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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00982865




Trial ID
NCT00982865
Ethics application status
Date submitted
22/09/2009
Date registered
22/09/2009
Date last updated
12/02/2017

Titles & IDs
Public title
Trial of MSC1936369B in Subjects With Solid Tumors
Scientific title
A Multicenter, Open Label, Phase I Trial of the MEK Inhibitor MSC1936369B Given Orally to Subjects With Solid Tumours
Secondary ID [1] 0 0
2007-004665-18
Secondary ID [2] 0 0
28062
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors 0 0
Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MSC1936369B
Treatment: Drugs - MSC1936369B
Treatment: Drugs - MSC1936369B
Treatment: Drugs - MSC1936369B
Treatment: Drugs - MSC1936369B

Experimental: MSC1936369B Regimen 1 - Orally once daily on Days 1 to 5, 8 to 12 and 15 to 19 of a 21-day cycle.

Experimental: MSC1936369B Regimen 2 and Regimen 2 Food Effect - Orally once a day on Days 1 to 15 of a 21-day cycle.
Orally once a day from Day 1 to 21.

Experimental: MSC1936369B Regimen 3 once daily - Orally once a day from Day 1 to 21.

Experimental: MSC1936369B Regimen 3 twice daily - 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).


Treatment: Drugs: MSC1936369B
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.

Treatment: Drugs: MSC1936369B
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.

Treatment: Drugs: MSC1936369B
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.

Treatment: Drugs: MSC1936369B
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.

Treatment: Drugs: MSC1936369B
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of subjects experienced at least a Dose-Limiting Toxicity (DLT) over the first cycle - Day 1 to 21 - DLT was defined using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 (CTCAE), as any of the following toxicities at any dose level and judged to be possibly or probably related to the trial medication by the investigator and/or the sponsor: any Grade 3 or more non-haematological toxicity excluding: Grade 3 asymptomatic increase in liver function tests reversible within 7 days for subjects without liver involvement, or Grade 4 for subjects with liver involvement. Grade 3 vomiting if it is encountered despite adequate and optimal therapy (e.g. 5HT3 antagonists and corticosteroids). Grade 3 diarrhoea if it is encountered despite adequate and optimal anti diarrhoea therapy. Any Grade 4 neutropenia of > 5 days duration or febrile neutropenia lasting for more than 1 day. Grade 4 thrombocytopenia > 1 day or Grade 3 with bleeding. Any treatment delay > 2 weeks due to drug-related adverse effects.
Timepoint [1] 0 0
21 days
Secondary outcome [1] 0 0
Number of subjects experienced treatment-emergent adverse events (TEAE), serious TEAEs, TEAEs leading to discontinuation and TEAEs leading to death
Timepoint [1] 0 0
From the first dose of study drug administration up to 30+/-3 days after the last dose of study drug administration
Secondary outcome [2] 0 0
Number of subjects experienced clinically significant changes in laboratory parameters and/or vital signs judged to be related to the trial medication
Timepoint [2] 0 0
From the date of randomization up to end of the treatment , assessed up to 5.4 years
Secondary outcome [3] 0 0
Maximum observed plasma concentration of pimasertib
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Time to reach maximum plasma concentration of pimasertib
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of pimasertib
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
Apparent terminal half life of pimasertib
Timepoint [7] 0 0
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
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Brussels
Country [2] 0 0
Belgium
State/province [2] 0 0
Ghent
Country [3] 0 0
France
State/province [3] 0 0
Bordeaux
Country [4] 0 0
France
State/province [4] 0 0
Paris
Country [5] 0 0
France
State/province [5] 0 0
Rennes
Country [6] 0 0
France
State/province [6] 0 0
Toulouse
Country [7] 0 0
Netherlands
State/province [7] 0 0
Amsterdam

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck KGaA
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Serono S.A., Geneva
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT00982865
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
Merck KGaA
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries