Clinical trial NCT03347292: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Hepatocellular
Keywords: Liver cell carcinoma
Liver cancer
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-11-20
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Incidence of treatment-emergent adverse event(TEAEs)
timeFrame: Up to 30 days after last dose of study drug
measure: Severity of TEAEs
timeFrame: Up to 30 days after last dose of study drug
measure: Dose Limiting Toxicities(DLTs)
timeFrame: Up to 42 days after first treatment administration
Secondary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: After approximately 18 months
measure: Progression-free survival (PFS)
timeFrame: After approximately 36 months
measure: Time to progression (TTP)
timeFrame: After approximately 36 months
measure: Overall survival (OS)
timeFrame: After approximately 36 months
measure: Overall response rate (ORR)
timeFrame: After approximately 36 months
measure: Disease control rate (DCR)
timeFrame: After approximately 36 months
measure: Duration of response (DOR)
timeFrame: After approximately 36 months
measure: Duration of stable disease
timeFrame: After approximately 36 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Hospital and Clinics
state: California
city: Gainesville
country: United States
facility: University of Florida Health Sciences Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Köln
country: Germany
facility: Universitätsklinikum Köln
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg Universität Mainz
state: Rheinland-Pfalz
Study officials:
References: