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

NCT01258608 | Completed Phase 1 Results DMC

• 2 other identifiers: 200149HGS1012-C1103
• Study Type: interventional
• Target: 101
• Locations: 7 countries
• Sites: 43

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

Outcome Measures

Primary Outcomes (1)

• Time to Progression-Blinded Independent Central Review (BICR) Assessment

  Time to progression is defined as the time from randomization to radiologic disease progression based on blinded independent review (BICR) of imaging scans using modified Response Evaluation Criteria in Solid Tumors assessment (mRECIST) for hepatocellular carcinoma. The primary analysis was performed using Kaplan Meier methods. The median time to progression is reported with one-sided 90% confidence interval. Analysis was performed on the modified Intent to Treat (mITT) Population which comprised of all randomized participants who received at least part of 1 dose of study agent (mapatumumab/placebo and/or sorafenib) with participants analyzed according to the groups to which they were randomized. NA indicates upper limit was not measurable as one-sided confidence interval is presented.

  Randomization to maximum of 24.1 months

Secondary Outcomes (21)

• Time to Progression-Investigator Assessment

  Randomization to maximum of 52.9 months

• Median Overall Survival

  Randomization to maximum of 52.9 months

• Progression Free Survival-BICR Assessment

  Randomization to maximum of 24.1 months

• Progression Free Survival-Investigator Assessment

  Randomization to maximum of 52.9 months

• Percentage of Participants With Objective Response-BICR Assessment

  Randomization to maximum of 24.1 months

Study Arms (2)

Sorafenib plus mapatumumab

EXPERIMENTAL

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

Drug: Mapatumumab; Drug: Sorafenib

Sorafenib plus Placebo

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: Sorafenib

Interventions

Mapatumumab 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 plus mapatumumab

Placebo DRUG

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

Sorafenib plus Placebo

Sorafenib 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; Sorafenib plus mapatumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Human Genome Sciences Inc., a GSK Company: lead
• GlaxoSmithKline: collaborator

Study Sites (43)

GSK Investigational Site

Aurora, Colorado, 80045, United States

Location

GSK Investigational Site

Shreveport, Louisiana, 71103, United States

Location

GSK Investigational Site

Rochester, Minnesota, 55905, United States

Location

GSK Investigational Site

Tupelo, Mississippi, 38801, United States

Location

GSK Investigational Site

Newark, New Jersey, 07103, United States

Location

GSK Investigational Site

Hershey, Pennsylvania, 17033-0850, United States

Location

GSK Investigational Site

Hershey, Pennsylvania, 17033-, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15232, United States

Location

GSK Investigational Site

Munich, Bavaria, 81377, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60590, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Hamburg, 20246, Germany

Location

GSK Investigational Site

Gdansk, 80-952, Poland

Location

GSK Investigational Site

Olsztyn, 10-228, Poland

Location

GSK Investigational Site

Poznan, 61-878, Poland

Location

GSK Investigational Site

Szczecin, 71-730, Poland

Location

GSK Investigational Site

Warsaw, 02-507, Poland

Location

GSK Investigational Site

Warsaw, 04-125, Poland

Location

GSK Investigational Site

San Juan, 00927, Puerto Rico

Location

GSK Investigational Site

Bucharest, 022328, Romania

Location

GSK Investigational Site

Cluj-Napoca, 400015, Romania

Location

GSK Investigational Site

Craiova, 200385, Romania

Location

GSK Investigational Site

Iași, 700483, Romania

Location

GSK Investigational Site

Kazan', 420029, Russia

Location

GSK Investigational Site

Krasnoyarsk, 660133, Russia

Location

GSK Investigational Site

Moscow, 115478, Russia

Location

GSK Investigational Site

Moscow, 125284, Russia

Location

GSK Investigational Site

Moscow, 195067, Russia

Location

GSK Investigational Site

Pyatigorsk, 357502, Russia

Location

GSK Investigational Site

Saint Petersburg, 194017, Russia

Location

GSK Investigational Site

Saint Petersburg, 198255, Russia

Location

GSK Investigational Site

Tomsk, 634050, Russia

Location

GSK Investigational Site

Yaroslavl, 150054, Russia

Location

GSK Investigational Site

Yekaterinburg, 620036, Russia

Location

GSK Investigational Site

Dnipropetrovsk, 49044, Ukraine

Location

GSK Investigational Site

Donetsk, 83092, Ukraine

Location

GSK Investigational Site

Kharkiv, 61070, Ukraine

Location

GSK Investigational Site

Kyiv, 03022, Ukraine

Location

GSK Investigational Site

Kyiv, 03039, Ukraine

Location

GSK Investigational Site

Lviv, 79031, Ukraine

Location

GSK Investigational Site

Uzhhorod, 88014, Ukraine

Location

GSK Investigational Site

Zaporizhia, 69032, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 26802147 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

mapatumumab; Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

• GSK Clinical Trials

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2010
• First Posted: December 13, 2010
• Study Start: February 8, 2011
• Primary Completion: May 31, 2013
• Study Completion: November 29, 2017
• Last Updated: December 19, 2018
• Results First Posted: December 19, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will share

Locations

PL (6); US (9); DE (4); RO (4); RU (11); UA (8); PR (1)