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Carcinoma, HepatocellularPhase 1/2NCT01988493

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

A Phase 1/2 study testing Tepotinib 300 mg, Tepotinib 500 mg and Tepotinib 1000 mg in people with Carcinoma, Hepatocellular, run by Merck KGaA, Darmstadt, Germany at 43 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Hepatocellular
What is being tested?
Tepotinib 300 mg, Tepotinib 500 mg and Tepotinib 1000 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
117 participants
Where
43 sitesin 3 countries
Study dates
6 Jan 2014to 3 Dec 2020
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 13Show fewer
  • 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

Who cannot join

  • 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
Show all 22Show fewer
  • 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

Trial locations and contacts

43 sites in 3 countries.

43 sites in 3 countries

South Korea18 sites

  • Dong-A University Hospital

    Busan, 602-715

  • Pusan National University Hospital

    Busan, 602-739

  • Keimyung University Dongsan Hospital

    Daegu, 41931

  • Kyungpook National University Hospital

    Daegu, 700-721

  • National Cancer Center

    Goyang-si, 10408

  • CHA Bundang Medical Center, CHA University

    Seongnam-si, 13496

  • Seoul National University Bundang Hospital

    Seongnam-si, 13620

  • Kyung Hee University Hospital

    Seoul, 02447

  • Korea University Anam Hospital

    Seoul, 02841

  • Severance Hospital, Yonsei University

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

  • Gangnam Severance Hospital, Yonsei University Health System

    Seoul, 06273

  • Samsung Medical Center

    Seoul, 06351

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

    Seoul, 06591

  • Korea University Guro Hospital

    Seoul, 08308

  • Seoul National University Hospital

    Seoul, 110744

  • Ajou University Hospital

    Suwon, 443-380

  • Pusan National University Yangsan Hospital

    Yangsan, 626-770

Other trials in South Korea

China15 sites

  • 307 Hosptial of PLA

    Beijing, Beijing Municipality, 100071

  • Peking University Cancer Hospital

    Beijing, Beijing Municipality, 100142

  • Beijing Friendship Hospital, Capital Medical University

    Beijing, 100050

  • Jilin Cancer Hospital

    Changchun, Jilin, 130012

  • The Third Xiangya Hospital of Central South University

    Changsha, Hu'nan, 410013

  • Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA

    Fuzhou, Fujian, 350025

  • Sun Yat-sen University, Cancer Center

    Guangzhou, Guangdong, 510060

  • Nanfang Hospital

    Guangzhou, Guangdong, 510515

  • Harbin Medical University Cancer Hospital

    Harbin, Heilongjiang, 150081

  • Nanjing Bayi Hospital

    Nanjing, Jiangsu, 210002

  • Nanjing First Hospital Affiliated to Nanjing Medical University

    Nanjing, Jiangsu, 210029

  • Shanghai Cancer Hospital, Fudan University

    Shanghai, Shanghai Municipality, 200032

  • Zhongshan Hospital Fudan University

    Shanghai, Shanghai Municipality, 200032

  • Cancer Hospital, Tianjin Medical University

    Tianjin, Zhejiang, 300060

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

    Zhejiang, Zhejiang, 310016

Other trials in China

Taiwan10 sites

  • Changhua Christian Hospital

    Changhua, 50004

  • Kaohsiung Medical University Chung-Ho Memorial Hospital

    Kaohsiung City, 807

  • Kaohsiung Chang Gung Memorial Hospital

    Kaohsiung City, 83301

  • Taichung Veterans General Hospital

    Taichung, 40705

  • National Cheng Kung University Hospital

    Tainan, 704

  • Chi Mei Medical Center, Liou Ying

    Tainan, 736

  • National Taiwan University Hospital

    Taipei, 100

  • Mackay Memorial Hospital

    Taipei, 10449

  • Taipei Veterans General Hospital

    Taipei, 11217

  • Chang Gung Memorial Hospital, Linkou

    Taoyuan, 333

Other trials in Taiwan

About this study

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

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.

Being tested
Tepotinib 300 mg, Tepotinib 500 mg, Tepotinib 1000 mg, Tepotinib, Sorafenib
Keywords
Carcinoma, Hepatocellular, MSC2156119J, Sorafenib, Recommended Phase 2 dose
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tepotinib 300 mgDrug

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

  • Tepotinib 500 mgDrug

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

  • Tepotinib 1000 mgDrug

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

  • TepotinibDrug

    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.

