Yttrium-90 Radioembolization for Cirrhosis-Associated Thrombocytopenia

Study Overview
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Brief Summary
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Evaluate the safety and efficacy of Yttrium-90 (90Y) radioembolization for the management of thrombocytopenia.

Detailed Description
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This protocol will provide access to TheraSphere® treatment for patients who have refractory thrombocytopenia secondary to cirrhosis. This protocol will utilize splenic artery-directed TheraSphere® treatment.

Official Title
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Yttrium-90 Radioembolization for Cirrhosis-Associated Thrombocytopenia

Conditions
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Thrombocytopenia, Cirrhosis

Intervention / Treatment
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* Device: TheraSphere® Yttrium-90 Glass Microspheres, BTG International Inc.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 years of age or older, of any ethnic or racial group. Diagnosis of cirrhosis or portal hypertension with a serum platelet count less than or equal to 80 × 109/L. [Rationale: platelet count <100 × 109/L triples the rate of liver-related adverse events (3) and worsens postoperative survival in the setting of hepatocellular carcinoma (HCC) (4). Initial platelet count of 80 × 109/L can allow the majority of patients who successfully respond to 90Y-RE (clinical endpoint of 50% platelet count increase) to exceed the 100 × 109/L threshold.] Cirrhosis is defined by one of three criteria: Liver Biopsy/histology consistent with cirrhotic architectural liver changes Portal hypertension (Hepatic venous pressure gradient ≥10 mm Hg) Evidence of esophageal and/or gastric varices Patients must have evidence of splenomegaly as determined by screening cross-sectional imaging. No evidence of myelosuppression (e.g. lymphopenia) as evidenced by normal hematology values at Screening Adequate baseline organ function(with the exception of cirrhosis) as evidenced by normal BUN/Cr and electrolytes on screening chemistry. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2 Patient has a life expectancy of greater than 6 months without intervention. Patient is willing to participate in the study and has signed the study informed consent. Women of childbearing potential must have a negative serum pregnancy test within 28 days prior to screening and must not be breastfeeding. Exclusion Criteria: Patients with serum platelet count less than 10 × 109/L. History of bleeding disorder attributed to another cause other than cirrhosis (e.g. Von Willebrand disease) Declines or unable to provide informed consent History of prior partial splenic embolization (PSE) or splenectomy Use of any medication known to increase platelet count 1 month prior to Baseline. History of allergy or sensitivity to TheraSphere® or its components. History of severe peripheral allergy or intolerance to contrast agents, narcotics, sedatives or atropine that cannot be managed medically Contraindications to angiography and selective visceral catheterization such as bleeding, diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents (e.g. closure device) Previous randomization in a trial using 90Y RE Patient must not have participated or enrolled in a clinical trial with an investigational device / therapy within 30 days prior to randomization Any serious medical condition likely to impede successful completion of the study, such as certain mental disorders, cardiac arrhythmias, and uncontrolled congestive heart failure or respiratory disease. Patients actively on chemotherapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Subjects with thrombocytopenia secondary to cirrhosis<br>Evaluate the safety and efficacy of 90Y radioembolization for the management of thrombocytopenia. | Device: TheraSphere® Yttrium-90 Glass Microspheres, BTG International Inc.<br>* The Interventional Radiologists will inject a dose of Yttrium 90 into your spleen through a small catheter placed in your femoral artery.The entire treatment visit is an outpatient procedure. You will only be admitted to the hospital if the physician deems it necessary due to any symptoms you may experience after the treatment is given. This visit may take 6 to 8 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of 90Y Radioembolization (RE) for the treatment of thrombocytopenia in the setting of cirrhosis, evaluated by the number of participants with treatment-related adverse events as assessed by CTCAE v4.0. | Assess for infection after Y90 treatment to the spleen by physical exam noted by a change in vital signs and lab values such as white blood count at each follow up visit. | 6 months | 
| Safety of 90Y RE for the treatment of thrombocytopenia in the setting of cirrhosis. | Assess for splenic abscess after Y90 to the spleen as seen on follow up CT imaging at 1, 3, and 6 months post treatment. This will also be evaluated at all visits by physical exam, fever, pain, and lab work. Visits occur at 2, 4, 6, 8 weeks, 3, 4, 5, 6 months. | 6 months | 
| Safety of 90Y RE for the treatment of thrombocytopenia in the setting of cirrhosis. | Assess for any adverse events after Y90 administration at follow visits or outside visits if they occur by physical exam and lab values at baseline, 2, 4, 6, 8 weeks, 3, 4, 5, 6 months post treatment. Lab value changes, ascites, fatigue, fever, nausea, dyspepsia, abdominal pain, pleural effusion, GI ulcer, pneumonitis, and thromboembolic events will be followed closely. | 6 months | 
| Asses the need for Technetium albumin aggregated (TC-MAA 99m) injection to determine shunting prior to Y90 administration | MAA injection will be done and nuclear medicine PET scan to evaluate shunting and evaluated for the first 5 patients. If shunt is <5% subsequently enrolled patients will not undergo MAA, if shunt is >5% all subsequent patients will undergo MAA. This will be evaluated post MAA injection before Y90 treatment. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate platelet count 6 months after treatment | Complete Blood Count with platelets will be drawn at baseline, treatment, 2, 4, 6, 8 weeks and 3, 4, 5, 6 months post treatment | 6 months | 
| Evaluate splenic volume post procedure | CT or MR of the abdomen will be done at screening, 4 weeks, 3 months, and 6 months after Y90 administration | 6 months | 
| Evaluate length of hospital stay after procedure | Length of stay in days will be recorded post procedure | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombocytopenia, cirrhosis, Therasphere®, Y90, Radioembolization