A Pilot Study of Pembrolizumab in Combination With Y90 Radioembolization in Subjects With Poor Prognosis Hepatocellular Carcinoma With Preserved Liver Function. HCRN: GI15-225

Ashwin Somasundaram3 sites in 1 country30 target enrollmentMarch 28, 2017

ConditionsHepatocellular Carcinoma

InterventionsPembrolizumab Y90 radioembolization

DrugsPembrolizumab

Overview

Phase: Early Phase 1
Intervention: Pembrolizumab
Conditions: Hepatocellular Carcinoma
Sponsor: Ashwin Somasundaram
Enrollment: 30
Locations: 3
Primary Endpoint: Progression free survival (PFS)
Status: Active, not recruiting
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open-label multi-center trial designed to evaluate the efficacy as well as the safety of combining pembrolizumab with Yttrium-90 (Y90) radioembolization in subjects with poor prognosis (high risk) HCC not eligible for liver transplant or surgical resection with well compensated liver function. Treatment will consist of pembrolizumab 200mg IV every 3 weeks in conjunction with Y90 radioembolization performed one week after the first dose of pembrolizumab. If bilobar disease is present, a second Y90 radioembolization will be performed no later than 4 weeks after the first procedure to the contralateral hepatic lobe.

Detailed Description

If a second Y90 radioembolization treatment is required for bilobar disease, this should occur within 4 weeks of the initial procedure (between Cycles 2 and 3 of pembrolizumab). The next dose of pembrolizumab should be separated from the Y90 radioembolization by at least one week. Imaging will be obtained every 9 weeks (after every 3 pembrolizumab treatment) to assess for tumor response and to evaluate for progression. Subjects will remain on treatment until documented tumor progression, unacceptable toxicity, study withdrawal or death. Screening Angiography (shunt study): During screening, subjects will undergo angiography using technetium-99-labeled macroaggregated albumin to detect any uptake outside the liver via measurement of hepatopulmonary shunting. Prior to the angiography, a local anesthetic (to numb the area prior to catheter insertion) and sedation will be administered to the subject, as per institutional standards. This procedure is standard of care for subjects prior to Y90 radioembolization, and will be performed per institutional site standards. Hepatopulmonary shunting must be \< 20% for subject to meet eligibility criteria. Subjects will undergo a mandatory tumor biopsy on the same day as the screening angiography. Prior to administration of the first dose of pembrolizumab (i.e., Day 1 of Cycle 1), repeat laboratory tests will be obtained to ensure subject still meets eligibility criteria. Pembrolizumab 200mg IV (IV over 30 minutes) every 3 weeks Day 1 per 21 day cycle (3 weeks). Prior to administration of subsequent pembrolizumab doses, the following criteria must be met: ALT and AST: * Among subjects with baseline (screening) ALT/AST \<2×ULN: ALT/AST \< 5×ULN * Among subjects with baseline (screening) ALT/AST ≥2×ULN: ALT/AST \< 3× the baseline level * ALT/AST ≤ 500 U/L regardless of baseline level Total bilirubin: * Among subjects with baseline levels \< 1.5 mg/dL: a value of \< 2.0 mg/dL * Among subjects with baseline levels that are ≥ 1.5 mg/dL: a value \< 2× the baseline level * Total bilirubin ≤ 3.0 mg/dL regardless of baseline level Y90 radioembolization will be performed as standard of care via institutional standards. To be eligible for Y90 radioembolization, the following criteria must be met: ALT and AST: * Among subjects with baseline (screening) ALT/AST \< 2×ULN: ALT/AST \< 5×ULN * Among subjects with baseline (screening) ALT/AST ≥ 2×ULN: ALT/AST \< 3× the baseline level * ALT/AST ≤ 500 U/L regardless of baseline level Total bilirubin: * Among subjects with baseline levels \< 1.5 mg/dL: a value of \< 2.0 mg/dL * Among subjects with baseline levels that are ≥ 1.5 mg/dL: a value \< 2× the baseline level * Total bilirubin ≤ 3.0 mg/dL regardless of baseline level In addition, any non-hepatic toxicities from the prior dose(s) of pembrolizumab must have resolved to Grade ≤ 2.

Registry

clinicaltrials.gov

Start Date

March 28, 2017

End Date

June 2023

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Ashwin Somasundaram

Responsible Party

Sponsor Investigator

Principal Investigator

Ashwin Somasundaram

Sponsor-Investigator

Hoosier Cancer Research Network

Eligibility Criteria

Inclusion Criteria

•Subject must meet all of the following applicable inclusion criteria to participate in this study:
•Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately
•ECOG Performance Status of 0-1
•Locally advanced HCC as defined by: 1) tissue diagnosis OR 2) alpha-fetoprotein (AFP) \> 400 ng/mL with compatible mass on contrast-enhanced imaging OR 3) compatible mass on dual phase CT or dynamic contrast enhanced MRI demonstrating both arterial hypervascularity and delayed washout
•Hepatopulmonary shunting \< 20% as documented via hepatic artery perfusion study
•No evidence of extrahepatic metastatic disease
•Subjects must be considered poor prognosis by the following parameters: 1) right or left portal vein involvement (NOTE: subjects with main portal vein involvement are excluded), 2) multi-focal disease (more than 3 tumors regardless of size) AND/OR 3) diffuse disease considered amenable to liver directed therapy.
•Subjects with chronic infection by HCV who are untreated or who failed previous therapies for HCV are allowed on study. In addition, subjects with successful HCV treatment (defined as sustained virologic response \[SVR\] 12 or SVR 24) are allowed as long as patients are not actively receiving anti-HCV treatment at the time of study enrollment. Investigators can stop anti-HCV treatment at their discretion prior to enrolling patients on study. .
•If active HBV, viral load must be \<100IU/mL; if active HBV, subjects must be on anti-viral medication for ≥ 3 months prior to study registration and remain on the same anti-viral regimen throughout study treatment. NOTE: those subjects who are positive for Hepatitis B core antibody (anti-HBc), negative for Hepatitis B surface antigen (HBsAg) and negative for Hepatitis B surface antibody (anti-HBs), and have an HBV viral load \<100 IU/mL do not require HBV anti-viral prophylaxis.
•Not eligible for surgical resection or liver transplant or have refused such procedures.

Exclusion Criteria

•Subjects meeting any of the criteria below may not participate in the study:
•Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of study registration
•Diagnosis of immunodeficiency or is receiving systemic steroid therapy (other than oral contraceptives) or any other form of immunosuppressive therapy within 7 days prior to registration.
•Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g.thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency.) is not considered a form of systemic treatment.
•Known history of active TB
•Hypersensitivity to pembrolizumab or any of its excipients
•Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to registration or who has not recovered (i.e., ≤ Grade 1 or baseline) from adverse events due to agents administered \> 4 weeks prior
•Has had prior chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to registration, or who has not recovered (i.e., (i.e., ≤ Grade 1 or baseline)) from AEs due to previously administered agents
•If had major surgery, subject must have recovered adequately from the toxicity and/or complications from the intervention prior to study registration
•Complete portal vein occlusion