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

Prospective, Multicenter, Randomized, Controlled Study Evaluating SIR-Spheres Y-90 Resin Microspheres Preceding Cisplatin-gemcitabine (CIS-GEM) Chemotherapy Versus CIS-GEM Chemotherapy Alone as First-line Treatment of Patients With Unresectable Intrahepatic Cholangiocarcinoma

The study planned to evaluate the benefit of applying Selective Internal Radiation Therapy (SIRT) using SIR-Spheres Y-90 resin microspheres prior to receiving systemic chemotherapy treatment (cisplatin-gemcitabine, or CIS-GEM) in patients with unresectable intrahepatic cholangiocarcinoma. Half of the patients were randomized to CIS-GEM chemotherapy plus SIRT, and half of the patients were randomized to CIS-GEM alone.

This clinical study was 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 were to 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 </= to 2 cm and/or para aortic LN </= to 1.5 cm in longest diameter, and/or up to 2 indeterminate lung 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 umol/L (1.75 mg/dL) Albumin >/= 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.