Trastuzumab Plus Chemotherapy vs Chemotherapy Alone in First-line HER2 Positive Advanced Biliary Tract Cancer Patients
Trial Parameters
Brief Summary
This is a randomized, open-label, two-arm, Phase III clinical trial evaluating the efficacy and safety of trastuzumab plus chemotherapy versus chemotherapy alone as first-line treatment in patients with HER2-positive advanced or metastatic biliary tract cancers (BTC). HER2-positive BTCs represent a molecular subset of these rare cancers, associated with poor prognosis and limited treatment options. Eligible patients with histologically confirmed HER2-positive (IHC 3+ or IHC 2+ with FISH amplification) unresectable or metastatic biliary tract adenocarcinoma-including gallbladder cancer, intrahepatic, and perihilar cholangiocarcinoma-will be randomized in a 1:1 ratio. Participants in the intervention arm (Arm A) will receive either gemcitabine and cisplatin with or without nab-paclitaxel plus trastuzumab, while those in the control arm (Arm B) will receive chemotherapy alone (gemcitabine + cisplatin with or without nab-paclitaxel). Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or death. The primary endpoint is 6-month progression-free survival (PFS). Secondary endpoints include overall survival (OS), response rate (RR), quality of life (QOL), and adverse event (AE) profiles. The study aims to enroll 196 patients across a single center in India over a period of 5 years, with an additional 6-month follow-up. This trial builds on earlier Phase II findings suggesting improved outcomes with trastuzumab in HER2-positive BTC and aims to provide the first randomized evidence for the benefit of HER2-targeted therapy in this setting.
Eligibility Criteria
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 relevan