Study Of Intrahepatic Arterial Injection of 90-Y Glass Microspheres for Cholangiocarcinoma

Study Overview
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Brief Summary
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The purpose of this study is to see if Therasphere will be a better way to treat cholangiocarcinoma. The investigators want to find out what effects, good and/or bad, this treatment will have on the patient and their cancer.

Detailed Description
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The goal of treatment with TheraSphere is to allow a large dose of radiation to be delivered directly to the tumor with less risk of toxic effects from radiation to other parts of the body or to healthy liver tissue when compared with currently available treatments. The standard treatment for cholangiocarcinoma is surgery (if possible), external beam radiation therapy and/or chemotherapy. External beam radiation therapy to the liver may reduce symptoms, but only 20% of patients experience significant tumor shrinkage. Chemotherapy has response rates ranging from 6-19%. More recently, a new approach has been developed, called TheraSphere. Based on the results of earlier studies with TheraSphere, the study doctors at Moffitt feel this is a reasonable alternative to the standard treatment for this disease. TheraSphere has restricted approval from the United States Food and Drug Administration (FDA) for the treatment of hepatocellular liver cancer; but it has not yet been approved for the treatment of cholangiocarcinoma. TheraSphere is a medical device containing yttrium-90 (Y-90), a radioactive material that has been used previously in the treatment of liver tumors. Y-90 is incorporated into very tiny glass beads called microspheres and is injected into the liver through the blood vessels supplying the liver.

Official Title
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Phase II Study Of Intrahepatic Arterial Injection of 90-Y Glass Microspheres As First-Line Treatment For Cholangiocarcinoma

Conditions
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Cholangiocarcinoma

Intervention / Treatment
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* Device: TheraSphere® Yttrium-90 (Y-90) Microspheres


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have newly diagnosed or recurrent (post surgery) histologically or cytologically proven cholangiocarcinoma. Patients can have solitary, multifocal unilobar, or bilobar disease without evidence of extrahepatic involvement. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >10 mm with spiral computed tomography (CT) scan or magnetic resonance imaging (MRI). Age >18 years Life expectancy of greater than 3 months based on physician judgment Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2 (Karnofsky 50%) No prior chemotherapy or radiation treatment for cholangiocarcinoma Childs-Pugh score A or Childs-Pugh score B without portal vein thrombus Lung shunting that predicts lung dose to be <30 Gy in a single treatment The effects of TheraSpheres on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because radioactive spheres are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Ability to understand and the willingness to sign a written informed consent document Adequate baseline hematopoietic function: total white blood cell count equal to or greater than 3,000/mm³ absolute granulocyte count greater than 1,500/mm³ platelet count equal to or greater than 100,000/mm³ Hemoglobin >8.0 Exclusion Criteria: Patients receiving any other investigational agents Patients with extrahepatic disease Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because TheraSpheres are radioactive and radiation is a known agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TheraSpheres, breastfeeding should be discontinued if the mother is treated with TheraSpheres. Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. In addition, antiretrovirals are known radiation sensitizers and could dramatically increase the risk of fulminant hepatic failure. Therefore, HIV-positive patients are excluded from the study because of possible lethal side effects. Bulk disease (tumor volume > 70% of the target liver volume, or tumor nodules too numerous to count) Aspartic transaminase (AST) or alanine transaminase (ALT) > 5 times upper limit of normal (ULN) Bilirubin > 2 mg/dL Child-Pugh C Liver Cirrhosis Tumor volume > 50% combined with an albumin < 3 g/dL Complete occlusion of main portal vein causing portal hypertension

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arterial Injection of 90-Y Microspheres<br>Intrahepatic Arterial Injection of 90-Y Glass Microspheres as First-Line Treatment For Cholangiocarcinoma | Device: TheraSphere® Yttrium-90 (Y-90) Microspheres<br>* Y-90 is incorporated into very tiny glass beads called microspheres and is injected into the liver through the blood vessels supplying the liver.<br>* Other names: Yttrium Glass Microspheres;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Progression Free Survival (PFS) | PFS is defined as the duration of time from enrollment to time of progression or death from any cause. Progression will be defined as progressive disease in the treated lobe. If progression is seen in a treated lobe, this will be considered a treatment failure. Progressive Disease (PD) according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) Version 1.1.: At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | End of post treatment follow-up period of 20 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Overall Survival (OS) | OS is defined as the duration of time from enrollment to time of death from any cause. | Up to 36 months | 
| Overall Response Rate (ORR) | Tumor Response according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Complete Response (CR): Complete disappearance of all target and non-target lesions; no new lesions. Partial Response (PR): Applies only to patients with at least one measurable lesion; Greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions; No unequivocal progression of non-measurable disease; No new lesions. | End of post treatment follow-up period of up to 20 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver, Bile Duct