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

NCT ID: NCT01988493

Last Updated: 2022-08-24

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

117 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-06

Study Completion Date

2020-12-03

Brief Summary

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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.

Detailed Description

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Conditions

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Carcinoma, Hepatocellular

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1b: Tepotinib 300 mg

Participants received Tepotinib 300 milligram (mg) orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.

Group Type EXPERIMENTAL

Tepotinib 300 mg

Intervention Type DRUG

Participants received Tepotinib 300 milligram (mg) orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.

Phase 1b: Tepotinib 500 mg

Participants received Tepotinib 500 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.

Group Type EXPERIMENTAL

Tepotinib 500 mg

Intervention Type DRUG

Participants received Tepotinib 500 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.

Phase 1b: Tepotinib 1000 mg

Participants received Tepotinib 1000 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.

Group Type EXPERIMENTAL

Tepotinib 1000 mg

Intervention Type DRUG

Participants received Tepotinib 1000 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal

Phase 2: Tepotinib

Participants randomized to receive Tepotinib recommended Phase 2 dose (RP2D) determined from Phase 1b over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.

Group Type EXPERIMENTAL

Tepotinib

Intervention Type DRUG

Participants randomized to receive Tepotinib recommended Phase 2 dose (RP2D) determined from Phase 1b over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.

Phase 2 Sorafenib

Participants randomized to receive Sorafenib 400 mg orally twice daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.

Group Type EXPERIMENTAL

Sorafenib

Intervention Type DRUG

Participants randomized to receive Sorafenib 400 mg orally twice daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.

Interventions

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Tepotinib 300 mg

Participants received Tepotinib 300 milligram (mg) orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.

Intervention Type DRUG

Tepotinib 500 mg

Participants received Tepotinib 500 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.

Intervention Type DRUG

Tepotinib 1000 mg

Participants received Tepotinib 1000 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal

Intervention Type DRUG

Tepotinib

Participants randomized to receive Tepotinib recommended Phase 2 dose (RP2D) determined from Phase 1b over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.

Intervention Type DRUG

Sorafenib

Participants randomized to receive Sorafenib 400 mg orally twice daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Histologically or cytologically confirmed HCC
* Participants were either intermediate HCC of BCLC Stage B, who were not eligible for surgical and/or local-regional therapies or who had progressive disease (PD) after surgical and/or local-regional therapies (note: the local-regional therapy must not contain sorafenib), or advanced HCC of BCLC Stage C
* Participants who had disease progression on or were intolerant to the prior standard treatment for advanced HCC (phase Ib Korean subjects only)
* A tumor biopsy was required for determining MET status
* MET+ status (Phase 2 only), as determined by the central laboratory (Phase 1b retrospectively, Phase 2 for participant selection) were 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, was assessed by investigators according to the Package Insert and clinical judgment (Phase 2 only)
* Signed and dated informed consent indicating that the participants had 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 was judged by the investigator of at least 3 months

Exclusion Criteria

* Prior systemic anticancer treatment for advanced HCC, included 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 were 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 was defined in the protocol
* Hypertension uncontrolled by standard therapies
* Participants 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
* Particpants who had acute pancreatitis and/or chronic pancreatitis, with elevated lipase and/or amylase, clinical symptoms, and/or imaging studies that are indicative of the diagnosis (Mainland Chinese participants only)
* Known or suspected drug hypersensitivity to any ingredients of sorafenib (Phase 2 only) and MSC2156119J
* Female participants who were 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)
* Participants with any concurrent medical condition or disease that will potentially compromise the conduct of the study at the discretion of the investigators
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

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307 Hosptial of PLA

Beijing, Beijing Municipality, China

Site Status

Peking University Cancer Hospital

Beijing, Beijing Municipality, China

Site Status

Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA

Fuzhou, Fujian, China

Site Status

Sun Yat-sen University, Cancer Center

Guangzhou, Guangdong, China

Site Status

Nanfang Hospital

Guangzhou, Guangdong, China

Site Status

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Site Status

The Third Xiangya Hospital of Central South University

Changsha, Hu'nan, China

Site Status

Nanjing Bayi Hospital

Nanjing, Jiangsu, China

Site Status

Nanjing First Hospital Affiliated to Nanjing Medical University

Nanjing, Jiangsu, China

Site Status

Jilin Cancer Hospital

Changchun, Jilin, China

Site Status

Shanghai Cancer Hospital, Fudan University

Shanghai, Shanghai Municipality, China

Site Status

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality, China

Site Status

Cancer Hospital, Tianjin Medical University

Tianjin, Zhejiang, China

Site Status

Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine

Zhejiang, Zhejiang, China

Site Status

Beijing Friendship Hospital, Capital Medical University

Beijing, , China

Site Status

Dong-A University Hospital

Busan, , South Korea

Site Status

Pusan National University Hospital

Busan, , South Korea

Site Status

Keimyung University Dongsan Hospital

Daegu, , South Korea

Site Status

Kyungpook National University Hospital

Daegu, , South Korea

Site Status

National Cancer Center

Goyang-si, , South Korea

Site Status

CHA Bundang Medical Center, CHA University

Seongnam-si, , South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Site Status

Kyung Hee University Hospital

Seoul, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Gangnam Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, , South Korea

Site Status

Korea University Guro Hospital

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Ajou University Hospital

Suwon, , South Korea

Site Status

Pusan National University Yangsan Hospital

Yangsan, , South Korea

Site Status

Changhua Christian Hospital

Changhua, , Taiwan

Site Status

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status

Chi Mei Medical Center, Liou Ying

Tainan City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Mackay Memorial Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Chang Gung Memorial Hospital, Linkou

Taoyuan District, , Taiwan

Site Status

Countries

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China South Korea Taiwan

References

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Ryoo BY, Cheng AL, Ren Z, Kim TY, Pan H, Rau KM, Choi HJ, Park JW, Kim JH, Yen CJ, Lim HY, Zhou D, Straub J, Scheele J, Berghoff K, Qin S. Randomised Phase 1b/2 trial of tepotinib vs sorafenib in Asian patients with advanced hepatocellular carcinoma with MET overexpression. Br J Cancer. 2021 Jul;125(2):200-208. doi: 10.1038/s41416-021-01380-3. Epub 2021 May 10.

Reference Type RESULT
PMID: 33972742 (View on PubMed)

Xiong W, Hietala SF, Nyberg J, Papasouliotis O, Johne A, Berghoff K, Goteti K, Dong J, Girard P, Venkatakrishnan K, Strotmann R. Exposure-response analyses for the MET inhibitor tepotinib including patients in the pivotal VISION trial: support for dosage recommendations. Cancer Chemother Pharmacol. 2022 Jul;90(1):53-69. doi: 10.1007/s00280-022-04441-3. Epub 2022 Jun 30.

Reference Type DERIVED
PMID: 35771259 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://clinical-information.canada.ca/ci-rc/item/242300

Redacted Clinical study report, redacted clinical study protocol and redacted statistical analysis plan for this study is also available at the HC-PRCI portal (Health Canada-Public release of clinical information)

Other Identifiers

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200095-004

Identifier Type: -

Identifier Source: org_study_id

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