  • SorafenibDrug

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

Study groups in NCT01988493
Study groupRoleWhat they receive
Phase 1b: Tepotinib 300 mgExperimentalParticipants received Tepotinib 300 milligram (mg) orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.
Receives: Drug: Tepotinib 300 mg
Phase 1b: Tepotinib 500 mgExperimentalParticipants received Tepotinib 500 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.
Receives: Drug: Tepotinib 500 mg
Phase 1b: Tepotinib 1000 mgExperimentalParticipants received Tepotinib 1000 mg orally once daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.
Receives: Drug: Tepotinib 1000 mg
Phase 2: TepotinibExperimentalParticipants 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.
Receives: Drug: Tepotinib
Phase 2 SorafenibExperimentalParticipants randomized to receive Sorafenib 400 mg orally twice daily over a 21-day cycle until disease progression, intolerable toxicity or participant withdrawal.
Receives: Drug: Sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1b: Number of Participants Experiencing Dose Limiting Toxicity

    Dose limiting toxicity (DLT) was defined as toxicities at any dose level and judged to be related to the study treatment by investigator and/or the sponsor. DLTs included Grade 4 neutropenia for more than 7 days; Grade greater than or equal to (>=) 3 febrile neutropenia for more than 1 day; Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with non-traumatic bleeding; Grade >= 3 uncontrolled nausea/vomiting and/or diarrhea despite adequate and optimal treatment and Grade >= 3 any non-hematological adverse event (AE), except the aforementioned gastrointestinal events and alopecia. Number of participants who experienced DLT during phase 1b were reported.

    Measured: Day 1 to Day 21 of Cycle 1 (each cycle is 21 days)

  2. Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

    An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and assessed up to 94 weeks. TEAEs include both Serious TEAEs and non-serious TEAEs.

    Measured: Baseline up to Day 30 after the last dose of study treatment, assessed up to 94 weeks

  3. Phase 2: Time to Progression (TTP) Based on Tumor Assessment by an Independent Review Committee (IRC)

    TTP was defined as the time in months from randomization to date of the observation of radiological progressive disease (PD) (based on Response Evaluation Criteria in Solid Tumors [RECIST] v1.1) assessed by an IRC. PD is defined as at least 20 percent (%) increase in sum of diameters of target lesions, taking as reference as smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must demonstrate an absolute increase of at least 5 millimeter (mm).

    Measured: From randomization to date of the observation of radiological progressive disease, assessed up to maximum 3.8 years

Secondary outcomes (21)

  1. Phase 2: Progression Free Survival (PFS) Time Based on Tumor Assessment by the Independent Review Committee (IRC)

    Progression-free survival (PFS) time was defined as the time in months from randomization to either first observation of disease progression (based on RECIST v1.1) or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 millimeter(mm). PFS was measured using Kaplan-Meier (KM) estimates.

    Measured: Up to 2.8 years

  2. Phase 2: Overall Survival (OS)

    Overall survival time was measured as time in months between the date of randomization and the date of death.

    Measured: Time from randomization to the date of death or up to 6.9 years

  3. Phase 2: Time to Progression (TTP) Based on Tumor Assessment by Investigator

    TTP was defined as the time in months from randomization to date of the observation of radiological PD (based on RECIST v1.1) assessed by the investigator. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm.

    Measured: From randomization to date of the observation of radiological progressive disease, assessed up to maximum 2.8 years

  4. Phase 1b: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-infinity) of Tepotinib

    The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.

    Measured: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days)

  5. Phase 1b: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Tepotinib

    Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration is at or above the lower limit of quantification (LLLQ). AUC(0-t) was calculated according to the mixed log-linear trapezoidal rule.

    Measured: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days)

  6. Phase 1b: Area Under the Plasma Concentration-Time Curve Within 1 Dosing Interval (AUC 0-tau) of Tepotinib

    AUC (0-tau) is the area under the plasma concentration time curve within 1 dosing interval.

    Measured: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days)

  7. Phase 1b: Maximum Observed Plasma Concentration (Cmax) of Tepotinib

    Cmax is the maximum observed plasma concentration obtained directly from the concentration versus time curve.

    Measured: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days)

  8. Phase 1b: Minimum Observed Plasma Concentration (Cmin) of Tepotinib

    Cmin is minimum observed plasma concentration obtained directly from the concentration versus time curve.

    Measured: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 15 of Cycle 1 (each Cycle is 21 days)

  9. Phase 1b: Average Observed Plasma Concentration (Cav) of Tepotinib

    Cavg is the average plasma concentration within 1 dosing interval obtained directly from the concentration versus time curve.

    Measured: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 15 of Cycle 1 (each Cycle is 21 days)

  10. Phase 1b: Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib

    Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve.

    Measured: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days)

  11. Phase 1b: Apparent Volume of Distribution During the Terminal Phase (Vz/f) of Tepotinib

    The Vz/f was defined as the theoretical volume in which the total amount of required to uniformly distribute to produce the desired plasma concentration. Apparent volume of distribution after oral dose (Vz/F) was influenced by the fraction absorbed. The Vz/f was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant Lambda(z). Vz/f=Dose/AUC(0-inf)* Lambda(z).

