1. Goals

   • The primary goal of this phase II trial is to:

   evaluate the response rate of combination chemotherapy with docetaxel and oxaliplatin in patients with locally advanced or metastatic BTC as first-line therapy

   Secondary goals are to:evaluate the treatment-related toxicities of this combination, investigate progression-free survival (PFS) and overall survival (OS) in this population

2. Design

The proposed clinical trial is an open label, non-comparative, multicenter phase II trial according to the two stage testing design by Simon.22

Inclusion Criteria:

1. Patients who were diagnosed as adenocarcinoma of gallbladder or biliary tract histologically or cytologically
2. Unresectable locally advanced, metastatic, or recurrent biliary tract cancer
3. Patients must be ≥ 18 years old of age
4. ECOG performance status ≤ 2 (see Appendix C)
5. At least one lesion that can be measured by imaging (CT/MRI) according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) (see Appendix D)
6. Estimated life expectancy of more than 3 months
7. Adequate bone marrow function (absolute neutrophil count [ANC] ≥ 1,500/µL, hemoglobin ≥ 9.0 g/dL [correction by transfusion is acceptable], and platelets ≥ 100,000/µL)
8. Adequate kidney function (serum creatinine < 1.5 x upper limit of normal [ULN])
9. Adequate liver function (serum total bilirubin < 3xULN; serum transaminases levels < 5xUNL)
10. Provision of fully informed consent prior to any study specific procedures

Exclusion Criteria:

1. Other tumor type than adenocarcinoma
2. Any previous history of chemotherapy for biliary tract cancer (prior neoadjuvant/adjuvant chemotherapy is allowed, if recurrence occurred more than 6 months after completion of previous chemotherapy)
3. Patients with second primary cancer (except, adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥5 years)
4. Patients who received radiotherapy on target lesion within 6 months prior to study treatment
5. Patients with defect of central nervous system (CNS) or any psychiatric disorders and CNS metastases
6. Patients who received major surgery within 4 weeks of starting study treatment or was not recovered from any effects of major surgery
7. Pregnant or breastfeeding women and women of childbearing potential not employing adequate contraception
8. Other serious illness or medical conditions A. Clinically significant cardiac disease (uncontrolled congestive heart disease despite treatment [NYHA class III or IV], symptomatic coronary artery disease, unstable angina or myocardial infarction, conduction abnormality like grade 2 AV block, serious arrhythmia needed for medication, uncontrolled hypertension) within 6 months prior to study entry B. Liver cirrhosis (≥ Child-Pugh class B) C. History of significant neurologic or psychiatric disorders including dementia or seizures D. Active uncontrolled infection E. Other serious underlying medical conditions which could impair the ability of the patient to participate in the study
9. Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy