Fluoxetine added to immunotherapy for advanced liver and gallbladder cancer with depression or anxiety

SSRI Antidepressant Fluoxetine Improving Immunotherapy Efficacy in Advanced Hepatobiliary Malignancy Patients With Depression and Anxiety: A Randomized Controlled Clinical Trial

This trial will test whether adding the antidepressant fluoxetine to standard PD-1/PD-L1 immunotherapy helps people with advanced liver or gallbladder cancers who also have depression or anxiety.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 240 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: First Affiliated Hospital of Wenzhou Medical University (Academic / other)
• Drugs / interventions: immunotherapy
• Locations: 1 site (Wenzhou, Zhejiang)
• Trial ID: NCT07174947 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional study enrolls adults with advanced hepatocellular carcinoma or cholangiocarcinoma who screen positive for depression or anxiety and are starting first-line PD-1/PD-L1 therapy. Participants will receive either fluoxetine or a matching placebo in addition to planned immunotherapy, with regular imaging and clinical visits to monitor tumor response, survival, and mood symptoms. Key eligibility includes measurable disease, ECOG 0–2, Child-Pugh score ≤7, and adequate blood counts and chemistry. Outcomes will compare tumor control and survival between the fluoxetine and placebo groups while also tracking changes in depression and anxiety scores.

Who should consider this trial

Good fit: Adults 18–80 with advanced or metastatic hepatocellular carcinoma or cholangiocarcinoma who have not yet started first-line PD-1/PD-L1 therapy and who screen positive for depression (PHQ-9 ≥10) or anxiety (GAD-7 ≥8), with measurable disease, ECOG 0–2, Child-Pugh ≤7, and adequate laboratory values are ideal candidates.

Not a fit: Patients without depression or anxiety, those who are not eligible for PD-1/PD-L1 therapy, or those with poor liver function, very poor performance status, or prior systemic treatment are unlikely to benefit from joining this trial.

Why it matters

Potential benefit: If successful, adding fluoxetine could both improve how well immunotherapy controls tumors and help patients' mood and quality of life.

How similar studies have performed: Preclinical data and small clinical reports suggest SSRIs like fluoxetine may boost anti-tumor immunity, but combining fluoxetine with immunotherapy in larger controlled trials is largely novel and unproven.

Eligibility criteria

Inclusion Criteria:

* 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);
* 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.

Exclusion Criteria:

* 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;
* 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.

Where this trial is running

Wenzhou, Zhejiang

• First Affiliated Hospital of Wenzhou Medical University — Wenzhou, Zhejiang, China (Recruiting)

Conditions Hepatobiliary Malignancy; Fluoxetine; Anxiety Disorders; Depression Disorders