Hepatocellular Carcinoma (HCC)Phase 2NCT07463248
PULSAR Combined With Fecal Microbiota Transplantation for Advanced Hepatocellular Carcinoma Progressing After First-Line Targeted-Immunotherapy
A Phase 2 study testing Tislelizumab Combined With TKI, Fecal Microbiota Transplantation and PULSAR in people with Hepatocellular Carcinoma (HCC), run by Wang Xin at 1 site in China.
Trial summary
This is an open-label, multicenter, randomized controlled Phase II trial. Patients with advanced hepatocellular carcinoma (HCC) who developed secondary resistance to first-line targeted-immunotherapy were randomly assigned to receive either the original first-line targeted-immunotherapy combined with FMT and PULSAR… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma (HCC)
- What is being tested?
- Tislelizumab Combined With TKI, Fecal Microbiota Transplantation and PULSAR
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteChina
- Study dates
- 15 Apr 2026to 31 Jan 2029
- Phase
- Phase 2
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
Who may be able to join
- Clinically or pathologically confirmed unresectable primary hepatocellular carcinoma;
- Liver cancer patients with BCLC stage B or C;
- Not receiving systematic treatment before enrollment;
- Patients with acquired resistance who achieved disease control (DCR: CR, PR, or SD) following first-line targeted-immunotherapy but later experienced disease progression (PD);
- Child Pugh score ≤ 7 points;
- Subject must have at least 1 measurable target lesion examined by CT or MRI according to RECIST1.1 criteria;
- The Eastern Oncology Consortium (ECOG) Behavioral status score was 0 or 1.
Who cannot join
- Failure to recover to NCI-CTC AE Grade ≤1 (excluding alopecia and fatigue) or to baseline level from toxicities and/or complications of prior interventions before PD-1 monoclonal antibody re-challenge;
- Subjects requiring systemic therapy with corticosteroids (>10 mg prednisone equivalent daily) or other immunosuppressive agents within 14 days prior to PD-1 monoclonal antibody re-challenge；
- Received abdominal radiotherapy or administered radioactive substances within 28 days prior to PD-1 monoclonal antibody re-challenge;
- History of gastrointestinal perforation and/or fistula within 6 months prior to PD-1 monoclonal antibody re-challenge;
- Active gastrointestinal bleeding within 1 week before the first fecal microbiota transplantation.
- Occurrence of infection within 28 days prior to PD-1 monoclonal antibody re-challenge;
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- Active infection requiring systemic antimicrobial therapy before PD-1 monoclonal antibody re-challenge and intestinal microbiota transplantation, excluding local infections requiring only topical antibiotics (e.g., skin infections);
- Received live or attenuated vaccines within 30 days prior to PD-1 monoclonal antibody re-challenge, or planned vaccination during the study period;
- Known history of primary immunodeficiency or HIV infection;
- Active or previously documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, chronic diarrhea), except patients with chronic diarrhea who had no recurrence within 2 years before enrollment;
- Known history of active tuberculosis (TB)；
- Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
- Suffering from active, known or suspected autoimmune disease, or with a history of autoimmune disease;
- History of cardiovascular or cerebrovascular events or accidents within 6 months;
- Other conditions deemed by the investigator to be inappropriate for enrollment, including patients with hyperprogressive disease.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
West China Hospital
Chengdu, Sichuan, 610041
Feng Wen, +86 28 85422589, 172571964@qq.com
About this study
Official title: Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy (PULSAR) Combined With Fecal Microbiota Transplantation (FMT) for Reversing Resistance to First-Line Targeted-Immunotherapy in Advanced HCC: A Clinical Application Study
This is an open-label, multicenter, randomized controlled Phase II trial. Patients with advanced hepatocellular carcinoma (HCC) who developed secondary resistance to first-line targeted-immunotherapy were randomly assigned to receive either the original first-line targeted-immunotherapy combined with FMT and PULSAR (experimental group), or second-line targeted-immunotherapy (control group). The first-line targeted-immunotherapy regimens consisted of tislelizumab combined with one of the first-line evidence-based tyrosine kinase inhibitors (TKIs), including lenvatinib, donafenib, apatinib, and sorafenib. Given that this study enrolled patients who progressed after an initial response to first-line targeted-immunotherapy, the second-line regimen in the control group continued tislelizumab immunotherapy while switching the TKI to regorafenib, an agent with second-line evidence.
Read the detailed description
Based on previous studies, the investigators aim to further explore the difference in efficacy between continuing the original targeted-immunotherapy regimen combined with FMT and PULSAR, versus standard second-line therapy, in patients with acquired resistance who experienced disease progression (PD) after achieving disease control (CR, PR or SD) with first-line targeted-immunotherapy.
