Clinical Trials /

Regorafenib Plus Pembrolizumab in First Line Systemic Treatment of HCC

NCT03347292

Description:

This study will determine if the combination of regorafenib and pembrolizumab is safe and tolerated in patients with advanced liver cancer. In addition, the study will explore the anti-tumor activity of this combination as well as potentially identifying blood and tissue biomarkers associated with disease activity, status or response. The study will also investigate how the drugs behave in your body

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Regorafenib Plus Pembrolizumab in First Line Systemic Treatment of HCC
  • Official Title: A Multicenter, Non-randomized, Open-label Dose Escalation Phase Ib Study of Regorafenib in Combination With Pembrolizumab in Patients With Advanced Hepatocellular Carcinoma (HCC) With no Prior Systemic Therapy

Clinical Trial IDs

  • ORG STUDY ID: 19497
  • SECONDARY ID: KN-743
  • SECONDARY ID: 2017-003202-40
  • NCT ID: NCT03347292

Conditions

  • Carcinoma, Hepatocellular

Interventions

DrugSynonymsArms
Regorafenib(Stivarga, BAY73-4506)Dose escalation
PembrolizumabDose escalation

Purpose

This study will determine if the combination of regorafenib and pembrolizumab is safe and tolerated in patients with advanced liver cancer. In addition, the study will explore the anti-tumor activity of this combination as well as potentially identifying blood and tissue biomarkers associated with disease activity, status or response. The study will also investigate how the drugs behave in your body

Trial Arms

NameTypeDescriptionInterventions
Dose escalationExperimentalThe regorafenib starting dose will be 120 mg q.d.(once daily) 3 weeks on / 1 week off in combination with the recommended dose of pembrolizumab (200 mg Q3W). Pembrolizumab dose will not be escalated or de-escalated.
  • Regorafenib(Stivarga, BAY73-4506)
  • Pembrolizumab
Dose expansionExperimentalDose expansion cohorts will continue to be expanded until the sample size of 30 patients per cohort is reached.
  • Regorafenib(Stivarga, BAY73-4506)
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female patients ≥ 18 years of age on day of signing informed consent.

          -  Histological or cytological confirmation of HCC (hepatocellular carcinoma) or
             non-invasive diagnosis of HCC as per American Association for the Study of Liver
             Diseases (AASLD) criteria in patients with a confirmed diagnosis of cirrhosis.

          -  Barcelona Clinic Liver Cancer (BCLC) stage B or C that cannot benefit from treatments
             of established efficacy such as resection, local ablation, chemoembolization.

          -  Liver function status Child-Pugh (CP) Class A. CP status should be calculated based on
             clinical findings and laboratory results during the screening period.

          -  Any local or loco-regional therapy of intrahepatic tumor lesions (e.g. surgery,
             radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency
             ablation, percutaneous ethanol injection, or cryoablation) must have been completed ≥
             4 weeks before first dose of study medication. Note: patients who received sole
             intrahepatic intra-arterial chemotherapy, without lipiodol or embolizing agents are
             not eligible.

          -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.

          -  At least one uni-dimensional measurable lesion by computed tomography (CT) scan or
             magnetic resonance imaging (MRI) according to RECIST (RECIST version 1.1) and no older
             than 28 days before start of the study treatment. Tumor lesions situated in a
             previously irradiated area, or in an area subjected to other loco-regional therapy,
             may be considered measurable if there has been demonstrated progression in the lesion.

          -  Life expectancy of at least 3 months.

          -  Adequate bone marrow and organ function as assessed by the laboratory tests performed
             within 7 days before of treatment initiation.

          -  For patients recruited in the expansion cohort only, provision of archival (block) or
             fresh tumor tissue samples at baseline is mandatory. If archival tumor tissue is not
             available, patients should be willing to undergo a biopsy for provision of fresh tumor
             samples

        Exclusion Criteria:

          -  Prior systemic therapy for HCC; prior exposure to regorafenib.

          -  Previous treatment with a programmed death 1 (PD1), programmed death-ligand (PD-L1),
             or cytotoxicT-lymphocyte-associated protein 4 (CTLA-4) inhibitors, or any form of
             immunotherapy for HCC.

          -  Previous treatment with live vaccine within 30 days of planned start of study drugs
             (seasonal flu vaccines that do not contain a live virus are permitted).

          -  Active autoimmune disease (active defined as having autoimmune disease related
             symptoms and detectable autoantibodies) that has required systemic treatment in the
             past 2 years (i.e., with use of diseasemodifying agents, corticosteroids, or
             immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
             physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
             etc.) is not considered a form of systemic treatment.

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior to the first dose of study drugs. The
             use of physiologic doses of corticosteroids may be approved after consultation with
             the Sponsor.

          -  Known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibodies).

          -  Dual active HBV infection (HBsAg (+) and /or detectable HBV DNA) and HCV infection
             (anti-HCV Ab(+) and detectable HCV RNA) at study entry.

          -  Pleural effusion or ascites that causes respiratory compromise (≥ CTCAE Grade 2
             dyspnea).

          -  Known history of metastatic brain or meningeal tumors.

          -  Significant acute gastrointestinal disorders with diarrhea as a major symptom e.g.,
             Crohn's disease,malabsorption, or CTCAE Grade ≥ 2 diarrhea of any etiology.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of treatment-emergent adverse event(TEAEs)
Time Frame:Up to 30 days after last dose of study drug
Safety Issue:
Description:The incidence of treatment-emergent adverse events and treatment-emergent drug-related adverse events summarized in frequency tables using worst CTCAE v4.03 grade.

Secondary Outcome Measures

Measure:Maximum Tolerated Dose (MTD)
Time Frame:After approximately 18 months
Safety Issue:
Description:The MTD is defined as the highest dose that can be given so that toxicity probability is below the target toxicity PT =35%.
Measure:Progression-free survival (PFS)
Time Frame:After approximately 36 months
Safety Issue:
Description:
Measure:Time to progression (TTP)
Time Frame:After approximately 36 months
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:After approximately 36 months
Safety Issue:
Description:
Measure:Overall response rate (ORR)
Time Frame:After approximately 36 months
Safety Issue:
Description:
Measure:Disease control rate (DCR)
Time Frame:After approximately 36 months
Safety Issue:
Description:
Measure:Duration of response (DOR)
Time Frame:After approximately 36 months
Safety Issue:
Description:
Measure:Duration of stable disease
Time Frame:After approximately 36 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bayer

Trial Keywords

  • Liver cell carcinoma
  • Liver cancer

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