcoming resistance to a combined treatment approach for HCC. The triple therapy under investigation includes TACE, lenvatinib, and a PD-1 inhibitor, which has shown promise in treating HCC but has encountered issues with drug resistance.
This prospective, single-arm, multicenter trial will enroll 15 patients diagnosed with mid-to-late stage HCC that has progressed despite treatment with the triple therapy. The primary objective is to assess the safety and efficacy of FMT in this patient population, with the primary endpoints being ORR, AEs, OS, PFS, and DCR. Secondary endpoints will evaluate the changes in the gut microbiome composition, metabolomic profiles, and immune cell subsets before and after FMT.
Eligible participants must have HCC that has progressed following the triple therapy and meet specific inclusion criteria, including having at least one measurable lesion, an expected survival time greater than three months, and no prior FMT treatment. Exclusion criteria include a history of other malignancies within the past five years, autoimmune diseases, and the use of immunosuppressive agents.
FMT capsules will be made by analyzing the gut microbiome and metabolite profiles of patients who achieved a complete response to the triple therapy, and matching these with healthy donor profiles from a biobank. Patients will receive FMT capsules daily for three days, along with the continuation of the triple therapy. The study will also include procedures for dose adjustments based on adverse events and specific guidelines for managing toxicities related to the study treatments.
The study will conclude with a comprehensive analysis of the primary and secondary endpoints. This trial aims to provide valuable insights into the role of FMT in enhancing the efficacy of cancer treatments and overcoming drug resistance in HCC.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FMT-Resistant HCC Cohort | – | Other: Fecal Microbiota TransplantationThe triple therapy consists of: Transarterial Chemoembolization (TACE): This procedure will be performed every 4-6 weeks based on the presence of significant arterial blood supply to the tumor, with a maximum of 4 TACE treatments allowed. Lenvatinib: The generic name of the drug is lenvatinib. It will be administered orally in a dosage of 12mg per day for patients weighing 60kg or more, and 8mg per day for patients weighing less than 60kg. The treatment will be continuous with a fixed daily dosing schedule. Sintilimab: It will be given every 3 weeks (Q3W). Fecal Microbiota Transplantation (FMT): The FMT capsules will be prepared by matching the gut microbiome profiles of healthy donors with those of patients who achieved a complete response to the triple therapy. The FMT capsules will be taken orally at a dosage of 30 capsules per day for the first 3 days of each treatment cycle. The FMT intervention will be administered in 6 cycles, with each cycle lasting for 21 days (Q3W). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population consists of adults aged 18 to 75 with unresectable hepatocellular carcinoma that has progressed after triple therapy, eligible for fecal microbiota transplantation to overcome treatment resistance.
Key inclusion criteria (13 listed)
- Patients with intermediate to advanced Hepatocellular Carcinoma (HCC) who have experienced disease progression (PD) after treatment with the triple therapy of Transarterial Chemoembolization (TACE), lenvatinib, and sintilimab.
- Patients must have at least one measurable lesion according to the mRECIST 1.1 criteria (the longest diameter of measurable lesions on CT/MRI scan ≥10mm).
- Expected survival time greater than 3 months.
- No prior treatment with Fecal Microbiota Transplantation (FMT).
- No history of taking probiotics after the diagnosis of HCC.
Key exclusion criteria (13 listed)
- Mixed hepatocellular-cholangiocarcinoma.
- Severe tumor progression (tumor volume occupies two-thirds or more of the liver volume or diffuse intrahepatic lesions).
- History of allergy to PD-1, lenvatinib, or their components.
- History of other malignant tumors within the past 5 years, except for cured basal cell carcinoma of the skin, cervical carcinoma in situ, and papillary thyroid cancer.
- Patients who have undergone organ transplantation or are planning to undergo organ transplantation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fecal Microbiota TransplantationThe FMT capsules will be prepared by matching the gut microbiome profiles of healthy donors with those of patients who achieved a complete response to the triple therapy. The FMT capsules will be taken orally at a dosage of 30 capsules per day for the first 3 days of each treatment cycle. The FMT intervention will be administered in 6 cycles, with each cycle lasting for 21 days (Q3W). The duration of the treatment will be determined by the response to therapy, with a maximum of 6 cycles or until disease progression, intolerable toxicity, or participant withdrawal of consent. The FMT capsules are intended to modify the gut microbiome to reverse the resistance to the triple therapy and enhance the therapeutic response. | Other | FMT-Resistant HCC Cohort |
Primary outcome
Objective response rate, ORR
Time frame: Four weeks after the initiation of medication until the day before surgery
The Objective response rate (ORR) was defined as the complete response (CR) rate or the partial response (PR) rate according to RECIST1.1.
Adverse events
Time frame: From the initiation of medication, with recordings made whenever an adverse reaction occurs, assessed up to 12 months
Grade 1-5 AEs according to NCI-CTCAE V5.0.
6 secondary outcomes
Overall survival, OS
Time frame: From date of enrollment until the date of death from any cause, assessed up to 60 months
Progression free survival, PFS
Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Disease control rate, DCR
Time frame: Four weeks after the initiation of medication until the day before surgery
Gut Microbiome Composition after Fecal Microbiota Transplantation
Time frame: Baseline and at the end of each treatment cycle (up to 6 cycles)
Gut Microbiome Metabolomic Changes after Fecal Microbiota Transplantation
Time frame: Baseline and at the end of each treatment cycle (up to 6 cycles)
Gut Microbiome Immune Subset Variations after Fecal Microbiota Transplantation
Time frame: Baseline and at the end of each treatment cycle (up to 6 cycles)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatocellular Carcinoma Non-resectable, run by Fujian Provincial Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 16 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mao-Lin Yan (0591-88217140, yanmaolin74@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate, ORR (time frame: Four weeks after the initiation of medication until the day before surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2024.