Yueju Pill Combined With Standard Therapy In Advanced Biliary Tract Cancer

Effect of Yueju Pill Combined With Standard Therapy on Quality of Life and Treatment Efficacy in Patients With Advanced Biliary Tract Cancer: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the impact of Yueju Pill on quality of life and treatment efficacy in patients with advanced biliary tract cancer (BTC) receiving standard therapy.

This multicenter, randomized, double-blind, placebo-controlled clinical trial aims to evaluate the impact of Yueju Pill on quality of life and treatment efficacy in patients with unresectable advanced or metastatic biliary tract cancer (BTC) receiving guideline-based standard chemotherapy. The study will be conducted at Zhongshan Hospital Affiliated with Fudan University, Xuhui District Central Hospital of Shanghai, Minhang District Central Hospital of Shanghai, and Shanghai Geriatric Medical Center. Eligible patients will be randomized into two groups: Group A (Intervention): Standard chemotherapy + Yueju Pill (6-9 g per dose, twice daily, orally until disease progression or intolerable toxicity). Group B (Control): Standard chemotherapy + placebo (identical in appearance, packaging, dosage, and administration frequency to Yueju Pill).

Inclusion Criteria:

Subjects must meet all of the following criteria to be enrolled in this study:

1. No gender restriction, age ≥18 years, and expected survival ≥3 months;

2. ECOG Performance Status (PS) of 0-1;

3. Child-Pugh class A;

4. Histologically confirmed diagnosis of advanced biliary tract cancer (BTC), including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, or gallbladder cancer;

5. At least one measurable lesion according to RECIST v1.1 criteria;

6. Planned to receive or currently receiving guideline-based, chemotherapy-centered systemic first- or second-line therapy;

7. Presence of mild to moderate anxiety or depressive symptoms (PHQ-9 or GAD-7 score of 5-14);

8. Adequate major organ function, including:

   1. Hematology (no blood transfusion or hematopoietic growth factors within 14 days): Hb ≥90 g/L, ANC ≥1.5×10⁹/L, PLT ≥90×10⁹/L, WBC ≥3.0×10⁹/L;
   2. Biochemistry: TBIL ≤1.5×ULN (≤2×ULN if liver metastases); ALT and AST ≤2.5×ULN (≤5×ULN if liver metastases); serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min; plasma albumin ≥30 g/L;
   3. Coagulation: INR and PT ≤1.5×ULN, APTT ≤1.5×ULN;
   4. Cardiac function: LVEF ≥50%, QTcF ≤450 msec (male) or ≤470 msec (female);
   5. Urine protein ≤2+, and if >2+, 24-hour urine protein must be ≤1.0 g;

9. Not pregnant or breastfeeding, and subjects of childbearing potential must use effective contraception during treatment and for 3 months after treatment;

10. Voluntary participation with signed informed consent, good compliance, and willingness to cooperate with follow-up.

Exclusion Criteria:

Subjects meeting any of the following criteria will not be eligible for this study:

1. Histological types of ampullary cancer, hepatocellular carcinoma, mixed-type liver cancer, or other malignancies not originating from bile duct cells;

2. History of or concurrent malignancy at other sites;

3. Severe anxiety or depression (PHQ-9 or GAD-7 score ≥15), currently receiving antidepressant or anti-anxiety medication, or history of substance abuse, alcoholism, or drug abuse;

4. Currently using other traditional Chinese medicine compound interventions;

5. Known allergy to monoclonal antibodies, anti-angiogenic drugs, gemcitabine, platinum drugs, or components of Chinese medicine;

6. Uncontrolled severe comorbidities, including:

   1. Congestive heart failure;
   2. Difficult-to-control hypertension;
   3. Angina or arrhythmias;
   4. Interstitial lung disease or active pulmonary tuberculosis;
   5. HBV DNA >2000 copies/mL or HCV RNA >1000 IU/mL after antiviral therapy;
   6. Known HIV positive or diagnosed with acquired immunodeficiency syndrome (AIDS);
   7. Clinically significant gastroesophageal variceal bleeding within 3 months prior to enrollment, or known bleeding tendency;
   8. Coagulation abnormalities (PT >14 sec), bleeding tendency, or currently receiving anticoagulant/thrombolytic therapy;
   9. Known or suspected active autoimmune disease, or requiring long-term systemic immunosuppressive therapy or corticosteroids;

7. Other factors that, in the investigator's judgment, may affect patient safety or trial compliance (e.g., severe laboratory abnormalities, psychiatric disorders, lack of family or social support).