This study evaluates the efficacy and safety of second-line treatment of bortezomib in advanced intrahepatic cholangiocarcinoma patients.Half of participants will receive bortezomib while the other half will receive best supporting care.

There's no standard second-line treatment for advanced intrahepatic cholangiocarcinoma patients.

Previous study indicated high mutation/deletion rate of PTEN gene in intrahepatic cholangiocarcinoma and poor prognosis of those patients with PTEN mutation/deletion. The investigators also found that the activity of proteasomes elevated in cholangiocarcinoma cells with PTEN mutation/deletion.

So the investigators suppose proteasomes inhibitor could improve prognosis of intrahepatic cholangiocarcinoma patients with PTEN mutation/deletion

Inclusion Criteria:

1. Patients with a histologic or cytologic diagnosis of intrahepatic cholangiocarcinoma with stage IV;
2. Have progressed after at least 2 cycles of systematic chemotherapy therapy（gemcitabine+cisplatin/gemcitabine+oxaliplatin）;
3. The previous treatment and the present trial registration must be at least 2 weeks apart, and they must have recovered from any toxicity of a previous treatment;
4. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1;
5. Eastern Cooperative Oncology Group performance score (ECOG): 0-2; Life expectancy of at least 12 weeks;
6. Normal liver,kidney and bone marrow function；
7. Subjects who understand and voluntarily signed a written informed consent form.

Exclusion Criteria:

1. History of other malignancy within 3 years. Patients with central nervous system metastases or brain metastasis
2. There is any contraindication to use Bortezomib
3. Patients with contraindications (active bleeding, ulcers, intestinal perforation, intestinal obstruction, within 30 days after major surgery, uncontrolled high blood pressure medication, III-IV level cardiac insufficiency, severe liver and kidney dysfunction).
4. A previous history of Interstitial pulmonary disease, drug-induced interstitial disease, radiation pneumonitis requiring hormonal therapy or active interstitial lung disease with any clinical evidence.
5. Pregnant or lactating women.
6. History of radiation within 4 weeks prior to enrollment.