Regorafenib Plus Pembrolizumab in First Line Systemic Treatment of HCC

Carcinoma, Hepatocellular Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT03347292
• Other study ID #: 19497
• Secondary ID: KN-7432017-00320
• Status: Completed
• Phase: Phase 1
• Start date: June 18, 2018
• Est. completion date: September 6, 2022

Study information

• Verified date: July 2023
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: September 6, 2022
• Est. primary completion date: December 17, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• Regorafenib(Stivarga, BAY73-4506)
Regorafenib 80mg/120mg/160mg q.d., 3 weeks on / 1 week off + pembrolizumab 200mg i.v. every 3 weeks
• 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

Locations

Country	Name	City	State
Germany	Universitätsklinikum Köln	Köln	Nordrhein-Westfalen
Germany	Universitätsmedizin der Johannes Gutenberg Universität Mainz	Mainz	Rheinland-Pfalz
United States	University of Florida Health Sciences Center	Gainesville	Florida
United States	USC Norris Hospital and Clinics	Los Angeles	California
United States	Mount Sinai Medical Center	New York	New York
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Bayer	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse event(TEAEs)	The incidence of treatment-emergent adverse events and treatment-emergent drug-related adverse events summarized in frequency tables using worst CTCAE v4.03 grade.	Up to 30 days after last dose of study drug
Primary	Severity of TEAEs		Up to 30 days after last dose of study drug
Primary	Dose Limiting Toxicities(DLTs)		Up to 42 days after first treatment administration
Secondary	Maximum Tolerated Dose (MTD)	The MTD is defined as the highest dose that can be given so that toxicity probability is below the target toxicity PT =35%.	After approximately 18 months
Secondary	Progression-free survival (PFS)		After approximately 36 months
Secondary	Time to progression (TTP)		After approximately 36 months
Secondary	Overall survival (OS)		After approximately 36 months
Secondary	Overall response rate (ORR)		After approximately 36 months
Secondary	Disease control rate (DCR)		After approximately 36 months
Secondary	Duration of response (DOR)		After approximately 36 months
Secondary	Duration of stable disease		After approximately 36 months