Hepatobiliary MalignancyPhase 2NCT07174947
SSRI Antidepressant Fluoxetine Improving Immunotherapy Efficacy in Advanced Hepatobiliary Malignancy Patients With Depression and Anxiety
A Phase 2 study testing Fluoxetine (drug) in people with Hepatobiliary Malignancy and Fluoxetine, run by First Affiliated Hospital of Wenzhou Medical University at 1 site in China.
Trial summary
Advanced liver and gallbladder malignancies (including liver cancer, cholangiocarcinoma and gallbladder cancer) are a type of disease that is difficult to treat, and most patients have a short survival period. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hepatobiliary Malignancy, Fluoxetine, Anxiety Disorders
- What is being tested?
- Fluoxetine (drug)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 240 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2025to 1 Dec 2027
- Phase
- Phase 2
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age: 18 to 80 years old, both male and female are acceptable.
- The histopathological/cytological diagnosis is hepatocellular carcinoma or cholangiocarcinoma. Hepatocellular carcinoma can be diagnosed by imaging.
- Patients with metastatic advanced or locally advanced liver and gallbladder malignancies;
- No treatment has been received and a first-line treatment regimen including PD-1 inhibitors /PD-L1 inhibitors is planned to be carried out;
- Patients with a PHQ-9 score of ≥10 or a GAD-7 score of ≥8, that is, those with positive screening for depression or anxiety;
- At least one lesion measurable by CT or MRI (with a maximum diameter of ≥0.5cm);
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- ECOG: 0-2;
- Child-Pugh score ≤7 points;
- The expected survival period is ≥12 weeks.
- Baseline blood cell count tests and blood biochemistry must meet the following standards:1) White blood cell count ≥3.0×10^9/L; Hemoglobin ≥90 g/L;2) Absolute neutrophil count ≥1.5×10^9/L;3) Platelet count ≥100×10^9/L;4) Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of the normal upper limit (ULN);5) Total bilirubin ≤ twice ULN;6) Serum creatinine ≤ 1.5 times ULN; Albumin ≥30 g/L;
- The subjects voluntarily joined this study, signed the informed consent form, had good compliance and cooperated with the follow-up.
Who cannot join
- Those with uncorrectable coagulation dysfunction and a distinct bleeding tendency;
- Patients who currently have unstable or active ulcers or gastrointestinal bleeding;
- Severe functional insufficiency of vital organs, such as severe cardiopulmonary insufficiency, etc;
- Patients with hepatic encephalopathy or intractable ascites requiring treatment;
- A history of mental disorders such as bipolar disorder, schizophrenia, and active suicidal ideation;
- Patients with active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (active is defined as a viral load > 20,000 IU/mL), or those who are positive for HBV or HCV and refuse to receive standardized antiviral treatment;
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- Unable to swallow oral medication;
- Patients allergic to fluoxetine;
- Currently using drugs that may have serious interactions with fluoxetine;
- The researchers assessed that the patient was unable or unwilling to comply with the requirements of the research protocol.
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
First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325000
Gang Chen, MD, Phd, 86+13616619566, chen.gang@wmu.edu.cn
About this study
Official title: SSRI Antidepressant Fluoxetine Improving Immunotherapy Efficacy in Advanced Hepatobiliary Malignancy Patients With Depression and Anxiety: A Randomized Controlled Clinical Trial
Advanced liver and gallbladder malignancies (including liver cancer, cholangiocarcinoma and gallbladder cancer) are a type of disease that is difficult to treat, and most patients have a short survival period. In recent years, immunotherapy (such as PD-1/PD-L1 inhibitors) has brought new hope to these patients, but still only a small number of patients can benefit.
Research has found that approximately 40% of patients with liver and gallbladder tumors have symptoms of depression and anxiety, which not only affect their quality of life but may also reduce the therapeutic effect by influencing immune function. Fluoxetine is a commonly used antidepressant. The latest research shows that in addition to improving mood, it may also enhance the anti-tumor effect of immunotherapy. This study aims to explore whether fluoxetine combined with immunotherapy can better control tumors than immunotherapy alone, prolong the survival period of patients, and at the same time improve the depressive and anxious symptoms and quality of life of patients.
- Being tested
- Fluoxetine (drug), Placebo
- Medical subject headings
- Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluoxetine (drug)Drug
Fluoxetine: Maintain at 20mg per day, orally, until disease progression or intolerance
PlaceboDrug
Placebo: 1 placebo tablet per day for maintenance, orally.
| Study group | Role | What they receive |
|---|---|---|
| Experimental Group | Experimental | 1. Standard treatment plan For patients with hepatocellular carcinoma, the first-line treatment regimen containing PD-1 inhibitors /PD-L1 inhibitors is adopted: 1) Toripalimab + bevacizumab 2) Tislelizumab 3) Nivolumab + ipilimumab For patients with cholangiocarcinoma, the combination of PD-1 inhibitors /PD-L1 inhibitors and gemcitabine + cisplatin/oxaliplatin (such as pembrolizumab +GEM -CDDP or durvalumab +GEM -CDDP) is adopted. 2. Fluoxetine: Maintain at 20mg per day, orally, until disease progression or intolerance. 3. The use of antiemetic, analgesic and other symptomatic treatment drugs is allowed, and all concurrent medication situations should be recorded. Receives: Drug: Fluoxetine (drug) |
| Control Group | Placebo comparator | 1. Standard treatment plan
For patients with hepatocellular carcinoma, the first-line treatment regimen containing PD-1 inhibitors /PD-L1 inhibitors is adopted:
1. Toripalimab + bevacizumab
2. Tislelizumab
3. Nivolumab + ipilimumab For patients with cholangiocarcinoma, the combination of PD-1 inhibitors /PD-L1 inhibitors and gemcitabine + cisplatin/oxaliplatin (such as pembrolizumab +GEM -CDDP or durvalumab +GEM -CDDP) is adopted.
2. Placebo: Take 1 placebo tablet per day for maintenance, orally.
3. The use of antiemetic, analgesic and other symptomatic treatment drugs is allowed, and all concurrent medication situations should be recorded. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) by mRECIST (%)
Proportion of participants achieving complete response (CR) or partial response (PR) based on mRECIST criteria, measured on contrast-enhanced CT/MRI at 4-12 weeks after treatment initiation.
Measured: at 4-12 weeks after treatment initiation
Secondary outcomes (4)
Overall Survival (OS) (months)
Time from treatment initiation to death from any cause.
Measured: 5 years
Progression-Free Survival (PFS) (months)
Time from treatment initiation to radiologically confirmed disease progression (mRECIST) or death from any cause, whichever occurs first.
Measured: 5 years
status of anxiety and depression
measured by psychologist using GAD-7 and PHQ-9, more than 10 points in either of the charts would be marked as positive
Measured: 5 years
Quality of Life Score (EORTC QLQ-C30, 0-100 scale)
Health-related quality of life will be assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30). Scores for global health status/QoL, functional scales, and symptom scales will be calculated according to the EORTC scoring manual, with higher scores indicating better functioning for functional scales and worse symptoms for symptom scales.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2025
- Study start1 Oct 2025
- Primary completion1 Oct 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatobiliary MalignancyStudies 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
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Wenzhou Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gang Chen, MD, First Affiliated Hospital of Wenzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07174947
- Sponsor's protocol ID
- SSRI
- Status last verified
- Sep 2025
- First submitted
- 8 Sep 2025
- Last updated
- 24 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: all IPD collected throughout the trial
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SSRI Antidepressant Fluoxetine Improving Immunotherapy Efficacy in Advanced Hepatobiliary Malignancy Patients With Depression and Anxiety: A Randomized Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT07174947
- Acronym / sponsor ID
- SSRI
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Wenzhou Medical UniversityUniversity, hospital or other
- Study start
- 1 Oct 2025 (actual)
- Primary completion
- 1 Oct 2027 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 16 Sep 2025 (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.
Advanced liver and gallbladder malignancies (including liver cancer, cholangiocarcinoma and gallbladder cancer) are a type of disease that is difficult to treat, and most patients have a short survival period. In recent years, immunotherapy (such as PD-1/PD-L1 inhibitors) has brought new hope to these patients, but still only a small number of patients can benefit.
Research has found that approximately 40% of patients with liver and gallbladder tumors have symptoms of depression and anxiety, which not only affect their quality of life but may also reduce the therapeutic effect by influencing immune function. Fluoxetine is a commonly used antidepressant. The latest research shows that in addition to improving mood, it may also enhance the anti-tumor effect of immunotherapy. This study aims to explore whether fluoxetine combined with immunotherapy can better control tumors than immunotherapy alone, prolong the survival period of patients, and at the same time improve the depressive and anxious symptoms and quality of life of patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental Group | Experimental | Drug: Fluoxetine (drug)1. Standard treatment plan For patients with hepatocellular carcinoma, the first-line treatment regimen containing PD-1 inhibitors /PD-L1 inhibitors is adopted: 1) Toripalimab + bevacizumab 2) Tislelizumab 3) Nivolumab + ipilimumab For patients with cholangiocarcinoma, the combination of PD-1 inhibitors /PD-L1 inhibitors and gemcitabine + cisplatin/oxaliplatin (such as pembrolizumab +GEM -CDDP or durvalumab +GEM -CDDP) is adopted. 2. Fluoxetine: Maintain at 20mg per day, orally, until disease progression or intolerance. 3. The use of antiemetic, analgesic and other symptomatic treatment drugs is allowed, and all concurrent medication situations should be recorded. |
| Control Group | Placebo comparator | Drug: Placebo1. Standard treatment plan For patients with hepatocellular carcinoma, the first-line treatment regimen containing PD-1 inhibitors /PD-L1 inhibitors is adopted: 1. Toripalimab + bevacizumab 2. Tislelizumab 3. Nivolumab + ipilimumab For patients with cholangiocarcinoma, the combination of PD-1 inhibitors /PD-L1 inhibitors and gemcitabine + cisplatin/oxaliplatin (such as pembrolizumab +GEM -CDDP or durvalumab +GEM -CDDP) is adopted. 2. Placebo: Take 1 placebo tablet per day for maintenance, orally. 3. The use of antiemetic, analgesic and other symptomatic treatment drugs is allowed, and all concurrent medication situations should be recorded. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age: 18 to 80 years old, both male and female are acceptable.
- The histopathological/cytological diagnosis is hepatocellular carcinoma or cholangiocarcinoma. Hepatocellular carcinoma can be diagnosed by imaging.
- Patients with metastatic advanced or locally advanced liver and gallbladder malignancies;
- No treatment has been received and a first-line treatment regimen including PD-1 inhibitors /PD-L1 inhibitors is planned to be carried out;
- Patients with a PHQ-9 score of ≥10 or a GAD-7 score of ≥8, that is, those with positive screening for depression or anxiety;
Key exclusion criteria (10 listed)
- Those with uncorrectable coagulation dysfunction and a distinct bleeding tendency;
- Patients who currently have unstable or active ulcers or gastrointestinal bleeding;
- Severe functional insufficiency of vital organs, such as severe cardiopulmonary insufficiency, etc;
- Patients with hepatic encephalopathy or intractable ascites requiring treatment;
- A history of mental disorders such as bipolar disorder, schizophrenia, and active suicidal ideation;
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 |
|---|---|---|
| Fluoxetine (drug)Fluoxetine: Maintain at 20mg per day, orally, until disease progression or intolerance | Drug | Experimental Group |
| PlaceboPlacebo: 1 placebo tablet per day for maintenance, orally. | Drug | Control Group |
Primary outcome
Objective Response Rate (ORR) by mRECIST (%)
Time frame: at 4-12 weeks after treatment initiation
Proportion of participants achieving complete response (CR) or partial response (PR) based on mRECIST criteria, measured on contrast-enhanced CT/MRI at 4-12 weeks after treatment initiation.
4 secondary outcomes
Overall Survival (OS) (months)
Time frame: 5 years
Progression-Free Survival (PFS) (months)
Time frame: 5 years
status of anxiety and depression
Time frame: 5 years
Quality of Life Score (EORTC QLQ-C30, 0-100 scale)
Time frame: 5 years
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 24 Mar 2026.
- Individual participant dataSharing planned: Yes. all IPD collected throughout the trial
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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.
First Affiliated Hospital of Wenzhou Medical University
Wenzhou, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fluoxetine (drug) in people with Hepatobiliary Malignancy and Fluoxetine, run by First Affiliated Hospital of Wenzhou Medical University at 1 site in China.
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 11 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 24 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) by mRECIST (%) (time frame: at 4-12 weeks after treatment initiation). 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 24 Mar 2026; AzTrials last refreshed its copy on 26 Oct 2026.