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Pembrolizumab Plus Y90 Radioembolization in HCC Subjects

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ClinicalTrials.gov Identifier: NCT03099564
Recruitment Status : Recruiting
First Posted : April 4, 2017
Last Update Posted : April 3, 2019
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Hoosier Cancer Research Network
Information provided by (Responsible Party):
Autumn McRee, MD, Hoosier Cancer Research Network

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.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: Pembrolizumab Device: Y90 radioembolization Early Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Pembrolizumab in Combination With Y90 Radioembolization in Subjects With Poor Prognosis Hepatocellular Carcinoma With Preserved Liver Function. HCRN: GI15-225
Actual Study Start Date : March 28, 2017
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: pembrolizumab + Y90 radioembolization
Pembrolizumab 200mg IV every 3 weeks in conjunction with Y90 radioembolization (performed one week after the first dose of pembrolizumab)
Drug: Pembrolizumab
pembrolizumab 200mg IV every three weeks
Other Name: Keytruda®

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).




Primary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: 6 months ]
    Freedom from progression or death at 6 months based on RECIST 1.1 criteria


Secondary Outcome Measures :
  1. Assess Safety - toxicities as defined by the NCI CTCAE v4 [ Time Frame: 2 years ]
    Grade 3 and 4 toxicities as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v4

  2. Time to progression (TTP) [ Time Frame: 2 years ]
    Time from Day 1 (D1) of pembrolizumab to progression

  3. Objective response rate (ORR) [ Time Frame: 2 years ]
    Per RECIST1.1 and mRECIST for Hepatocellular Carcinoma (HCC) and will be calculated as the number of subjects with a Complete Response (CR) or Partial Response (PR) divided by the total number of evaluable subjects

  4. Estimate overall survival (OS) [ Time Frame: 3 years ]
    The time from Day 1 (D1) of pembrolizumab to death from any cause



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • All disease must be amenable to embolization in one or two procedures
  • Childs-Pugh Cirrhotic Status A or B with a maximum score of 7
  • No evidence of clinically apparent ascites or active encephalopathy, and/or varices that have not been treated. Subjects with controlled ascites or encephalopathy are eligible so long as they meet Childs-Pugh score criterion. Please note that controlled ascites and encephalopathy require scores of 2 each when calculating the C-P score.
  • No prior systemic therapy or radiotherapy (including Y90 radioembolization or cyberknife) for HCC. No prior TAE or TACE allowed. Previous liver resection and ablation therapy is permitted. Allowed prior therapies must be completed 4 weeks prior to the baseline scan, and untreated measurable disease (as per RECIST1.1) must be present.
  • Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to registration:

Hematological:

Absolute Neutrophil Count (ANC) ≥ 1.5 x 10^9/L; Hemoglobin (Hgb) ≥ 9 g/dL; Platelet Count ≥ 60 x 10^9/L

Renal:

Calculated creatinine clearance ≥ 60 cc/min

Hepatic:

Bilirubin < 2.0 X ULN; Aspartate aminotransferase (AST) ≤ 5 × ULN; Alanine aminotransferase (ALT) ≤ 5 × ULN

Coagulation:

International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5

  • Females of childbearing potential must have a negative serum pregnancy test within 72 hours prior to registration.
  • Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use effective methods of contraception from the time of informed consent until 120 days after treatment discontinuation.
  • Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
  • Is willing to undergo a mandatory pre-treatment (all subjects) and post-treatment (10 subjects) research biopsy at the centers participating in research biopsies

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
  • Vascular abnormalities or bleeding diathesis that indicates hepatic artery catheterization is contraindicated
  • Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody
  • Known history of HIV
  • Untreated active HBV
  • Dual infection with HBV/HCV or other hepatitis combinations at study entry
  • Known history of, or any evidence of active, non-infectious pneumonitis
  • History of organ or stem cell transplantation including previous history of liver transplantation
  • Active infection requiring systemic therapy
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • Has history or current evidence of any condition, therapy or laboratory abnormality that may confound results or interfere with subject's participation in the trial.
  • Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least three years.
  • Has received a live vaccine within 30 days of planned start of study therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03099564


Contacts
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Contact: Ahran Lee 317.634.5842 ext 14 alee@hoosiercancer.org
Contact: Autumn McRee, MD 919.966.5902 autumn_mcree@med.unc.edu

Locations
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United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Janet Flynn    317-274-0972    janflynn@iupui.edu   
Principal Investigator: Safi Shahda, MD         
United States, North Carolina
The University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599-7097
Contact: Autumn McRee, M.D.    919-966-5902    autumn_mcree@med.unc.edu   
United States, Washington
University of Washington/Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Contact: Vivian Nguyen    206-288-7614    vnguyen@seattlecca.org   
Principal Investigator: William Harris, MD         
Sponsors and Collaborators
Autumn McRee, MD
Merck Sharp & Dohme Corp.
Hoosier Cancer Research Network
Investigators
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Study Chair: Autumn McRee, MD Hoosier Cancer Research Network

Additional Information:
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Responsible Party: Autumn McRee, MD, Sponsor-Investigator, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT03099564     History of Changes
Other Study ID Numbers: HCRN GI15-225
First Posted: April 4, 2017    Key Record Dates
Last Update Posted: April 3, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Autumn McRee, MD, Hoosier Cancer Research Network:
Pembrolizumab
Y90 Radioembolization
KEYTRUDA®
TheraSphere®
PD-1
IgG4/kappa isotype

Additional relevant MeSH terms:
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Pembrolizumab
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents