We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

First-in-Man, Dose-escalation Trial of C-met Kinase Inhibitor MSC2156119J in Subjects With Advanced Solid Tumors

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01014936
First Posted: November 17, 2009
Last Update Posted: August 23, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Merck KGaA
Information provided by (Responsible Party):
EMD Serono
  Purpose

This is a an open-label, dose-escalation, first-in-man (FIM) study designed to explore MSC2156119J, in subjects with advanced solid tumors who have not responded to previous therapies or for whom no other therapies are available.

Subjects will be assigned one of the dosing regimens:

  • Regimen 1: MSC2156119J once daily for 14 days, followed by 7 days with no treatment (21-day cycle)
  • Regimen 2: MSC2156119J three times per week (e.g., Days 1, 3, and 5) for three weeks (21-day cycle)
  • Regimen 3: MSC2156119J every day for three weeks (21-day cycle)

Condition Intervention Phase
Patients With Solid Tumors, Either Refractory to Standard Therapy or for Which no Effective Standard Therapy is Available Drug: MSC2156119J Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Open-label, Non-randomized, Dose-escalation First-in-man Trial to Investigate the c-Met Kinase Inhibitor MSC2156119J Under Three Different Regimens in Subjects With Advanced Solid Tumors

Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Number of Subjects With Any Dose Limiting Toxicity (DLT) [ Time Frame: Day 1, 3, 8, 14, 17 of Cycle 1 (for Regimen 1 and 3); Day 1, 3, 8, 15, 19 of Cycle 1 (for Regimen 2) ]
    DLT was defined as one of the following adverse events (AEs) observed during Cycle1, regardless of MSC2156119J relationship, excluding AEs assessed by investigator exclusively related to subject's underlying disease or medical condition: Grade 4 neutropenia for >7 days; Grade >=3 febrile neutropenia for >1 day; Grade 4 thrombocytopenia/Grade 3 with bleeding; Grade >=3 nausea and emesis, despite optimal treatment; Grade >=3 non-hematological AE, except emesis and nausea with no adequate therapy and alopecia, Grade >= 3 liver AE with a recovery period of >7 days or to Grade <=1 for subjects without liver metastases or to <=2 for subjects with liver metastases; Grade >=3 lipase and/or amylase rise with pancreatitis confirmation, either based on clinical or radiological signs. Any AE not otherwise defined as a DLT that, due to prolonged recovery to Grade <=1 or baseline status, leads to delay of above 21 days in planned administration of study drug.

  • Recommended Phase 2 Dose (RP2D) [ Time Frame: Cycle 1 (Day 1 to Day 21) ]
    MTD was defined as the dose level at which 2 out of 3 subjects or 2 out of 6 subjects experienced a DLT. The primary endpoint was to determine MTD of MSC2156119J for each of the 3 treatment regimens in subjects with advanced solid tumors. However, during the course of the trial it was established that the MTD could not be determined and instead, RP2D was to be determined.

  • Number of Subjects With Treatment-Related Adverse Events [ Time Frame: Baseline up to 158.01 weeks ]
    Related AE was defined as any untoward medical occurrence which was considered to have a relationship with the study drug (suspected to be reasonably related to the study drug or AE was medically (pharmacologically/clinically) attributed to the study drug as per Investigator's assessment.


Secondary Outcome Measures:
  • Number of Subjects With Treatment-Emergent AEs (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death [ Time Frame: Baseline up to 158.01 weeks ]
    AE was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. 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 up to 33 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. TEAEs include both Serious TEAEs and non-serious TEAEs.

  • Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 1 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
  • Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 2 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
  • Observed Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J: Regimen 3 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
  • Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 1 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1 ]
  • Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 2 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1 ]
  • Observed Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J: Regimen 3 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1 ]
    Reporting group "MSC2156119J 1200 mg: Fasted" is not applicable for Multiple Dosing because only one subject was erroneously dosed with 1200 mg in fasted state as a single dose in Regimen 3. For multiple dose PK profile (Study Day 14), this subject was included in reporting group "MSC2156119J 1400 mg: Fed".

  • Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 1 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
  • Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 2 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48, 49.32 hours post-dose on Day 1 Cycle 1 ]
  • Time To Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J: Regimen 3 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
  • Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 1 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1 ]
  • Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 2 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1 ]
  • Time To Reach Maximum Plasma Concentration (Tmax) After Multiple Dose of MSC2156119J: Regimen 3 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1 ]
    Reporting group "MSC2156119J 1200 mg: Fasted" is not applicable for Multiple Dosing because only one subject was erroneously dosed with 1200 mg in fasted state as a single dose in Regimen 3. For multiple dose PK profile (Study Day 14), this subject was included in reporting group "MSC2156119J 1400 mg: Fed".

  • Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 1 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    Apparent Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.

  • Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 2 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    Apparent Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.

  • Apparent Terminal Half-life ( t1/2) After Single Dose Of MSC2156119J: Regimen 3 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    Apparent Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.

  • Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 1 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1 ]
    Apparent terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.

  • Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 2 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1 ]
    Apparent terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.

  • Apparent Terminal Half-life (t1/2) After Multiple Dose Of MSC2156119J: Regimen 3 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1 ]
    Apparent terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.

  • Area Under Plasma Concentration Versus Time Curve From Time Zero to Last Sampling Time (AUC0-t) After First Dose of MSC2156119J: Regimen 1 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.

  • Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After First Dose of MSC2156119J: Regimen 2 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the LLQ. AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.

  • Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After First Dose of MSC2156119J: Regimen 3 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the LLQ. AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.

  • Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After Multiple Dose of MSC2156119J : Regimen 1 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1 ]
    Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the LLQ. AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.

  • Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After Multiple Dose of MSC2156119J : Regimen 2 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1 ]
    Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the LLQ. AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.

  • Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time (AUC0-t) After Multiple Dose of MSC2156119J : Regimen 3 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1 ]
    Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the LLQ. AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. Reporting group "MSC2156119J 1200 mg: Fasted" is not applicable for Multiple Dosing because only one subject was erroneously dosed with 1200 mg in fasted state as a single dose in Regimen 3. For multiple dose PK profile (Study Day 14), this subject was included in reporting group "MSC2156119J 1400 mg: Fed".

  • Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) After Single Dose Of MSC2156119J: Regimen 1 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the LLQ and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

  • Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) After Single Dose Of MSC2156119J: Regimen 2 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the LLQ and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

  • Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) After Single Dose Of MSC2156119J: Regimen 3 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the LLQ and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

  • Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 1 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
  • Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 2 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48 hours post-dose on Day 1 Cycle 1 ]
  • Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Single Dose of MSC2156119: Regimen 3 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
  • Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 1 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1 ]
  • Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 2 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24, 48 hours post-dose on Day 19 Cycle 1 ]
  • Area Under Plasma Concentration Versus Time Curve Within One Dosing Interval (AUCtau) After Multiple Dose of MSC2156119: Regimen 3 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1 ]
    Reporting group "MSC2156119J 1200 mg: Fasted" is not applicable for Multiple Dosing because only one subject was erroneously dosed with 1200 mg in fasted state as a single dose in Regimen 3. For multiple dose PK profile (Study Day 14), this subject was included in reporting group "MSC2156119J 1400 mg: Fed".

  • Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 1 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0−inf.

  • Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 2 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0−inf.

  • Apparent Body Clearance (CL/f) After First Dose of MSC2156119J: Regimen 3 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent body clearance of the drug from plasma, CL= Dose/AUC0−inf.

  • Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 1 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    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 serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz.

  • Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 2 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    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 serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz.

  • Apparent Volume of Distribution (Vz/f) After First Dose of MSC2156119J: Regimen 3 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    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 serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz.

  • Apparent Volume of Distribution (Vz/f) After Multiple Dose of MSC2156119J: Regimen 1 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1 ]
    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 serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz.

  • Apparent Volume of Distribution (Vz/f) After Multiple Dose of MSC2156119J: Regimen 2 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1 ]
    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 serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz.

  • Apparent Volume of Distribution (Vz/f) After Multiple Dose of MSC2156119J: Regimen 3 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1 ]
    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 serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by λz.

  • Apparent Terminal Rate Constant (λz) After Single Dose of MSC2156119J: Regimen 1 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

  • Apparent Terminal Rate Constant (λz) After Single Dose of MSC2156119J: Regimen 2 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

  • Apparent Terminal Rate Constant (λz) After Single Dose of MSC2156119J: Regimen 3 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1 ]
    Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

  • Apparent Terminal Rate Constant (λz) After Multiple Dose of MSC2156119J: Regimen 1 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1 ]
    Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

  • Apparent Terminal Rate Constant (λz) After Multiple Dose of MSC2156119J: Regimen 2 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 19 Cycle 1 ]
    Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

  • Apparent Terminal Rate Constant (λz) After Multiple Dose of MSC2156119J: Regimen 3 [ Time Frame: pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1 ]
    Apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

  • Absolute Change From Baseline in Cytoplasm and Membrane H-Score at Day 1 Cycle 2 [ Time Frame: Baseline, Day 1 Cycle 2 ]
    Histo score (H-score) is a composite score that comprises of intensity and percentage of staining and is used for assessing the amount of protein or phospho-protein present in a biopsy sample. The composite score obtained by H-score is derived by summing the percentages of cell staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+; where 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). The composite H-score ranges from 0 to 300, with a score of 0 representing the absence of any of the target protein and an H-score of 300 representing maximum staining and intensity of the target protein.

  • Fold Change From Baseline in Cytoplasm and Membrane H-Score at Day 1 Cycle 2 [ Time Frame: Baseline, Day 1 Cycle 2 ]
    Histo score (H-score) is a composite score that comprises of intensity and percentage of staining and is used for assessing the amount of protein or phospho-protein present in a biopsy sample. The composite score obtained by H-score is derived by summing the percentages of cell staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+; where 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). The composite H-score ranges from 0 to 300, with a score of 0 representing the absence of any of the target protein and an H-score of 300 representing maximum staining and intensity of the target protein. Fold change = on-treatment value/ baseline value

  • Number of Subjects With Monovalent Antagonist Antibody to Receptor MET (MetMAb) Score (MMS) [ Time Frame: Day 1 Cycle 2 ]
    MetMAb score was used to assess the tumor c-Met expression and ranged from 0 to 3, where a score of 0 corresponds to the lowest c-Met expression and a score of 3 corresponds to the highest c-Met expression in tumor tissue by immunohistochemistry.

  • Relative Percentage Change In Sum of Longest Diameter (SOLD) of Target Lesions to Post-Baseline Nadir [ Time Frame: Baseline, On Treatment (up to 153.3 weeks) ]
    The post-baseline nadir was defined as the the smallest SOLD recorded after baseline. The relative change (%) was derived based on the SOLD of target lesions as follows: 100* (SOLD at post-baseline nadir - baseline SOLD) / baseline SOLD.

  • Number of Subjects With Best Overall Response (BOR) [ Time Frame: Baseline up to 153.3 weeks ]
    Number of subjects with BOR in each category (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) was reported. CR: defined as disappearance of all target and all non-target lesions. 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 sum of longest diameter of target lesions, taking as reference the baseline sum of longest diameter. PD:defined as at least a 20% increase in sum of longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions. SD: defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of longest diameter while on study.

  • Progression-free Survival (PFS) [ Time Frame: Baseline up to 153.3 weeks ]
    PFS was defined as the time (in months) between the first dosing day and radiographic PD or clinical PD (as recorded on the study termination form) or death, if death occurred within 12 weeks (84 days) after the last tumor assessment without documented progressive disease, whichever occurred first. Any subject with neither assessment of tumor progression, nor death within 12 weeks after last tumor assessment date was censored on the date of last tumor assessment.


Enrollment: 149
Actual Study Start Date: November 30, 2009
Study Completion Date: October 31, 2015
Primary Completion Date: October 31, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MSC2156119J Regimen 1
Subjects will be administered with micronized or non-micronized MSC2156119J in dose ranging from 30 mg to 400 mg (capsule formulation) once daily for 14 days, followed by 7 days with no treatment (21-day cycle) in Regimen 1.
Drug: MSC2156119J
Other Names:
  • EMD 1214063
  • Tepotinib
Experimental: MSC2156119J Regimen 2
Subjects will be administered with micronized or non-micronized MSC2156119J in dose ranging from 60 mg to 315 mg (capsule formulation) once daily 3 times per week for 3 weeks (21-day cycle) in Regimen 2.
Drug: MSC2156119J
Other Names:
  • EMD 1214063
  • Tepotinib
Experimental: MSC2156119J Regimen 3
Subjects will be administered with micronized MSC2156119J in dose ranging from 300 mg to 1400 mg (capsule or tablet formulation) once daily for 21 days (21-day cycle) in Regimen 3.
Drug: MSC2156119J
Other Names:
  • EMD 1214063
  • Tepotinib

