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Sorafenib Tosylate and Pembrolizumab in Treating Patients With Advanced or Metastatic Liver Cancer

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ClinicalTrials.gov Identifier: NCT03211416
Recruitment Status : Recruiting
First Posted : July 7, 2017
Last Update Posted : May 3, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Brief Summary:
This phase Ib/II trial studies how well sorafenib tosylate and pembrolizumab work in treating patients with liver cancer that has spread to other parts of the body. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving sorafenib tosylate and pembrolizumab may work better in treating patients with liver cancer.

Condition or disease Intervention/treatment Phase
Advanced Adult Hepatocellular Carcinoma Child-Pugh Class A Stage III Hepatocellular Carcinoma Stage IIIA Hepatocellular Carcinoma Stage IIIB Hepatocellular Carcinoma Stage IIIC Hepatocellular Carcinoma Stage IV Hepatocellular Carcinoma Stage IVA Hepatocellular Carcinoma Stage IVB Hepatocellular Carcinoma Other: Laboratory Biomarker Analysis Biological: Pembrolizumab Drug: Sorafenib Tosylate Phase 1 Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the overall response rate (ORR) related to the combination of sorafenib tosylate (sorafenib) + pembrolizumab in advanced hepatocellular carcinoma patients.

SECONDARY OBJECTIVES:

I. To assess time to tumor progression in patients who received the combination therapy of sorafenib + pembrolizumab compared to historical data on sorafenib only treatment in patients with advanced hepatocellular carcinoma.

TERTIARY OBJECTIVES:

I. To obtain data on changes in immune cell function and in the tumor microenvironment pre- and post-treatment to screen for potential biomarkers that may be able to predict clinical benefit.

- All patients will be followed for survival

OUTLINE:

Patients receive sorafenib tosylate orally (PO) twice daily (BID) on days -28 to -1 and 1-21. Patients also receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 3 months for up to 1 year, then every 6 months thereafter.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/ II Study of Sorafenib and Pembrolizumab in Advanced Hepatocellular Cancer (HCC)
Actual Study Start Date : September 13, 2017
Estimated Primary Completion Date : September 11, 2019
Estimated Study Completion Date : September 11, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer

Arm Intervention/treatment
Experimental: Treatment (sorafenib tosylate, pembrolizumab)
Patients receive sorafenib tosylate PO BID on days -28 to -1 and 1-21. Patients also receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Drug: Sorafenib Tosylate
Given PO
Other Names:
  • BAY 43-9006 Tosylate
  • BAY 54-9085
  • Nexavar
  • sorafenib




Primary Outcome Measures :
  1. Overall response rate defined as partial or complete response per immune-related Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 6 months ]
    The response rate will be estimated as the binomial proportion of responders among evaluable patients, and supported by Jeffreys? 95% confidence interval.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: From the date of study enrollment to the time of death from any cause, assessed up to 1 year ]
    Will be estimated using the Kaplan-Meier method.

  2. Time to tumor progression [ Time Frame: From the date of study enrollment to the first observation of progressive disease, assessed up to 1 year ]
    Will be estimated using the Kaplan-Meier method. Statistics describing the time to event distributions will be obtained from Kaplan-Meier methods and proportional hazards models. Continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with subgroup associations tested using the Wilcoxon rank sum test. Categorical variables will be summarized in contingency tables, with associations of interest assessed using Fisher?s exact test.


Other Outcome Measures:
  1. Change in functional activity of effector T cells [ Time Frame: Up to 1 year ]
    Will be correlated with overall survival. Measurements for several immune parameters will be obtained before and after treatment. The effect of treatment will be quantified as the post/pre-treatment mean ratio of the (potentially log transformed) expression measurements. Primary and derived immune marker expression measurements will be summarized with common descriptive statistics (mean/standard deviation). Associations between the paired pre- and post-measurements will be described with scatterplots and dot plots. The null hypothesis of no difference in the paired pre- and post-treatment meas

  2. Change in levels of immunosuppressive cells [ Time Frame: Up to 1 year ]
    Will be correlated with overall survival. Measurements for several immune parameters will be obtained before and after treatment. The effect of treatment will be quantified as the post/pre-treatment mean ratio of the (potentially log transformed) expression measurements. Primary and derived immune marker expression measurements will be summarized with common descriptive statistics (mean/standard deviation). Associations between the paired pre- and post-measurements will be described with scatterplots and dot plots. The null hypothesis of no difference in the paired pre- and post-treatment mea



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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:

  • Participant must have histologically confirmed hepatocellular cancer (HCC) that is advanced or metastatic and have archival tissue available for PD-L1, PD-L2 testing
  • Participants with measurable disease that has progressed are eligible if prior surgery or locoregional therapy occurred > 28 days prior to enrollment
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky >= 60%)
  • Child-Pugh class-A liver function
  • Absolute neutrophil count (ANC) >= 1,500/ mcL
  • Hemoglobin >= 8.5 g/dL
  • Platelets >= 75,000/ mcL
  • Serum total bilirubin =< 2.0 mg/dL
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 X ULN
  • Serum Creatinine <= 1.5 upper limit of normal (ULN)or Creatinine clearance > 50 mL/minute if serum creatinine is elevated above 1.5 X ULN
  • Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present
  • Ability to swallow and retain oral medication
  • Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
  • Participants with past or ongoing hepatitis C virus (HCV) infection will be eligible for the study. The treated participants must have completed their treatment at least 1 month prior to starting study intervention.
  • Participants with controlled hepatitis B will be eligible as long as 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. Participants on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study treatment Participants who are anti-HBc , negative for Hepatitis B surface antigen (HBsAg) and negative or positive for anti-HBs, and who have an HBV viral load under 100 IU/mL , do not require HBV anti-viral prophylaxis

Exclusion Criteria:

  • Participants who have received prior sorafenib or anti-PD1 therapy for HCC
  • Participants who have had radiotherapy or chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Any evidence of bleeding diathesis (patients on therapeutic warfarin or heparin will be excluded)
  • Participants with a history of variceal bleed within 6 months prior to enrollment
  • Known human immunodeficiency virus (HIV)-positive participants (even if on combination retrovirals, participant will be excluded
  • Participants with chronic autoimmune disease
  • Participants with known brain metastases should be excluded from this clinical trial
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Has known history of, or any evidence of active, non-infectious pneumonitis
  • Pregnant or nursing female participants
  • Unwilling or unable to follow protocol requirements
  • Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug
  • Received a live vaccine within 30 days prior to start of study treatment

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): NCT03211416


Locations
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United States, Illinois
Robert H Lurie Comprehensive Cancer Center Recruiting
Chicago, Illinois, United States, 60611
Contact: Sara Craig    312-695-1352    sarah.craig@northwestern.edu   
Principal Investigator: Devalingam Mahalingam, MD         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Roswell Park    877-275-7724    ASKRPCI@roswellpark.org   
Principal Investigator: Renuka V. Iyer         
Sponsors and Collaborators
Roswell Park Cancer Institute
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Renuka Iyer Roswell Park Cancer Institute

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Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT03211416     History of Changes
Other Study ID Numbers: I 35316
NCI-2017-01114 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 35316 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
First Posted: July 7, 2017    Key Record Dates
Last Update Posted: May 3, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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
Pembrolizumab
Sorafenib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action