Trastuzumab-pkrb Combined With Modified FOLFOX-6 in Biliary Tract Cancer Patients Progressed on First Line Therapy

This phase II study is designed to see whether trastuzumab-pkrb+FOLFOX is active as 2nd or 3rd line treatment for HER2-positive biliary tract cancer patients.

Inclusion criteria

• Histologically documented recurred/metastatic/unresectable biliary tract cancer, including gallbladder cancer, intrahepatic, extrahepatic cholangiocarcinoma, or ampulla of vater cancer.
• Histologically confirmed HER2 positive biliary tract cancer. HER2-positive tumor was defined as either IHC 3+ or IHC 2+ in combination with ISH +, or ERBB2 amplification (≥6 copies) by tumor tissue NGS.
• Recurred/metastatic/unresectable biliary tract cancer patient whose disease progression was confirmed by imaging modality after gemcitabine+cisplatin containing 1st line palliative chemotherapy regimen. Previous lines should be one or two (immunotherapy monotherapy not counted).
• be willing and able to provide written informed consent/assent for the trial
• be at least 19 years of age on day of signing informed consent
• have measurable disease based on RECIST (Response Evaluation Criteria In Solid Tumors) version 1.1
• have a performance status of 0 or 1 on the ECOG (Eastern Cooperative Oncology Group) Performance Scale
• demonstrate adequate organ function
• No severe valvular or arrhythmic cardiac disease with LVEF ≥ 50%
• female subject of childbearing potential should have a negative urine or serum pregnancy or be willing to use birth control

Exclusion criteria

• Previous treatment history of oxaliplatin containing chemotherapy, anti-HER2 targeting treatment (trastuzumab, neratinib, lapatinib, and etc)
• has had a prior anti-cancer chemotherapy, targeted small molecule therapy, or radiotherapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered.
• has a known additional malignancy that is progressing or requires active treatment within 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin and thyroid cancer that has undergone potentially curative therapy or in situ cervical cancer
• has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• has known history or evidence of any disease, treatment, or laboratory results that would inhibit the patient's participation to the study.
• Has clinically significant cardiac disease, including congestive heart failure ≥ NYHA grade 2, uncontrolled hypertension, QTcF > 470 msec or QT prolong syndrome, recent myocardiac infarction or unstable angina history
• has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
• has known active Hepatitis B (HBsAg reactive and HBV DNA 100 ≥copies/ml) or Hepatitis C (anti-HCV reactive and HCV RNA [qualitative] is detected)
• has received a live vaccine within 30 days of planned start of study therapy.
• has an active infection requiring systemic therapy
• has history of severe adverse event or allergic reaction to 5-FU, leucovorin, oxaliplatin or trastuzumab
• need O2 supply or show dyspnea on rest due to advanced malignancy