Overview

This trial has been completed.

Conditions solid tumors, cancer
Treatments msc1936369b
Phase phase 1
Sponsor Merck KGaA
Collaborator Merck Serono S.A., Geneva
Start date December 2007
End date March 2013
Trial size 180 participants
Trial identifier NCT00982865, 2007-004665-18, 28062

Summary

This is a first in man trial with a primary objective being the determination of the Maximum Tolerated dose (MTD) and the dose-limiting toxicity (DLT) in several regimens of MEK inhibitor MSC1936369B administered orally once a day, in subjects with malignant solid tumors to see how safe is treatment with MSC1936369B.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation non-randomized
Intervention model parallel assignment
Primary purpose treatment
Masking no masking
Arm
(Experimental)
Orally once daily on Days 1 to 5, 8 to 12 and 15 to 19 of a 21-day cycle.
msc1936369b Pimasertib
MSC1936369B will be administered to subjects at a dose of 1 to 120 milligram (mg) at escalating dose levels once daily up to 2 cycles (Each cycle of 21 days) and if the subject will be treated beyond 2 cycles the treatment continues until progressive disease or intolerable toxicity or investigator/subject decision.
(Experimental)
Orally once a day on Days 1 to 15 of a 21-day cycle. Orally once a day from Day 1 to 21.
msc1936369b Pimasertib
MSC1936369B will be administered to subjects at a dose of 1 to 255 mg at escalating dose levels once daily up to 2 cycles (Each cycle of 21 days) and if the subject will be treated beyond 2 cycles the treatment continues until progressive disease or intolerable toxicity or investigator/subject decision.
msc1936369b Pimasertib
Subjects in the regimen 2 food effect cohort will be sequentially assigned in a 1:1 ratio to either the fed/fasted sequence or fasted/fed sequence for Day 1 of Cycle 1 and Cycle 2. Subjects will be administered with MSC1936369B at a dose of 90-150 mg at escalating dose levels once daily up to 2 cycles (Each cycle of 21 days) and if the subject will be treated beyond 2 cycles the treatment continues until progressive disease or intolerable toxicity or investigator/subject decision.
(Experimental)
Orally once a day from Day 1 to 21.
msc1936369b Pimasertib
MSC1936369B will be administered to subjects at a dose of 60 to 90 mg at escalating dose levels once daily up to 2 cycles (Each cycle of 21 days) and if the subject will be treated beyond 2 cycles the treatment continues until progressive disease or intolerable toxicity or investigator/subject decision.
(Experimental)
Orally twice a day from either Days 1 to 15 of a 21-day cycle (similar to Regimen 2) or up to Day 21 (similar to Regimen 3).
msc1936369b Pimasertib
MSC1936369B will be administered to subjects at a dose of 45 to 75 mg at escalating dose levels once daily up to 2 cycles (Each cycle of 21 days) and if the subject will be treated beyond 2 cycles the treatment continues until progressive disease or intolerable toxicity or investigator/subject decision.

Primary Outcomes

Measure
Number of subjects experienced at least a Dose-Limiting Toxicity (DLT) over the first cycle - Day 1 to 21
time frame: 21 days

Secondary Outcomes

Measure
Number of subjects experienced treatment-emergent adverse events (TEAE), serious TEAEs, TEAEs leading to discontinuation and TEAEs leading to death
time frame: From the first dose of study drug administration up to 30+/-3 days after the last dose of study drug administration
Number of subjects experienced clinically significant changes in laboratory parameters and/or vital signs judged to be related to the trial medication
time frame: From the date of randomization up to end of the treatment , assessed up to 5.4 years
Maximum observed plasma concentration of pimasertib
time frame: Cycle1:Reg1,2,3:Day1(Cycle 2,3),Day12(reg1);Day15(reg 2,3):Pre-dose,0.5,1,1.5,2, 2.5,4,6,8hours post-dose.Day 2:Pre-dose;Day3,8:Pre-dose,1 and 4 hours post-dose;Cycle 2 Day1:12hours post-dose;Day 2:Pre-dose(reg2 FE cohort);Cycle4+,Reg 1,2,3:Day1:Pre-dose
Time to reach maximum plasma concentration of pimasertib
time frame: Cycle1:Reg1,2,3:Day1(Cycle 2,3),Day12(reg1);Day15(reg 2,3):Pre-dose,0.5,1,1.5,2, 2.5,4,6,8hours post-dose.Day 2:Pre-dose;Day3,8:Pre-dose,1 and 4 hours post-dose;Cycle 2 Day1:12hours post-dose;Day 2:Pre-dose(reg2 FE cohort);Cycle4+,Reg 1,2,3:Day1:Pre-dose
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of pimasertib
time frame: Cycle1:Reg1,2,3:Day1(Cycle 2,3),Day12(reg1);Day15(reg 2,3):Pre-dose,0.5,1,1.5,2, 2.5,4,6,8hours post-dose.Day 2:Pre-dose;Day3,8:Pre-dose,1 and 4 hours post-dose;Cycle 2 Day1:12hours post-dose;Day 2:Pre-dose(reg2 FE cohort);Cycle4+,Reg 1,2,3:Day1:Pre-dose
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of pimasertib
time frame: Cycle1:Reg1,2,3:Day1(Cycle 2,3),Day12(reg1);Day15(reg 2,3):Pre-dose,0.5,1,1.5,2, 2.5,4,6,8hours post-dose.Day 2:Pre-dose;Day3,8:Pre-dose,1 and 4 hours post-dose;Cycle 2 Day1:12hours post-dose;Day 2:Pre-dose(reg2 FE cohort);Cycle4+,Reg 1,2,3:Day1:Pre-dose
Apparent terminal half life of pimasertib
time frame: Cycle1:Reg1,2,3:Day1(Cycle 2,3),Day12(reg1);Day15(reg 2,3):Pre-dose,0.5,1,1.5,2, 2.5,4,6,8hours post-dose.Day 2:Pre-dose;Day3,8:Pre-dose,1 and 4 hours post-dose;Cycle 2 Day1:12hours post-dose;Day 2:Pre-dose(reg2 FE cohort);Cycle4+,Reg 1,2,3:Day1:Pre-dose

Eligibility Criteria

All participants at least 18 years old.

Inclusion Criteria: - Pathologically-confirmed solid tumor which is locally advanced or metastatic, and either refractory after standard therapy for the disease or for which no effective standard therapy is available. In the regimen 3, regimen 2 food-effect, and BID cohorts, the tumor type will be restricted to melanoma. - Age greater than or equal to (>=) 18 years - Has read and understands the informed consent form and is willing and able to give informed consent. Fully understands requirements of the trial and willing to comply with all trial visits and assessments Exclusion Criteria: - Bone marrow impairment as evidenced by Haemoglobin less than (<) 9.0 gram per deciliter (g/dL), Neutrophil count < 1.0 x 10^9/Liter, platelets < 100 x 10^9/Liter - Renal impairment as evidenced by serum creatinine > 1.5 x upper limit normal (ULN), and/or calculated creatinine clearance < 60 milliliter per minute (mL/min) - Liver function abnormality as defined by total bilirubin > 1.5 x ULN, or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2.5 x ULN, for subjects with liver involvement AST/ALT > 5 x ULN - INR > 1.5 x ULN - Serum calcium > 1 x ULN - History of central nervous system (CNS) metastases, unless subject has been previously treated for CNS metastases, is stable by computer tomography (CT) scan without evidence of cerebral oedema, and has no requirements for corticosteroids or anticonvulsants - History of difficulty swallowing, malabsorption or other chronic gastro-intestinal disease or conditions that may hamper compliance and/or absorption of the tested product - Eastern Cooperative Oncology Group Performance status (ECOG PS) greater than (>) 1 - Known human immunodeficiency virus (HIV) positivity, active hepatitis C, or active hepatitis B

Additional Information

Official title A Multicenter, Open Label, Phase I Trial of the MEK Inhibitor MSC1936369B Given Orally to Subjects With Solid Tumours
Trial information was received from ClinicalTrials.gov and was last updated in February 2017.
Information provided to ClinicalTrials.gov by Merck KGaA.