Biliary Tract Cancer (BTC)
Conditions
Keywords
Biliary Tract Cancer, Yueju Pill, Quality of Life, Treatment Efficacy
Brief summary
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.
Detailed description
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).
Interventions
DRUGYueju Pill + Standard Anti-tumor Therapy
Group A (Intervention): Standard therapy + Yueju Pill (6-9 g per dose, twice daily, orally until disease progression or intolerable toxicity).
DRUGPlacebo + Standard anti-tumor therapy
Group B (Control): Standard therapy + placebo (identical in appearance, packaging, dosage, and administration frequency to Yueju Pill).
Sponsors
Shanghai Zhongshan Hospital
Shanghai Geriatric Medical Center
Minhang Central Hospital
Xuhui Central Hospital, Shanghai
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This study is double-blind. Subjects, investigators, site staff, CRCs, and assessors will remain blinded to the intervention (Yueju Pill or placebo). Study drug and placebo are identical in appearance, packaging, color, odor, specifications, and labeling. Standard-of-care treatment is not blinded.
Intervention model description
Randomized Controlled Trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in quality of life | 18 week after treatment | The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 v3) was used to assess changes (Δ) in quality-of-life scores from baseline to week 18 after treatment. Scores on the EORTC QLQ-C30 range from 0 to 100, with higher scores indicating better global health status/quality of life. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | 1 year | defined according to RECIST v1.1 criteria, calculated as the proportion of patients achieving complete response (CR), partial response (PR), or stable disease (SD) among all evaluable patients (CR + PR + SD). |
| Objective response rate (ORR) | 1 year | defined according to RECIST v1.1 criteria, calculated as the proportion of patients achieving complete response (CR) or partial response (PR) among all evaluable patients (CR + PR). |
| European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score | 1 year | The EORTC QLQ-C30 is a 30-item validated instrument assessing cancer-related quality of life across domains including physical, role, emotional, cognitive, and social functioning. Scores are transformed to a 0-100 scale. For functional and global health/QoL scales, higher scores indicate better quality of life. For symptom scales, higher scores indicate worse symptoms. |
| European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Cholangiocarcinoma Module (EORTC QLQ-BIL21) Score | 1 year | The EORTC QLQ-BIL21 is a 21-item validated module designed for patients with cholangiocarcinoma, assessing disease-related symptoms and impact. Scores are transformed to a 0-100 scale, with higher scores indicating worse symptoms. |
| Overall survival (OS) | 1 year | defined as the time from randomization to death from any cause or to the date of the last follow-up, whichever occurs first. |
| Progression-free survival (PFS) | 1 year | defined as the time from randomization to the first documented disease progression by imaging or death from any cause, whichever occurs first. |
| Patient Health Questionnaire-9 (PHQ-9) Score | 1 year | The Patient Health Questionnaire-9 is a 9-item self-report instrument measuring depressive symptoms. Scores range from 0 (no depressive symptoms) to 27 (severe depression). Higher scores indicate worse depressive symptoms. |
| Generalized Anxiety Disorder-7 (GAD-7) Score | 1 year | The Generalized Anxiety Disorder-7 is a 7-item self-report instrument measuring anxiety symptoms. Scores range from 0 (no anxiety symptoms) to 21 (severe anxiety). Higher scores indicate worse anxiety symptoms. |
| Change in Traditional Chinese Medicine (TCM) syndrome score | 1 year | the study-specific TCM Syndrome Information Scale will be used to assess changes and improvement in patients' TCM syndrome characteristics before and after treatment. Scores range from 0 to 100, with higher scores indicating more severe TCM symptoms (worse outcome). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serum Amino Acid Concentrations | Baseline and at the end of each treatment cycle (each cycle is 21 days) during the treatment period. | Peripheral blood levels of selected amino acids (e.g., tryptophan, glutamine, arginine) will be measured as metabolic biomarkers using liquid chromatography-mass spectrometry (LC-MS).Unit of Measure: μmol/L |
| Composite Distribution of Peripheral Immune Cell Subsets | Baseline and at the end of each treatment cycle (each cycle is 21 days) during the treatment period. | The proportion of major immune cell subsets in peripheral blood will be assessed by flow cytometry. The composite outcome includes: T lymphocytes (CD3+) CD4+ T cells (CD3+CD4+) CD8+ T cells (CD3+CD8+) B lymphocytes (CD19+ or CD20+) Natural killer (NK) cells (CD3-CD56+ and/or CD16+CD56+) Each component will be reported as the percentage of peripheral blood mononuclear cells (PBMCs). The composite outcome is defined as the 5-component vector of these percentages, with summary statistics (mean, SD, median, IQR) and changes from baseline presented for each subset.Unit of Measure: % of PBMCs |
| Inflammatory Cytokine Panel Score | Baseline and at the end of each treatment cycle (each cycle is 21 days) during the treatment period. | A composite score reflecting systemic inflammatory cytokine burden will be calculated from serum/plasma concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-2 receptor (IL-2R), interleukin-8 (IL-8), and interleukin-10 (IL-10). For each cytokine, values will be standardized as z-scores relative to the study population, and the panel score will be defined as the sum of these standardized values. Higher scores indicate a higher overall inflammatory cytokine burden. |
| Serum Epinephrine/Norepinephrine Concentration | 1 year | Epinephrine/Norepinephrine levels in peripheral blood will be measured as a stress-related catecholamine biomarker. Concentrations will be quantified using immunoassay.Unit of Measure: pg/mL |
| Serum Serotonin (5-HT) Concentration | Baseline and at the end of each treatment cycle (each cycle is 21 days) during the treatment period. | Peripheral blood serotonin (5-HT) levels will be measured as a neurotransmitter biomarker. Concentrations will be quantified using immunoassay or high-performance liquid chromatography (HPLC).Unit of Measure: ng/mL |
| Serum Gamma-Aminobutyric Acid (GABA) Concentration | Baseline and at the end of each treatment cycle (each cycle is 21 days) during the treatment period. | GABA levels in peripheral blood will be measured as an inhibitory neurotransmitter biomarker. Concentrations will be quantified using immunoassay or LC-MS.Unit of Measure: μmol/L |
| Serum Cortisol Concentration | Baseline and at the end of each treatment cycle (each cycle is 21 days) during the treatment period. | Cortisol levels in peripheral blood will be measured as a biomarker of stress response. Concentrations will be quantified using immunoassay.Unit of Measure: μg/dL |
| Incidence of treatment-related adverse events (AE/SAE) | 1 year | all adverse events will be recorded and graded according to the NCI CTCAE v5.0 criteria, including but not limited to nausea, vomiting, and hepatic function abnormalities, with frequency and severity summarized. |
Countries
China
Contacts
Primary ContactGuoming Shi, Professor
Backup ContactYixiao Zhang, M.D.
Outcome results
None listed