    Measured: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days)

  12. Phase 1b: Apparent Total Body Clearance From Plasma (CL/f) of Tepotinib

    The CL/f is a measure of the rate at which it was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed. The CL/F from plasma was calculated using the formula: Dose divided by area under the concentration time curve from time zero to infinity (AUC0-inf).

    Measured: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days)

  13. Phase 1b: Apparent Volume of Distribution During the Steady State (Vss/f) of Tepotinib

    Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss/f after oral dose was influenced by the fraction absorbed.

    Measured: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days)

  14. Phase 1b: Apparent Terminal Elimination Rate Constant Lambda(z) of Tepotinib

    Lambda(z) was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.

    Measured: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days)

  15. Phase 1b: Apparent Terminal Half-life (t1/2) of Tepotinib

    Apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination.

    Measured: Predose and at 0.25, 0.5, 1, 2, 4, 8, 10, and 24 hours postdose; Day 1 and Day 15 of Cycle 1 (each Cycle is 21 days)

  16. Phase 2: Time-to-Symptomatic Progression (TTSP)

    Time-to-symptomatic progression was defined as time (in months) from first study drug administration to the date of deterioration of symptoms assessed by Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index 8 (FHSI-8) (defined as at least a 4-point increase, i.e., higher score, compared with baseline value), or deterioration to Eastern Cooperative Oncology Group (ECOG) performance score 4, or death. FHSI-8 assesses hepatobiliary cancer symptoms with total score ranges from 0 to 32 (0 = the best quality of life; 32 = the worst quality of life with severe symptoms). ECOG assess participant's performance status on a scale of 0 to 5, where 0=fully active and 5=dead.

    Measured: Up to 6.9 years

  17. Phase 2: Objective Response Rate (ORR) Based on Tumor Assessment by the IRC

    The objective response rate (ORR) was defined as the percentage of participants who had achieved complete response (CR) or partial response (PR) as the best overall response according to radiological assessments as adjudicated by the IRC from randomization until the first occurrence of PD. CR: Complete Response (CR) defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started.

    Measured: Time from randomization until the first occurrence of PD assessed up to 6.9 years

  18. Phase 2: Percentage of Participants With Disease Control Based on Tumor Assessment by IRC According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria

    Disease control was defined as CR, PR, or stable disease (SD) as the best overall response according to radiological assessments as adjudicated by the IRC from randomization until the first occurrence of PD. CR defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD was defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started. Percentage of participants with disease control were reported.

    Measured: Time from randomization until the first occurrence of PD assessed up to 6.9 years

  19. Phase 2: Progression-free Survival (PFS) Based on Tumor Assessment by the Investigator

    Progression-free survival (assessed by the Investigator) time was defined as the time in months from randomization to either first observation of radiologically confirmed progression disease by the investigator or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. PFS was measured using Kaplan-Meier (KM) estimates.

    Measured: Time from randomization to disease progression or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment, assessed up to 6.9 years

  20. Phase 2: Objective Response Rate (ORR) Based on Tumor Assessment by the Investigator

    The objective response rate was defined as the percentage of participants who had achieved CR or PR as the best overall response according to radiological assessments as adjudicated by the investigator from randomization until the first occurrence of PD. CR defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD was defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started.

    Measured: Time from randomization until the first occurrence of PD assessed up to 6.9 years

  21. Phase 2: Percentage of Participants With Disease Control Based on Tumor Assessment by Investigator According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria

    Disease control was defined as CR, PR, or stable disease (SD) as the best overall response according to radiological assessments as adjudicated by the IRC from randomization until the first occurrence of PD. CR defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD was defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started. Percentage of participants with disease control were reported.

    Measured: Approximately up to 6.9 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Nov 2013 (estimated)
  2. Study start6 Jan 2014
  3. Primary completion5 Feb 2018
  4. Study completion3 Dec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
117 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01988493
Sponsor's protocol ID
200095-004
Status last verified
Aug 2022
First submitted
1 Nov 2013
Last updated
24 Aug 2022
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 33972742

  • 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.

    PubMed 35771259

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tepotinib 300 mg, Tepotinib 500 mg and Tepotinib 1000 mg in people with Carcinoma, Hepatocellular, run by Merck KGaA, Darmstadt, Germany at 43 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 43 sites in South Korea, China, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b: Number of Participants Experiencing Dose Limiting Toxicity (time frame: Day 1 to Day 21 of Cycle 1 (each cycle is 21 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01988493, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2022.

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