Efficacy, Safety, and Pharmacokinetic of MSC2156119J in Asian Subjects With Hepatocellular Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Merck KGaA
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01988493
First received: November 1, 2013
Last updated: August 12, 2014
Last verified: August 2014
  Purpose

This is an open-label, integrated, Phase 1b/2 trial to determine the recommended Phase 2 dose (RP2D) and to evaluate the efficacy, safety, and pharmacokinetic of MSC2156119J as first-line treatment versus sorafenib in subjects with MET+, Barcelona Clinic Liver Cancer (BCLC) Stage C, systemic treatment naive advanced hepatocellular carcinoma (HCC) and Child-Pugh class A liver function.


Condition Intervention Phase
Carcinoma, Hepatocellular
Drug: MSC2156119J
Drug: Sorafenib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Phase Ib/II Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of MSC2156119J as Monotherapy Versus Sorafenib in Asian Subjects With MET+ Advanced Hepatocellular Carcinoma and Child-Pugh Class A Liver Function

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Number of Subjects Experiencing Dose Limiting Toxicity (DLT) [ Time Frame: Up to Day 21 of Cycle 1 ] [ Designated as safety issue: Yes ]
  • Number of Subjects With Adverse Events (AEs) [ Time Frame: Baseline up to Day 30 after the last dose of study treatment ] [ Designated as safety issue: Yes ]
  • Time to Progression (TTP) Assessed by an Independent Review Committee (IRC) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    TTP assessed by an IRC will be measured from randomization until disease progression or study drug discontinuation assessed every 2 cycles up to Cycle 13, and thereafter every 4 cycles up to 2 years.


Secondary Outcome Measures:
  • Progression Free Survival (PFS) Time [ Time Frame: Time from randomization to disease progression or occurrence of death due to any cause within 42 days of either randomization or the last tumor assessment up to 12 months after last subject's first dose ] [ Designated as safety issue: No ]
  • Overall Survival (OS) Time [ Time Frame: Time from randomization to the date of death or up to 2 years whichever occur first ] [ Designated as safety issue: No ]
    Overall survival time will be measured from randomization to the date of death or up to 2 years whichever occur first.

  • TTP Assessed by Investigator [ Time Frame: Time from randomization until disease progression or study drug discontinuation assessed every 2 cycles up to Cycle 13, and thereafter every 4 cycles up to 12 months after last subject's first dose ] [ Designated as safety issue: No ]
  • Time-to-Symptomatic Progression (TTSP) [ Time Frame: Time from randomization up to Day 30 after the last dose of study treatment ] [ Designated as safety issue: No ]
  • Pharmacokinetics parameters: AUC (0-t), AUC (0-tau), AUC (0-infinity), Cmax, Cav, Cmin, tmax, CL/f, Vz/f, Vss/f, lambda_z and t1/2 [ Time Frame: Days 1 and 15 of Cycle 1 and Day 1 of Cycle 2 ] [ Designated as safety issue: No ]
  • Percentage of subjects with Objective Response (OR) [ Time Frame: Time from randomization until disease progression or study drug discontinuation assessed every 2 cycles up to Cycle 13, and thereafter every 4 cycles up to 12 months after last subject's first dose ] [ Designated as safety issue: No ]
  • Percentage of subjects with disease control according to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) criteria [ Time Frame: Time from randomization until disease progression or study drug discontinuation assessed every 2 cycles up to Cycle 13, and thereafter every 4 cycles up to 12 months after last subject's first dose ] [ Designated as safety issue: No ]
    Disease control is defined as proportion of subjects with complete response (CR), partial response (PR), or stable disease (SD) as the best overall response according to RECIST v1.1.


Estimated Enrollment: 158
Study Start Date: January 2014
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MSC2156119J Drug: MSC2156119J
MSC2156119J will be administered at a total dose range of 300-500 milligram (mg) orally once daily over a 21-day cycle until disease progression, intolerable toxicity or subject withdrawal. Dose adjustment will be done as per investigator's discretion based upon individual subject's tolerability.
Active Comparator: Sorafenib Drug: Sorafenib
Sorafenib will be administered at a dose of 400 mg orally twice daily over a 21-day cycle until disease progression, intolerable toxicity or subject withdrawal. Dose adjustment will be as per investigator's discretion based upon clinical circumstance, taking references to the description in the package insert.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed HCC
  • Subjects with advanced HCC of BCLC Stage C
  • A tumor biopsy is required for determining MET status
  • MET+ status (Phase 2 only), as determined by the central laboratory (phase 1b retrospectively, Phase 2 for subject selection) as defined in the protocol
  • Child-Pugh class A with no encephalopathy according to the screening assessment
  • Asian male or female, 18 years of age or older
  • Measurable disease in accordance with RECIST v1.1 (Phase 2 only)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2
  • Eligible for treatment with sorafenib, as assessed by investigators according to the Package Insert and clinical judgment (Phase 2 only)
  • Signed and dated informed consent indicating that the subject has been informed of all the pertinent aspects of the trial prior to enrollment
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures
  • Life expectancy judged by the investigator of at least 3 months

Exclusion Criteria:

  • Prior systemic anticancer treatment for advanced HCC, including targeted therapy (for example, sorafenib), chemotherapy, or any other investigational agent (Phase 2 only)
  • Prior treatment with any agent targeting the hepatocyte growth factor (HGF)/c-Met pathway
  • Prior local-regional therapy within 4 weeks prior to Day 1 of trial treatment
  • Prior history of liver transplant
  • Laboratory index at baseline as defined in the protocol
  • Past or current history of neoplasm other than HCC, except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least 5 years
  • Known central nervous system (CNS) or brain metastasis that is either symptomatic or untreated
  • Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested products
  • Clinically significant gastrointestinal bleeding within 4 weeks before trial entry
  • Peripheral neuropathy Grade greater than or equal to 2 (Common Terminology Criteria for Adverse Events [CTCAE] v4.0)
  • Impaired cardiac function as defined in the protocol
  • Hypertension uncontrolled by standard therapies
  • Subject with a family history of long QT syndrome or who take any agent that is known to prolong QT/QTc interval
  • Known human immunodeficiency virus (HIV) infection
  • Known or suspected drug hypersensitivity to any ingredients of sorafenib (Phase 2 only) and MSC2156119J
  • Female subjects who are pregnant or lactating, or males and females of reproductive potential not willing or not able to employ a highly effective method of birth control/contraception to prevent pregnancy from 2 weeks before receiving study drug until 3 months after receiving the last dose of study drug
  • Concurrent treatment with a non-permitted drug
  • Substance abuse, other acute or chronic medical or psychiatric condition, or laboratory abnormalities that may increase the risk associated with trial participation in the opinion of the investigator
  • Participation in another clinical trial within the past 28 days
  • Previous anticancer treatment-related toxicities not recovered to baseline or Grade 0-1 (except alopecia and peripheral neuropathy)
  • Subjects with any concurrent medical condition or disease that will potentially compromise the conduction of the study at the discretion of the investigators
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01988493

Contacts
Contact: Merck KGaA Communication Center +49 6151 72 5200 service@merckgroup.com

Locations
Germany
Please contact the Merck KGaA Communication Center Recruiting
Darmstadt, Germany
Contact    +49 6151 72 5200    service@merckgroup.com   
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Medical Responsible Merck KGaA
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01988493     History of Changes
Other Study ID Numbers: 200095-004
Study First Received: November 1, 2013
Last Updated: August 12, 2014
Health Authority: China: Food and Drug Administration
Korea: Ministry of Food and Drug Safety
Taiwan : Food and Drug Administration

Keywords provided by Merck KGaA:
Carcinoma, Hepatocellular
MSC2156119J
Sorafenib
Recommended Phase 2 dose

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014