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A Study of Pembrolizumab and Bavituximab in Patients With Advanced Hepatocellular Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03519997
Recruitment Status : Recruiting
First Posted : May 9, 2018
Last Update Posted : May 1, 2023
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
David Hsieh, University of Texas Southwestern Medical Center

Brief Summary:
This is a non-randomized, open-label, multi-site phase II therapeutic trial of pembrolizumab and bavituximab in patients with locally advanced HCC. Locally advanced or metastatic HCC is defined as disease that is not amenable to surgical and/or locoregional therapies. Subjects must not have received prior systemic therapy for advanced HCC in keeping with the first-line setting of this study.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: Pembrolizumab Drug: Bavituximab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Locally advanced or metastatic HCC not amenable to locoregional therapy
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Pembrolizumab and Bavituximab in Patients With Advanced Hepatocellular Carcinoma
Actual Study Start Date : April 26, 2018
Estimated Primary Completion Date : April 1, 2024
Estimated Study Completion Date : April 1, 2025

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Pembro + Bavi
Pembrolizumab 200 mg IV every 3 weeks plus, Bavituximab 3mg/kg IV weekly
Drug: Pembrolizumab
Pembroluzumab 200mg IV once every 3 weeks

Drug: Bavituximab
Bavituximab 3mg/kg IV weekly

Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: 36 months ]
    To determine the overall response rate (ORR) of combination pembrolizumab and bavituximab in patients with advanced HCC.

Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 36 months ]
    To determine overall survival, 6-month progression free survival, and duration of response of combination pembrolizumab and bavituximab compared to historical controls

  2. Safety and Tolerability: rates of adverse events according to the CTCAE [ Time Frame: 36 months ]
    To determine the safety and tolerability of combination pembrolizumab and bavituximab as measured by rates of adverse events according to the CTCAE

Other Outcome Measures:
  1. Treatment response [ Time Frame: 36 months ]
    To determine treatment response with pre- and intra-treatment biopsies and plasma/serum. Correlative studies will be performed on the collected tissue and blood samples to determine if predictive markers of response can be generated

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patient must have a histologically confirmed diagnosis hepatocellular carcinoma; known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC will be excluded
  • Locally advanced or metastatic disease
  • Patients with locally advanced or metastatic disease must have disease deemed not amenable to surgical and/or locoregional therapies or patients who have progressed following surgical and/or locoregional therapies.
  • Measurable disease, as defined as lesions that can accurately be measured in at least one dimension according to RECIST version 1.1 at least 1 cm with contrast enhanced dynamic imaging (magnetic resonance imaging or computed tomography).
  • Child-Pugh Score A
  • Age ≥ 18 years
  • ECOG Performance score of 0-1
  • Life expectancy greater than 6 months
  • Following baseline laboratory values:

    1. Total bilirubin ≤ 2.0 mg/ml
    2. INR ≤ 1.7
    3. Hgb ≥ 8.5 g/dl
    4. AST, ALT ≤5 times ULN
    5. Platelet count ≥ 50,000/mm3
    6. Serum creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 50 mL/min
    7. Albumin ≥ 2.5 g/dl
    8. Absolute neutrophil ≥ 1,500 cells/mm3
  • Male and female subjects of child bearing potential must agree to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication
  • Women of childbearing potential must have a negative pregnancy test within 72 hours prior to receiving the first dose of study medication
  • Subjects are eligible to enroll if they have non-viral-HCC, or if they have HBV-HCC, or HCV-HCC defined as follows:

HBV-HCC: Controlled (treated) hepatitis B subjects will be allowed if they meet the following criteria:

Antiviral therapy for HBV must be given for at least 12 weeks and HBV viral load must be less than 100 IU/mL prior to first dose of study drug. Subjects on active HBV therapy with viral loads under 100 IU/ml should stay on the same therapy throughout study treatment.

Subjects who are anti-HBc (+), negative for HBsAg, negative for anti-HBs, and have an HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis.

HCV-HCC: active or resolved HCV infection as evidenced by detectable HCV RNA or antibody. Patients who have failed HCV therapy as evidenced by detectable HCV RNA will be eligible. Subjects with chronic infection by HCV who are treated (successfully or treatment failure) or untreated are allowed on study. In addition, subjects with successful HCV treatment are allowed as long as there are ≥4 weeks between completion of HCV therapy and start of study drug.

Successful HCV treatment definition: SVR12.

- Prior therapy is allowed provided the following are met: at least 4 weeks since prior locoregional therapy including surgical resection, chemoembolization, radiotherapy, or ablation. Provided target lesion has increased in size by 25% or more or the target lesion was not treated with locoregional therapy. Patients treated with palliative radiotherapy for symptoms will be eligible 1 week after treatment as long as the target lesion is not the treated lesion.

Exclusion Criteria:

  • Prior liver transplant;
  • Patient who has received previous systemic therapy for HCC;
  • Clinically significant, uncontrolled heart disease and/or recent events including any of the following:
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening;
  • History of documented congestive heart failure (New York Heart Association functional classification III-IV);
  • Documented cardiomyopathy;
  • Patient has a left ventricular ejection fraction <40% as determined by MUGA scan or ECHO (MUGA and ECHO are not required prior to enrollment);
  • Known human immunodeficiency virus (HIV) positive (testing not required);
  • History of thromboembolic events (including both pulmonary embolism and deep venous thrombus but not including tumor thrombus) within the last 6 months;
  • Hypersensitivity to IV contrast; not suitable for pre-medication;
  • Active or fungal infections requiring systemic treatment within 7 days prior to screening;
  • Known history of, or any evidence of, interstitial lung disease or active non-infectious pneumonitis;
  • Evidence of poorly controlled hypertension which is defined as systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg despite optimal medical management;
  • Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication;
  • Active, known, or suspected autoimmune disease with the following exceptions i) Subjects with vitiligo, type I diabetes mellitus, resolved childhood asthma or atopy are permitted to enroll; ii) Subjects with suspected autoimmune thyroid disorders may be enrolled if they are currently euthyroid or with residual hypothyroidism requiring only hormone replacement.

iii) Subjects with psoriasis requiring systemic therapy must be excluded from enrollment

  • Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the study or compromise compliance with the protocol (e.g. chronic pancreatitis, active untreated or uncontrolled fungal, bacterial, or viral infections, etc.);
  • Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the study or compromise compliance with the protocol (e.g. chronic pancreatitis, active untreated or uncontrolled fungal, bacterial, or viral infections, etc.);
  • Known history of active bacillus tuberculosis;
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days of study administration. Inhaled or topical steroids and adrenal replacement doses >10 mg/day prednisone equivalents are permitted in the absence of autoimmune disease;
  • Patient who has received radiotherapy ≤ 4 weeks prior to study entry. Palliative radiotherapy for symptomatic control is acceptable (if completed at least 2 weeks prior to study drug administration and no additional radiotherapy for the same lesion is planned);
  • Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery);
  • Clinically apparent ascites on physical examination, ascites present on imaging studies is allowed;
  • Patient has a known hypersensitivity to any of the excipients of bavituximab or pembrolizumab or monoclonal antibody;
  • Active gastrointestinal bleeding within previous 2 months;
  • History of any condition requiring anti-platelet therapy (aspirin >300 mg/day, clopidogrel >75 mg/day);
  • Prisoners or subjects who are involuntarily incarcerated;
  • Symptomatic or clinically active brain metastases;
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after contraception and until the termination of gestation, confirmed by a positive hCG laboratory test;
  • Prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2 agents;
  • Has dual active HBV infection (HBsAg (+) and /or detectable HBV DNA) and HCV infection (anti-HCV Ab(+) and detectable HCV RNA) at study entry.

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 identifier (NCT number): NCT03519997

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Contact: Ellen Siglinsky 214-648-7031

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United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Ellen Siglinsky    214-648-7031   
Sponsors and Collaborators
David Hsieh
Merck Sharp & Dohme LLC
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Principal Investigator: David Hsieh, MD UT Southwestern Medical Center
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Responsible Party: David Hsieh, ASSISTANT PROFESSOR- Internal Medicine - IM-Hem Onc, University of Texas Southwestern Medical Center Identifier: NCT03519997    
Other Study ID Numbers: STU 102017-015
First Posted: May 9, 2018    Key Record Dates
Last Update Posted: May 1, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action