NCT03099564

Pembrolizumab Plus Y90 Radioembolization in HCC Subjects

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

• Status: Unknown
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Ashwin Somasundaram · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Hepatocellular Carcinoma

Interventions

Type	Name	Description
DRUG	Pembrolizumab	pembrolizumab 200mg IV every three weeks
DEVICE	Y90 radioembolization	The first Y90 radioembolization treatment will be administered one week after the first dose of pembrolizumab. 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).

Timeline

• Start date: 2017-03-28
• Primary completion: 2021-05-19
• Completion: 2023-06-01
• First posted: 2017-04-04
• Last updated: 2023-02-06

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study