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

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.
 
ClinicalTrials.gov Identifier: NCT03211416
Recruitment Status : Recruiting
First Posted : July 7, 2017
Last Update Posted : February 20, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Tracking Information
First Submitted Date  ICMJE July 5, 2017
First Posted Date  ICMJE July 7, 2017
Last Update Posted Date February 20, 2020
Actual Study Start Date  ICMJE September 13, 2017
Estimated Primary Completion Date September 13, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 5, 2017)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 5, 2017)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 5, 2017)
  • 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
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Sorafenib Tosylate and Pembrolizumab in Treating Patients With Advanced or Metastatic Liver Cancer
Official Title  ICMJE A Phase Ib/ II Study of Sorafenib and Pembrolizumab in Advanced Hepatocellular Cancer (HCC)
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Other: Laboratory Biomarker Analysis
  • Biological: Pembrolizumab
  • Drug: Sorafenib Tosylate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 5, 2017)
27
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 13, 2021
Estimated Primary Completion Date September 13, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participant must have histologically or radiographically confirmed hepatocellular cancer (HCC) that is advanced or metastatic and if archival tissue is available, have archival tissue submitted 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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03211416
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Roswell Park Cancer Institute
Study Sponsor  ICMJE Roswell Park Cancer Institute
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Renuka Iyer Roswell Park Cancer Institute
PRS Account Roswell Park Cancer Institute
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP