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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Given PO
Correlative studies
Undergo yttrium Y-90 radioembolization
City of Hope Medical Center
Duarte, California, United States
Incidence of dose limiting toxicities (DLT) defined as any grade 3 or above toxicity assessed by the National Cancer Institute Common Terminology for Adverse Events version 4.0
The toxicities observed at each dose level will be summarized in terms of type, severity, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities. Tabular and graphical summaries will be used to explore the relationship of type and grade toxicity to other clinical parameters such as disease response and the presence of other comorbidities.
Time frame: Up to day 45
Duration of response according to RECIST v1.1, mRECIST, and EASL criteria
Duration of response will be calculated independently of PFS in order to evaluate the possibility that progression may occur after an initial tumor shrinkage.
Time frame: Time until tumors progress beyond the values measured at baseline, assessed up to 48 months
Levels of CA 19-9 response
CA 19-9 will be assessed after Y-90 and will be compared to other measures of disease response using Pearson correlation or similar methods.
Time frame: Up to 48 months
Liver-specific PFS according to RECIST v1.1, mRECIST, and EASL criteria
Evaluated using Kaplan-Meier analysis.
Time frame: Time until tumors progress beyond the values measured at baseline, assessed up to 48 months
Overall survival
Evaluated using Kaplan-Meier analysis.
Time frame: Up to 48 months
PFS according to RECIST v1.1, mRECIST, and EASL criteria
Evaluated using Kaplan-Meier analysis.
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Time frame: Time until tumors progress beyond the values measured at baseline, assessed up to 48 months
Rate of conversion to surgical candidacy
Time frame: Up to 48 months