The investigators will investigate whether fecal microbiota transplantation reshapes the tumor immune microenvironment by altering gut microbiota composition, and whether it can enhance immunogenicity and reverse the efficacy of immunotherapy plus TKI treatment when combined with radiotherapy. The investigators will also explore the immune-activating effect and synergistic mechanism of the PULSAR radiotherapy modality.
Primary Objective: Progression-Free Survival (PFS); Secondary Objectives: Overall Survival (OS), Objective Response Rate (ORR), Disease Control Rate (DCR), incidence and severity of Adverse Events (AE), changes in gut microbiota indices, and changes in tumor immune microenvironment indices.
- Conditions
- Hepatocellular Carcinoma (HCC)
- Being tested
- Tislelizumab Combined With TKI, Fecal Microbiota Transplantation, PULSAR
- Keywords
- Advanced Hepatocellular Carcinoma, Fecal Microbiota Transplantation (FMT), PULSAR, targeted-immunotherapy, reverse drug resistance
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tislelizumab Combined With TKIDrug
Tislelizumab: 200mg, intravenous infusion, once every 3 weeks, D1. Targeted therapy (TKI): first-line treatment options such as lenvatinib, donafenib, apatinib, sorafenib, etc. The second-line control group was treated with Regorafenib 80mg once a day, taken for three weeks and rested for one week.
Combination therapy is administered every 21 days as a cycle until disease progression, death, or intolerable toxicity occurs.
Fecal Microbiota TransplantationDrug
Fecal Microbiota Transplantation (FMT): 30g, orally administered, once every 3 weeks, D-3 (3 days before systemic treatment). After the preparation of the microbiota solution or capsule, store it in a -80 ℃ refrigerator. Transfer the microbiota solution or capsule to room temperature and seal it 15 minutes before use. Fasting is required 4 hours before microbiota transplantation and 1 hour after transplantation.
PULSARRadiation
Also called Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy
PULSAR : Choose 3-5 lesions, but cannot include all newly progressing lesions (new progressing lesions must not be treated with radiotherapy to observe efficacy), once a month for 8Gy, for a total of 3-5 times.
| Study group | Role | What they receive |
|---|---|---|
| PULSAR Combined with FMT and the Original Regimen | Experimental | The experimental group patients will receive PULSAR combined with FMT and the original first-line target immunotherapy regimen (Tislelizumab+TKI) as second-line treatment until disease progression, death, or intolerable toxicity occurs. Receives: Drug: Tislelizumab Combined With TKI; Drug: Fecal Microbiota Transplantation; Radiation: PULSAR |
| Standard second-line treatment | Active comparator | The control group patients will receive second-line treatment with Tislelizumab combined with regorafenib until disease progression, death, or intolerable toxicity occurs. Receives: Drug: Tislelizumab Combined With TKI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS)
PFS is defined as the time from the date of randomization until the date of disease progression according to RECIST 1.1 or death by any cause.
Measured: From randomization to the first occurrence of disease progression or death from any cause up to approximately 24 months
Secondary outcomes (6)
Overall Survival (OS)
OS is defined as the time from the date of randomization until death due to any cause.
Measured: From randomization to death due to any cause up to approximately 24 months
Objective Response Rate (ORR)
ORR (per RECIST 1.1 as assessed by the Investigator) was defined as the number (%) of participants with at least 1 confirmed visit response of CR or PR until progression, or the last evaluable assessment in the absence of progression.
Measured: From date of randomization until the date of first documented progression, assessed up to 24 months
Disease Control Rate (DCR)
Number (%) of participants with CR, PR, or SD.
Measured: From date of randomization until the date of first documented progression, assessed up to 24 months
Number of participants with adverse events (AEs)
Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0, vital signs, and clinical laboratory test results in the Safety Analysis Set
Measured: Up to 24 months
Changes in gut microbiota indicators
Changes in patient microbiome will be determined by analysis of gut bacterial composition in patient stool samples at baseline and post-FMT.
Measured: At baseline (prior to FMT), first efficacy evaluation (approximately 9 weeks post-FMT), and exit from the group
Changes in tumor immune microenvironment indicators
Effects on the patient immune microenvironment will be assessed by examining changes in peripheral blood immune cells （including CD3, CD4, CD8 T cells, B cells, macrophages, NK cells, Th1, Th2, Th17, and Treg cells）at baseline and post-FMT.
Measured: At baseline (prior to FMT), first efficacy evaluation (approximately 9 weeks post-FMT), and exit from the group
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2026
- Study start15 Apr 2026
- Primary completion31 Jan 2028 (estimated)
- Study completion31 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma (HCC)Studies 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wang Xin
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Wang Xin, West China Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07463248
- Sponsor's protocol ID
- PROFIT
- Status last verified
- Feb 2026
- First submitted
- 28 Feb 2026
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided