Clinical trial NCT01832506: A Japanese Phase 1 Trial of c-Met Inhibitor MSC2156119J in Subjects With Solid Tumors
Official title: A Japanese Multicenter, Open Label, Phase I Trial of c-Met Inhibitor MSC2156119J Given Orally as Monotherapy to Subjects With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Solid Tumors
MSC2156119J
c-Met inhibitor
Japanese
Phase 1
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2013-04-16
Enrollment: 12
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Japanese multicenter, open-label, Phase 1 study to evaluate safety and efficacy of MSC2156119J in subjects with malignant solid tumor which is refractory to standard therapy or to which no effective standard therapy is applicable.


Eligibility criteria: Inclusion Criteria:

* A subject with a histologically or cytologically confirmed diagnosis of malignant solid tumor which is refractory to standard therapy or to which no effective standard therapy is applicable
* An archived tumor tissue is available or biopsy of tumor tissues can be newly performed
* A Japanese male or female, age greater than or equal to (\>=) 20 years
* A subject who has read the Subject Information Sheet and understood the details of this clinical trial, and is willing and able to give his/her informed consent.
* A female of child-bearing potential must have a negative blood pregnancy test result at her screening period. A female subject of child-bearing potential must be willing to avoid pregnancy by using an adequate method of contraception Life expectancy is at least 3 months
* Other inclusion criteria apply

Exclusion Criteria:

* Known Human immunodeficiency virus (HIV) positivity, active hepatitis C, or active hepatitis B
* Presence of liver fibrosis or liver cirrhosis that has been histologically diagnosed
* Signs or symptoms that suggest transmissible spongiform encephalopathy
* Received major surgery within 6 weeks before Day 1 in Cycle 1
* Known drug abuse or alcohol abuse
* Known hypersensitivity to any of the trial treatment ingredients
* Hematological test abnormalities
* Renal impairment as defined in the protocol
* Liver dysfunction as defined in the protocol
* History or presence of central nervous system metastasis
* History or presence of disease or condition that may hamper compliance or absorption of the investigational medicinal product (IMP) due to difficulty in swallowing or absorption
* Poor performance status of Eastern Cooperative Oncology Group Performance status (ECOG PS) \>= 2
* Received any anti-cancer therapy days Received extensive prior radiotherapy that irradiates more than 30 percent of bone marrow
* Received any radiotherapy within 4 weeks before Day 1 in Cycle 1
* Pregnancy and lactation period
* History of receiving treatment with any c-Met signaling pathway inhibitor
* Participation in another interventional clinical trial within the past 30 days from Day 1 in Cycle 1
* Other significant disease that in the Investigator's opinion would exclude the subject from the trial
* Legal incapacity or limited legal capacity
* Other exclusion criteria apply

Primary outcomes:
measure: Number of Subjects Experiencing Dose Limiting Toxicity (DLT)
timeFrame: Cycle 1 (Day 1 up to 21)
Secondary outcomes:
measure: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs or TEAEs Leading To Death
timeFrame: Baseline Up to 30 days after last dose of study drug administration (55.1 weeks)
measure: Number of Subjects With Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score of 2 or Higher
timeFrame: Baseline up to 30 days after last dose of study drug administration (55.1 weeks)
measure: Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J
timeFrame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
measure: Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J
timeFrame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
measure: Time to Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J
timeFrame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
measure: Time to Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J
timeFrame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
measure: Apparent Terminal Half-life (t1/2) of MSC2156119J
timeFrame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 and Day 14 Cycle 1
measure: Area Under the Concentration Time Curve From Time Zero to Extrapolated Infinite Time (AUC[Inf]) of MSC2156119J
timeFrame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 and Day 14 Cycle 1
measure: Apparent Body Clearance (CL/f) of MSC2156119J
timeFrame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 and Day 14 Cycle 1
measure: Apparent Volume of Distribution Associated To The Terminal Phase (Vz/f) of MSC2156119J
timeFrame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 and Day 14 Cycle 1
measure: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time t (AUC0-t) After Single Dose of MSC2156119J
timeFrame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1
measure: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time t (AUC0-t) After Multiple Dose of MSC2156119J
timeFrame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1
measure: Number of Subjects With Best Overall Response (BOR)
timeFrame: Day 21 of Cycle 2 and each subsequent cycle up to a maximum of 51.1 weeks
measure: Number of Subjects With Clinical Benefit
timeFrame: Day 21 of Cycle 2 and each subsequent cycle up to a maximum of 51.1 weeks
measure: Progression-free Survival (PFS)
timeFrame: Day 21 of Cycle 2 and each subsequent cycle up to a maximum of 51.1 weeks
Other outcomes:
Locations:
city: Kashiwa
country: Japan
facility: Research site
city: Shizuoka
country: Japan
facility: Research site
Study officials:
affiliation: Merck Serono Co., Ltd., Japan
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Shitara K, Yamazaki K, Tsushima T, Naito T, Matsubara N, Watanabe M, Sarholz B, Johne A, Doi T. Phase I trial of the MET inhibitor tepotinib in Japanese patients with solid tumors. Jpn J Clin Oncol. 2020 Aug 4;50(8):859-866. doi: 10.1093/jjco/hyaa042.
citation: 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.