Trastuzumab in HER2-positive Biliary Tract Cancer

Study Overview
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Brief Summary
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Trastuzumab is approved for the treatment of HER2-positive breast cancer and gastric cancer. The recent study showed that HER2 overexpression or amplification is noted about 5-15% of total biliary tract cancer patients. The aim of this study is to evaluate the efficacy and safety of trastuzumab in the combination of current standard gemcitabine plus cisplatin.

Official Title
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The Pilot Study of Trastuzumab in Combination With Gemcitabine Plus Cisplatin for HER2-positive Biliary Tract Cancer

Conditions
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Cholangiocarcinoma, Biliary Tract Cancer, HER-2 Protein Overexpression, HER-2 Gene Amplification

Intervention / Treatment
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* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject with disease that is not amendable to a curative treatment approach or locally advanced or metastatic or unresectable CCC with histological diagnosis At least one measurable(per RECIST 1.1) lesion Primary or metastatic tumor with HER2 positive defined on IHC2+, FISH+ or IHC3+ ECOG Performance status 0 or 1 At least 3 months for life expectancy Common inclusion criteria Men or women over 19 years at time of signing ICF Signed Informed Consent Form Exclusion Criteria: Received prior chemotherapy for advanced/metastatic disease (the adjuvant/neoadjuvant chemotherapy completed at least 6 months before enrolled will be accepted) Not recovery from toxicities related to any prior treatments excluding alopecia (eg, neurological toxicity to ≥ Grade 2) History of malignancy other than CCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death, such as carcinoma in situ or thyroid papillary carcinoma Hematology, chemistry or organ function ANC < 1.5 × 109/L, or Platelet < 100 × 109/L Total bilirubin > 1.5 × ULN; or AST/ ALT > 2.5 × ULN (or if the tumor has expanded into the liver, > 5 × ULN); or, alkaline phosphatase > 2.5 × ULN (or > 5 × if the tumor has expanded into the liver, or > 10 × ULN if the tumor has expanded into the brain without liver,); or albumin < 2.5 g/dL Creatinine clearance < 60 mL/min(calculated using the Cockcroft-Gault formula) Other exclusion criteria related to IP History of proved congestive heart failure; angina with medication; evidence of transmural myocardial infarction on ECG; uncontrolled hypertension(systolic> 180 mmHg or diastolic> 100 mmHg); clinically significant heart valve disease; uncontrolled arrhythmia LVEF < 50% (calculated by cardiac sonography or MUGA) Subject with rest dyspnea due to metastatic tumor or other disease or who needs oxygen therapy Chronic or high-dose corticosteroid treatment Clinically significant Hearing impairment Common exclusion criteria History or evidence of CNS metastases Interstitial pneumonia or pulmonary fibrosis with symptom and exact lesion on chest X-ray Hearing loss Uncontrolled significant systemic disease (eg, infection or uncontrolled DM) Pregnant or lactating females Sexually active fertile subjects without contraception Treatment with other investigational therapy within 4 weeks prior to initiation of study treatment Radiotherapy within 4 weeks prior to initiation of study treatment (the rest at least 2 weeks after palliative radiotherapy for bone metastasis and recovery from the effects of radiation will be accepted.) Major surgery within 4 weeks prior to initiation of study treatment History of HIV and active HBV or HCV Previously identified allergy or hypersensitivity to components of the study treatment formulations

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trastuzumab plus Gem/Cis<br>Gemcitabine 1,000 mg/m2 Day 1 and Day 8, every 3 weeks Cisplatin 25 mg/m2 Day 1 and Day 8, every 3 weeks Trastuzumab, every 3 weeks, 8 mg/kg at first cycle then, 6 mg/kg | Drug: Trastuzumab<br>* Trastuzumab plus gemcitabine/cisplatin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | Best response according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 | 6 months | 
| Adverse events | Adverse events graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Time between the initiation of chemotherapy and disease progression or death | 2 years | 
| Overall survival | Time between the initiation of chemotherapy and any cause of death | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cholangiocarcinoma, Biliary Tract Cancer, Trastuzumab