Yttrium-90 Radioembolization for Cirrhosis-Associated Thrombocytopenia

Not Applicable

Terminated

Conditions: Thrombocytopenia
Cirrhosis

Interventions: Device: TheraSphere® Yttrium-90 Glass Microspheres, BTG International Inc.

Registration Number: NCT03059030

Lead Sponsor: Northwestern University

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

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 20

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Subjects with thrombocytopenia secondary to cirrhosis	TheraSphere® Yttrium-90 Glass Microspheres, BTG International Inc.	Evaluate the safety and efficacy of 90Y radioembolization for the management of thrombocytopenia.

Primary Outcome Measures

Name	Time	Method
The Primary Objective of This Pilot Study is to Evaluate the Safety of 90Y TARE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. Evaluation of Overall AE Reporting in All Categories.	6 months	The number and the severity of ALL adverse events will be recorded to evaluate safety. Events will be reported by subjects at follow up visits. Scale: Common Terminology Criteria for Adverse Events (CTCAE) CT CAE v 4.0.3 Grades range from 1-5 with 5 being the worst (Death), descriptions of each grade for specific AE's are available here: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf Total AE's of different types are collected and for each grade are reported as a group
Safety of 90Y RE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. Reporting of Splenic Abscess.	6 months	The number and the severity of adverse events related to splenic abscess will be recorded to evaluate safety. Events will be reported by subjects at follow up visits. Scale: Common Terminology Criteria for Adverse Events (CTCAE) CT CAE v 4.0.3 Grades range from 1-5 with 5 being the worst (Death), Grade 1 (Mild):Small abscess with minimal symptoms, often not requiring intervention. Grade 2 (Moderate):Larger abscess causing moderate symptoms, may require antibiotics or drainage procedures. Grade 3 (Severe):Large abscess with significant symptoms, potentially causing systemic effects, requiring hospitalization and aggressive management. Grade 4 (Life-threatening):Abscess with immediate life-threatening complications, requiring urgent intervention. Grade 5 Death
Safety of 90Y RE for the Treatment of Thrombocytopenia in the Setting of Cirrhosis. AE's Related to Infection.	6 months	The number and the severity of adverse events related to infection will be recorded to evaluate safety. Events will be reported by subjects at follow up visits. Common Terminology Criteria for Adverse Events (CTCAE) CT CAE v 4.0.3, Grades range from 1-5 with 5 being the worst (Death) Grade 1 (Mild): Asymptomatic or mild symptoms, only requiring clinical observation, no intervention needed. Grade 2 (Moderate): Symptoms limiting some daily activities, minimal intervention may be required. Grade 3 (Severe): Symptoms significantly impacting self-care, requiring hospitalization or prolonged stay. Grade 4 (Life-threatening): Urgent intervention needed due to life-threatening complications. Grade 5 (Death): Death directly related to the infection.
Asses the Need for Technetium Albumin Aggregated (TC-MAA 99m) Injection to Determine Shunting Prior to Y90 Administration	6 months	MAA injection will be done and nuclear medicine PET scan to evaluate shunting and evaluated for the first 4 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.

Secondary Outcome Measures

Name	Time	Method
Achieve a 50% Increase in Platelet Count Six Months After Therapy.	6 months	Complete Blood Count with platelets will be drawn at baseline, treatment, 2, 4, 6, 8 weeks and 3, 4, 5, 6 months post treatment. Comparison made with screening platelet count and 6 month follow up visit platelet count.
Achieve 20% Decrease in Functional Splenic Volume Six Months After Treatment	6 months	Assessed via cross sectional CT or MR of the abdomen at screening and at 4 weeks, 3 months, and 6 months post treatment. Comparison made with screening CT or MR and 6 month follow up imaging.
Evaluate Length of Hospital Stay After Procedure	6 months	Determine the average length of stay in the hospital in days after treatment.