Trastuzumab Plus Chemotherapy vs Chemotherapy Alone in First-line HER2 Positive Advanced Biliary Tract Cancer Patients

Inclusion Criteria: Histologically confirmed adenocarcinoma of the biliary tract, with the following specifications - 1. Biliary tract cancers include gallbladder cancer, intrahepatic cholangiocarcinoma, and perihilar cholangiocarcinoma. 2. HER2-positive by IHC or FISH 3. Age \>=18 years. 4. ECOG performance status 0 - 2. 5. Unresectable or metastatic cancer. 6. Patient does not have any contraindications to receive chemotherapy or trastuzumab. 7. Adequate hematological, hepatic, and renal function parameters- Hematological- Hb\> 80 g/L, ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L. Liver functions- bilirubin ≤ 2 x upper limit normal (ULN), AST/ALT ≤ 5 x ULN, alkaline phosphatase ≤ 6 x upper limit normal (ULN) S. albumin ≥ 30 g/L. Renal function- Creatinine ≤ 1.5 ULN, Creatinine clearance \>= 30 mL/min. 8. Normal cardiac ejection fraction and cardiac function, as assessed by echocardiography, ejection fraction (EF) \>=50% or above the lower limit of normal. ECG with no clinically relevant abnormalities. 9. Women of childbearing age should have a negative pregnancy test at the time of randomization and should be willing to use adequate contraception during the treatment phase of the trial. 10. Subjects must provide written informed consent prior to the performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow-up assessments and procedures. 11. Subjects who have received adjuvant chemotherapy will be considered eligible provided that therapy is completed more than 12 months before study enrollment. Patients who have received radiation therapy and surgery will also be eligible provided the interventions have been completed 3 and 2 weeks, respectively, before enrolment in the study. 12. Negative serum pregnancy test (if applicable) and willing for adequate contraception. 13. At least one measurable disease according to RECIST criteria. 14. Life expectancy of at least 12 weeks. Exclusion Criteria: 1. Distal cholangiocarcinoma 2. Known hypersensitivity or contraindications against gemcitabine, cisplatin, Nab- paclitaxel, or trastuzumab. 3. Clinically significant active coronary heart disease, cardiomyopathy, or congestive heart failure, NYHA III-IV. 4. Clinically significant valvular defect. 5. Past or current history of other malignancies not curatively treated and without evidence of disease for more than 5 years, except for curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix. 6. Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy. 7. Baseline neuropathy \> NCI Grade I. 8. Subject pregnant or breastfeeding, or planning to become pregnant within 6 months after the end of treatment. 9. Received prior chemotherapy within 1 year. 10. Any active ILD/ history of lung illness requiring bronchodilator drugs. 11. Patients with prior chemotherapy for metastatic disease will be ineligible for enrollment in the study.