SIRT Followed by CIS-GEM Chemotherapy Versus CIS-GEM Chemotherapy Alone as 1st Line Treatment of Patients With Unresectable Intrahepatic Cholangiocarcinoma

This clinical study is a prospective, multicenter, randomized, controlled study evaluating
SIR-Spheres Y-90 resin microspheres followed by cisplatin-gemcitabine (CIS-GEM) chemotherapy
vs. CIS-GEM chemotherapy alone as first-line treatment of patients with unresectable
intrahepatic cholangiocarcinoma.

Randomized patients will be followed until death, withdrawal of consent, or until end of
study.

Inclusion Criteria:

- Willing, able and mentally competent to provide written informed consent.

- Aged 18 years or older.

- Histologically or cytologically confirmed unresectable and non-ablatable intrahepatic
cholangiocarcinoma.

- Liver-only or liver predominant intrahepatic cholangiocarcinoma. Patient are permitted
to have loco-regional lymph node involvement defined as: portal LN para aortic LN lesions < 1 cm if these lung lesions are positron emission tomography (PET) negative.

- Chemotherapy naïve. Adjuvant chemotherapy is not permitted.

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

- Adequate hematological function defined as:

Hemoglobin >/= 10g/dL White Blood Cell count (WBC) >/= 3.0 x 10^9/L Absolute neutrophil
count (ANC) >/= 1.5 x 10^9/L Platelet count >/= 100,000/mm^3 - Adequate liver function
defined as: Total bilirubin /= 30 g/L

- Adequate renal function defined as: Serum urea and serum creatinine < 1.5 times upper
limit of normal (ULN) Creatinine clearance >/= 45 ml/min (calculated with Cockcroft-Gault
Equation)

- Life expectancy of at least 3 months without any active treatment

- Female patients must either be postmenopausal, sterile (surgically or radiation- or
chemically-induced), or if sexually active use an acceptable method of contraception
during the study.

- Male patients must be surgically sterile or if sexually active must use an acceptable
method of contraception during the study.

- Considered suitable to receive either regimen in the clinical judgement of the
treating investigator.

Exclusion Criteria:

- Patients with only non-measurable lesions in the liver according to RECIST criteria

- Incomplete recovery from previous liver surgery, e.g. unresolved biliary tree
obstruction or biliary sepsis or inadequate liver function

- Biliary stent in situ

- Main trunk Portal Vein Thrombosis (PVT)

- Ascites, even if controlled with diuretics. (A minor peri-hepatic rim of ascites
detected at imaging is acceptable).

- Mixed hepatocellular carcinoma - intrahepatic cholangiocarcinoma (HCC-ICC) disease

- History of prior malignancy. Exceptions include in-situ carcinoma of the cervix
treated by cone-biopsy/resection, non-metastatic basal and/or squamous cell carcinomas
of the skin, recurrent intra-hepatic cholangiocarcinoma post local treatment or any
early stage (stage 1) malignancy adequately resected with curative intent at least 5
years prior to study entry

- Suspicion of any bone metastasis/metastases or central nervous system
metastasis/metastases on clinical or imaging examination.

- Prior internal or external radiation delivered to the liver.

- Pregnancy; breast feeding.

- Participation within 28 days prior to randomization, in an active part of another
clinical study that would compromise any of the endpoints of the study.

- Evidence of ongoing active infection that may affect treatment feasibility or outcome.

- Prior Whipple's procedure.