Clinical Trials /

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

NCT03211416

Description:

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.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Sorafenib Tosylate and Pembrolizumab in Treating Patients With Advanced or Metastatic Liver Cancer
  • Official Title: A Phase Ib/ II Study of Sorafenib and Pembrolizumab in Advanced Hepatocellular Cancer (HCC)

Clinical Trial IDs

  • ORG STUDY ID: I 35316
  • SECONDARY ID: NCI-2017-01114
  • SECONDARY ID: I 35316
  • SECONDARY ID: P30CA016056
  • NCT ID: NCT03211416

Conditions

  • 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

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (sorafenib tosylate, pembrolizumab)
Sorafenib TosylateBAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenibTreatment (sorafenib tosylate, pembrolizumab)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (sorafenib tosylate, pembrolizumab)ExperimentalPatients 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.
  • Pembrolizumab
  • Sorafenib Tosylate

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate defined as partial or complete response per immune-related Response Evaluation Criteria in Solid Tumors
Time Frame:Up to 6 months
Safety Issue:
Description: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

Measure:Overall survival
Time Frame:From the date of study enrollment to the time of death from any cause, assessed up to 1 year
Safety Issue:
Description:Will be estimated using the Kaplan-Meier method.
Measure:Time to tumor progression
Time Frame:From the date of study enrollment to the first observation of progressive disease, assessed up to 1 year
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Roswell Park Cancer Institute

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