Regorafenib Plus Pembrolizumab in First Line Systemic Treatment of HCC

NCT ID: NCT03347292

Last Updated: 2023-07-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-18
• Study Completion Date: 2022-09-06

Brief Summary

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

Conditions

Carcinoma, Hepatocellular

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose escalation

The 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.

Group Type: EXPERIMENTAL

Regorafenib(Stivarga, BAY73-4506)

Intervention Type: DRUG

Regorafenib 80mg/120mg/160mg q.d., 3 weeks on / 1 week off + pembrolizumab 200mg i.v. every 3 weeks

Pembrolizumab

Intervention Type: DRUG

200 mg i.v.(Intravenous(ly)) every 3 weeks (Q3W). This dose will not be escalated or deescalated and the dosing schedule will not be changed

Dose expansion

Dose expansion cohorts will continue to be expanded until the sample size of 30-35 patients per cohort is reached.

Group Type: EXPERIMENTAL

Regorafenib(Stivarga, BAY73-4506)

Intervention Type: DRUG

Regorafenib 80mg/120mg/160mg q.d., 3 weeks on / 1 week off + pembrolizumab 200mg i.v. every 3 weeks

Pembrolizumab

Intervention Type: DRUG

200 mg i.v.(Intravenous(ly)) every 3 weeks (Q3W). This dose will not be escalated or deescalated and the dosing schedule will not be changed

Interventions

Regorafenib(Stivarga, BAY73-4506)

Regorafenib 80mg/120mg/160mg q.d., 3 weeks on / 1 week off + pembrolizumab 200mg i.v. every 3 weeks

Intervention Type: DRUG

Pembrolizumab

200 mg i.v.(Intravenous(ly)) every 3 weeks (Q3W). This dose will not be escalated or deescalated and the dosing schedule will not be changed

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

USC Norris Hospital and Clinics

Los Angeles, California, United States

University of Florida Health Sciences Center

Gainesville, Florida, United States

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Mount Sinai Medical Center

New York, New York, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Universitätsklinikum Köln

Cologne, North Rhine-Westphalia, Germany

Universitätsmedizin der Johannes Gutenberg Universität Mainz

Mainz, Rhineland-Palatinate, Germany

Countries

United States; Germany

Other Identifiers

KN-743

Identifier Type: OTHER

Identifier Source: secondary_id

2017-003202-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

19497

Identifier Type: -

Identifier Source: org_study_id