Study of Mapatumumab in Combination With Sorafenib in Subjects With Advanced Hepatocellular Carcinoma

NCT ID: NCT01258608

Last Updated: 2018-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-08
• Study Completion Date: 2017-11-29

Brief Summary

Mapatumumab is a fully human, agonist monoclonal antibody that activates the cell death pathway in tumor cells by specifically binding to TRAIL-R1 with high affinity. Sorafenib, a multikinase inhibitor, is the standard of care for treatment of patients with advanced hepatocellular carcinoma (HCC). The mechanisms of sorafenib and mapatumumab action suggest that these agents could interact synergistically. This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of mapatumumab in combination with sorafenib in subjects with advanced hepatocellular carcinoma.

Conditions

Carcinoma, Hepatocellular

Keywords

advanced hepatocellular carcinoma; Mapatumumab; HGS1012; sorafenib

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Sorafenib plus mapatumumab

Mapatumumab 30 milligrams (mg)/kilogram (kg) intravenously on Day 1 of each cycle (i.e. every 21 days) plus sorafenib 400 mg orally twice daily continuously in each cycle until radiologic disease progression or unacceptable toxicity

Group Type: EXPERIMENTAL

Mapatumumab

Intervention Type: DRUG

Mapatumumab will be supplied as a lyophilized formulation in 10 mL vials containing 100 mg mapatumumab for intravenous infusion at the dose of 30 mg/kg.

Sorafenib

Intervention Type: DRUG

Sorafenib will be supplied as tablets, each containing 274 mg sorafenib tosylate, equivalent to 200 mg of sorafenib, to be administered 400 mg (2 x 200 mg tablets) orally twice daily.

Sorafenib plus Placebo

Placebo intravenously on Day 1 of each cycle (i.e. every 21 days) plus sorafenib 400 mg orally twice daily continuously in each cycle until radiologic disease progression or unacceptable toxicity

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Normal saline solution for intravenous infusion will be administered as placebo for mapatumumab

Sorafenib

Intervention Type: DRUG

Sorafenib will be supplied as tablets, each containing 274 mg sorafenib tosylate, equivalent to 200 mg of sorafenib, to be administered 400 mg (2 x 200 mg tablets) orally twice daily.

Interventions

Mapatumumab

Mapatumumab will be supplied as a lyophilized formulation in 10 mL vials containing 100 mg mapatumumab for intravenous infusion at the dose of 30 mg/kg.

Intervention Type: DRUG

Placebo

Normal saline solution for intravenous infusion will be administered as placebo for mapatumumab

Intervention Type: DRUG

Sorafenib

Sorafenib will be supplied as tablets, each containing 274 mg sorafenib tosylate, equivalent to 200 mg of sorafenib, to be administered 400 mg (2 x 200 mg tablets) orally twice daily.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Child-Pugh Class A.
• Barcelona Clinic Liver Cancer (BCLC) advanced stage (C) hepatocellular carcinoma, or BCLC intermediate stage (B) hepatocellular carcinoma if treatment with transarterial chemoembolization is not considered appropriate
• Measurable disease demonstrating intratumoral arterial enhancement by contrast enhanced computerized tomography (CT), with use of multislice scanners, or contrast enhanced dynamic magnetic resonance imaging (MRI), with at least 1 tumor lesion that meets the following criteria: located in the liver; can be accurately measured in at least 1 dimension; well delineated area of viable, hypervascular (contrast enhancement in the arterial phase) tumor that is >2 centimeter (cm) in the axial plane; suitable for repeat measurement; OR not previously treated with locoregional or systemic treatment unless the lesion shows a well-delineated area of viable (contrast enhancement in the arterial phase) tumor that is >2 cm in the axial plane. (If the lesion is poorly demarcated or exhibits atypical enhancement as a result of the previous intervention, then it cannot be selected as a target lesion)
• Radiologic eligibility (measurable disease) must be must be confirmed by the BICR prior to randomization.
• Adequate bone marrow, renal and liver function as defined in the protocol.
• Performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Scale
• Age 18 years or older
• Have the ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information), and comply with the study and follow-up procedures.

Exclusion Criteria

• Any co-morbid condition that in the judgment of the investigator renders the subject at high risk of treatment complications or reduces the possibility of assessing clinical effect.
• Received prior investigational or non-investigational cytotoxic chemotherapy, hormonal therapy, biological therapy (including but not limited to monoclonal antibodies, small molecules or other immunotherapy) to treat hepatocellular carcinoma.
• History of organ allograft.
• Previously received mapatumumab or sorafenib.
• Underwent resection, radiofrequency ablation, radiation or chemoembolization within 4 weeks before enrollment or not recovered from such treatments.
• Need for concomitant anticancer therapy (surgery, radiation therapy, chemotherapy, immunotherapy, radiofrequency ablation) or other investigational agents during the study treatment period.
• Major surgery (i.e., the opening of a major body cavity, requiring the use of general anesthesia) within 4 weeks before enrollment; minor surgery (except for insertion of vascular access device) within 2 weeks before enrollment; or not yet recovered from the effects of the surgery.
• Systemic steroids within 1 week before enrollment except steroids used as part of an antiemetic regimen or maintenance-dose steroids for non-cancerous disease.
• Hepatic encephalopathy, per the investigator's evaluation.
• History of clinically significant gastrointestinal bleeding requiring procedural intervention (e.g., variceal banding, transjugular intrahepatic portosystemic shunt procedure, arterial embolization, topical coagulation therapy) within 4 weeks before enrollment.
• Gastrointestinal disease resulting in an inability to take oral medication or a requirement for intravenous hyperalimentation.
• History of any infection requiring hospitalization or intravenous antibiotics within 2 weeks before enrollment.
• Known brain or spinal cord metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids.
• Known human immunodeficiency virus infection.
• Unstable angina, myocardial infarction, cerebrovascular accident, >= Class II congestive heart failure according to the New York Heart Association Classification for Congestive Heart Failure within 6 months before enrollment.
• Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
• Uncontrolled hypertension (systolic blood pressure >150 millimeters of mercury [mmHg] or diastolic pressure >90 mmHg despite optimal medical management).
• Using and unable to discontinue use of concomitant strong CYP3A4 inducers (e.g., including but not limited to St. John's Wort, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital)
• Pregnant female or nursing mother. All females with an intact uterus (unless amenorrheic for the 24 months before enrollment) must have a negative serum pregnancy test at screening. All non-sterile or non-postmenopausal females must practice a medically accepted method of contraception over the course of the study and for 60 days after the last dose of study agent.
• Males who do not agree to use effective contraception during the study and for a period of 60 days following the final dose of study agent.
• Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s) or subject is receiving other investigational agents.
• Acute or chronic severe renal insufficiency (glomoerular filtration rate <30 milliliters [mL]/minute/1.73 square meters) or acute renal insufficiency of any severity due to the hepato-renal syndrome.
• Hepatitis B virus deoxyribonucleic acid (DNA) levels >2,000 international units/mL.

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

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Human Genome Sciences Inc., a GSK Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

Locations

GSK Investigational Site

Aurora, Colorado, United States

GSK Investigational Site

Shreveport, Louisiana, United States

GSK Investigational Site

Rochester, Minnesota, United States

GSK Investigational Site

Tupelo, Mississippi, United States

GSK Investigational Site

Newark, New Jersey, United States

GSK Investigational Site

Hershey, Pennsylvania, United States

GSK Investigational Site

Hershey, Pennsylvania, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Gdansk, , Poland

GSK Investigational Site

Olsztyn, , Poland

GSK Investigational Site

Poznan, , Poland

GSK Investigational Site

Szczecin, , Poland

GSK Investigational Site

Warsaw, , Poland

GSK Investigational Site

Warsaw, , Poland

GSK Investigational Site

San Juan, , Puerto Rico

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Cluj-Napoca, , Romania

GSK Investigational Site

Craiova, , Romania

GSK Investigational Site

Iași, , Romania

GSK Investigational Site

Kazan', , Russia

GSK Investigational Site

Krasnoyarsk, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Pyatigorsk, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Tomsk, , Russia

GSK Investigational Site

Yaroslavl, , Russia

GSK Investigational Site

Yekaterinburg, , Russia

GSK Investigational Site

Dnipropetrovsk, , Ukraine

GSK Investigational Site

Donetsk, , Ukraine

GSK Investigational Site

Kharkiv, , Ukraine

GSK Investigational Site

Kyiv, , Ukraine

GSK Investigational Site

Kyiv, , Ukraine

GSK Investigational Site

Lviv, , Ukraine

GSK Investigational Site

Uzhhorod, , Ukraine

GSK Investigational Site

Zaporizhia, , Ukraine

Countries

United States; Germany; Poland; Puerto Rico; Romania; Russia; Ukraine

References

Ciuleanu T, Bazin I, Lungulescu D, Miron L, Bondarenko I, Deptala A, Rodriguez-Torres M, Giantonio B, Fox NL, Wissel P, Egger J, Ding M, Kalyani RN, Humphreys R, Gribbin M, Sun W. A randomized, double-blind, placebo-controlled phase II study to assess the efficacy and safety of mapatumumab with sorafenib in patients with advanced hepatocellular carcinoma. Ann Oncol. 2016 Apr;27(4):680-7. doi: 10.1093/annonc/mdw004. Epub 2016 Jan 22.

Reference Type: BACKGROUND

PMID: 26802147 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Study Documents

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Clinical Study Report

View Document

Document Type: Individual Participant Data Set

View Document

Document Type: Dataset Specification

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

HGS1012-C1103

Identifier Type: OTHER

Identifier Source: secondary_id

200149

Identifier Type: -

Identifier Source: org_study_id