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject should read and fully understand the requirements of the trial, be willing to comply with all trial visits and assessments, and be willing and able to give informed consent
  2. Histologically or cytologically confirmed solid tumor, either refractory to standard therapy or for which no effective standard therapy is available
  3. Measurable or evaluable disease, as defined by RECIST 1.0
  4. Estimated life expectancy greater than (>) three months
  5. Men or women aged greater than or equal to (>=) 18 years
  6. Women of childbearing potential must have a negative blood pregnancy test at the Screening Visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are post-menopausal for at least 12 months, are surgically sterile, or are sexually inactive.
  7. Subjects and their partners must be willing to avoid pregnancy during the trial and until three months after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator, such as a two-barrier method or one-barrier method with spermicide or intrauterine device. This requirement begins two weeks before receiving the first trial treatment and ends one month after receiving the last treatment.
  8. ECOG performance status of 0 to 2
  9. Adequate hematological function:

    • Hemoglobin >= 9.0 g/dL
    • Neutrophils > 1.5 x 109/L
    • Platelets >= 75 x 109/L
  10. Adequate liver function:

    • Total bilirubin less than or equal to (<=) 1.5 x ULN (upper limit to normal)
    • AST/ ALT ≤ 2.5 x ULN

    For subjects with liver metastases:

    • Total bilirubin ≤ 1.5 x ULN
    • AST/ ALT ≤ 5 x ULN
  11. Adequate renal function:

    • Serum creatinine < 1.5 x ULN, and/or
    • Calculated creatinine clearance > 60 mL/min
  12. Resolution of all acute chemotherapy, radiotherapy or surgery-related AEs to Grade <= 2, except for alopecia
  13. Recovery from any surgical intervention
  14. Subjects enrolling after the MTD has been determined must present specific c Met alterations (mutation, overexpression, amplification

Exclusion Criteria:

  1. Received chemotherapy, immunotherapy, hormonal therapy (except subjects with prostate cancer), biologic therapy, or any other investigational agent or anticancer therapy within 28 days (or five half-lives for non-cytotoxics, whichever is shorter), of Day 1 of trial treatment (six weeks for nitrosureas or mitomycin C)
  2. Received extensive prior radiotherapy on more than 30% of bone marrow
  3. Symptomatic primary tumors or metastasis of brain and/or central nervous system, uncontrolled with antiepileptics and requiring high doses of steroids
  4. Known HIV positivity, active hepatitis C, or active hepatitis B
  5. Medical history of liver fibrosis/ cirrhosis
  6. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such
  7. Medical history of difficulty swallowing, malabsorption or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested product
  8. Medical history of surgery within six weeks prior to enrollment
  9. Impaired cardiac function (left ventricular ejection fraction < 45% defined by echocardiograph, serious arrhythmia, unstable angina pectoris, congestive heart failure NYHA III and IV, myocardial infarction within the last 12 months prior to trial entry; signs of pericardial effusion)
  10. Hypertension uncontrolled by standard therapies (not stabilized to 150/90 mm Hg)
  11. Peripheral neuropathy Grade >= 2
  12. Medical history of any other significant medical disease, major surgery, or psychiatric condition that might impair the subject's well being or preclude full participation in the trial
  13. Women who are pregnant or nursing
  14. Known drug abuse or alcohol abuse
  15. Participation in another clinical trial within the past 28 days
  16. Requires concurrent treatment with a non-permitted drug
  17. Known hypersensitivity to any of the trial treatment ingredients
  18. Legal incapacity or limited legal capacity
  19. Any other reason that, in the opinion of the principal investigator, precludes the subject from participating in the trial
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01014936


Locations
United States, Texas
M.D. Anderson Cancer Center
Houston, Texas, United States
Sponsors and Collaborators
EMD Serono
Merck KGaA
Investigators
Study Director: Medical Responsible EMD Serono, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany
  More Information

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT01014936     History of Changes
Other Study ID Numbers: EMR200095_001
First Submitted: November 13, 2009
First Posted: November 17, 2009
Results First Submitted: October 14, 2016
Results First Posted: April 17, 2017
Last Update Posted: August 23, 2017
Last Verified: July 2017

Keywords provided by EMD Serono:
Phase 1
advanced solid tumors
refractory to standard therapy