Capecitabine and Y-90 Radioembolization in Treating Patients With Advanced Bile Duct Cancer in the Liver That Cannot Be Removed by Surgery
Capecitabine and Y-90 Radioembolization in Treating Patients With Advanced Bile Duct Cancer in the Liver That Cannot Be Removed by Surgery
This phase I trial studies the side effects of capecitabine and Y-90 radioembolization in
 treating patients with bile duct cancer in the liver that has spread to other places in the
 body and cannot be removed by surgery. Radiation therapy, such as Y-90 radioembolization,
 injects tiny radioactive Y-90 microspheres into the blood supply next to the liver tumors to
 kill tumor cells. Capecitabine may make radiation more effective. Giving capecitabine and
 Y-90 radioembolization may work better in treating patients with bile duct cancer in the
 liver.
PRIMARY OBJECTIVES:

 I. To evaluate the safety and toxicity of capecitabine, to be used in combination with
 yttrium Y-90 (yttrium 90) (Y-90) radioembolization (RE), in patients with a diagnosis of
 unresectable intrahepatic cholangiocarcinoma (ICC).

 SECONDARY OBJECTIVES:

 I. To describe the toxicities associated with Y-90 + capecitabine in patients with ICC.

 II. To develop a preliminary assessment of efficacy by evaluating liver-specific
 progression-free survival (PFS) and overall PFS.

 III. To develop a preliminary assessment of efficacy by evaluating response rate according to
 Response Evaluation Criteria in Solid Tumors (RECIST)/modified RECIST (mRECIST) and the
 Europeans Association for the Study of the Liver (EASL) imaging criteria.

 IV. To develop a preliminary assessment of efficacy by evaluating cancer antigen (CA) 19-9
 response and its correlation with imaging markers of tumor response.

 V. To develop a preliminary assessment of efficacy by evaluating duration of response in the
 liver, as measured by the time for target liver lesions to progress according to
 RECIST/mRECIST beyond size at study enrollment.

 VI. To develop a preliminary assessment of efficacy by evaluating rate of conversion to
 surgical resection for subjects who are surgically unresectable at presentation due to size
 or location of hepatic lesions (excluding subjects with extrahepatic disease or medically
 inoperable at presentation).

 VII. To develop a preliminary assessment of efficacy by evaluating overall survival.

 OUTLINE:

 Patients undergo yttrium Y 90 resin microspheres radioembolization over 60-90 minutes on day
 1. Patients receive capecitabine orally (PO) twice daily (BID) on days 1-14.

 After completion of study treatment, patients are followed up every 2 months.
Inclusion Criteria:

 -  Documented informed consent of the participant and/or legally authorized
 representative

 -  Eastern Cooperative Oncology Group performance status 0-2

 -  Life expectancy > 3 months

 -  Intrahepatic cholangiocarcinoma; a histological diagnosis is mandated; a diagnosis of
 adenocarcinoma with staining pattern consistent with cholangiocarcinoma and with a
 clinical presentation consistent with cholangiocarcinoma will be acceptable for
 enrollment as this is a typical intrahepatic cholangiocarcinoma presentation

 -  Primary tumor deemed unresectable by hepatobiliary surgeon

 -  Absence of the following:

 -  Malignant ascites

 -  Extensive carcinomatosis (in the opinion of the investigator)

 -  Bulky, diffuse adenopathy (> 5 lymph nodes > 2 cm each)

 -  Extensive metastatic disease to the lungs (> 5 tumors > 2 cm each)

 -  Has completed pre-RE angiogram up to 3 weeks prior to Y-90 therapy

 -  Lung shunt fraction =< 20% and anatomy amenable to intra-arterial radiation
 delivery

 -  Extrahepatic vessels deemed at risk for radiation injury were successfully
 embolized

 -  Prior systemic chemotherapy must be completed > 2 weeks of radioembolization

 -  Negative serum or urine beta-human chorionic gonadotropin (HCG) test (female patient
 of childbearing potential only)

 -  Platelets (PLT) >= 100,000/mm^3

 -  Absolute neutrophil count (ANC) >= 1500 cells/mm^3

 -  Creatinine clearance of > 50 mL/min per 24 hour urine collection of the
 Cockcroft-Gault formula

 -  Hemoglobin > 9 g/dL

 -  Total bilirubin < 2 mg/dL

 -  Agreement by females of childbearing potential and sexually active males to use an
 effective method of contraception (hormonal or barrier method of birth control or
 abstinence) prior to study entry and until at least 180 days after administration of
 any study agent; should a woman become pregnant or suspect that she is pregnant while
 participating on the trial, she should inform her treating physician immediately

 Exclusion Criteria:

 -  Prior selective internal radiation to the liver

 -  Prior warfarin-based therapies within 7 days of capecitabine treatment

 -  Actively receiving any other investigational agents, or concurrent biological,
 chemotherapy, or radiation therapy

 -  Neuropathy >= grade 2 (moderate neuropathy that limits instrumental activities of
 daily living)

 -  History of main or lobar portal vein thrombosis

 -  History of biliary stent, internal biliary drain, or prior procedure compromising the
 ampulla of Vater (diagnostic endoscopic retrograde cholangiopancreatography [ERCP] is
 permissible)

 -  Known dihydropyrimidine dehydrogenase deficiency

 -  History of allergic reactions attributed to:

 -  Study agent or its metabolites

 -  Iodinated contrast media

 -  Pregnant or breastfeeding (women)

 -  Concurrent diagnosis of other active malignancies with the exception of ductal
 carcinoma in situ, cervical carcinoma in situ, and localized non-melanoma skin cancer

 -  Any clinically significant uncontrolled illness including ongoing active infection

 -  Prospective participants who, in the opinion of the investigator, may not be able to
 comply with all study procedures (including compliance issues related to
 feasibility/logistics)