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.
Biliary tract cancers include gallbladder cancer, intrahepatic cholangiocarcinoma, and perihilar cholangiocarcinoma.
HER2-positive by IHC or FISH
Age >=18 years.
ECOG performance status 0 - 2.
Distal cholangiocarcinoma
Known hypersensitivity or contraindications against gemcitabine, cisplatin, Nab- paclitaxel, or trastuzumab.
Clinically significant active coronary heart disease, cardiomyopathy, or congestive heart failure, NYHA III-IV.
Clinically significant valvular defect.
Parallel
Trastuzumab
DrugInj Trastuzumab given in a dose of 8mg/kg intravenously over 90 mins as first dose and subsequent doses at a dose of 6mg/kg intravenously over 30-60 minutes in 3 weekly cycle along with standard of care chemotherapy
Chemotherapy
DrugGemcitabine + cisplatin OR Gemcitabine-cisplatin-Nab-Paclitaxel given as a standard of care, chemotherapy as per the institutional guidlines
Progression-free survival (PFS)
the time from the time of diagnosis of an advanced disease to the time of disease progression or loss to follow-up or death, whichever is earlier
Overall survival (OS)
the time from the time of diagnosis to the time of death, lost to follow-up or last observation, whichever is earlier
Response rates
measured as per RECIST criteria in CE CT scan as compare with the baseline scans
Quality of life (QOL)
measured using the EORTC-QLQ-30 questionnaires All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level
Safety profile
side effects and adverse event profile with the combination will be reported as NCI-CTCAE v5.0
Click on the lead sponsor to view all of their trials.
