A Multicentre, Open Label, Phase I Trial in Japan of the MEK Inhibitor Pimasertib Given Orally to Subjects With Solid Tumors as Monotherapy
This is a two-part trial. "Solid tumor" in this protocol means solid tumor excluding hepatocellular carcinoma (HCC).
Part 1: Dose Escalation Phase in subjects with solid tumor (Cohort A) and HCC (Cohort B). The dose will be increased from 45 mg twice a day (BID) with 3+3 cohort method up to the recommended phase 2 dose (RP2D) of pimasertib established as single agent in the global studies for each arm independently.
Part 2: The Maximum Tolerated Dose (MTD) defined in Part 1 will be confirmed in more subjects in Cohort A (N=18) and Cohort B (N=6) separately.
Advanced Solid Tumors
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Multicentre, Open Label, Phase I Trial in Japan of the MEK Inhibitor Pimasertib Given Orally to Subjects With Solid Tumors as Monotherapy|
- Number of Participants Who Experienced at least one Dose Limiting Toxicity (DLT) During Treatment Cycle 1 (days 1-21) by arm and treatment level [ Time Frame: Days 1-21 ] [ Designated as safety issue: Yes ]
- Number of participants who experienced treatment-emergent adverse events (TEAEs) [ Time Frame: Day 1 up to approximately Day 84 (end of cycle 4) ] [ Designated as safety issue: Yes ]
- Pharmacokinetic parameters [ Time Frame: Day 1 up to approximately Day 84 (end of cycle 4) ] [ Designated as safety issue: No ]Maximum concentration (Cmax), time to maximum concentration (tmax), area under the curve from hours 0-24 (AUC0-24), area under the curve over time (AUCt), apparent terminal half-life (t1/2), apparent clearance (CL/f), apparent clearance at steady-state (CLss/f), apparent volume of distribution at terminal phase (Vz/f), apparent volume of distribution at steady-state (Vss/f), accumulation ratio for AUC (Racc(AUC)), accumulation ratio for Cmax (Racc(Cmax))
- Participants best overall response as Assessed by the Investigator [ Time Frame: Day 1 up to approximately Day 84 (end of cycle 4) ] [ Designated as safety issue: No ]
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||February 2014|
|Estimated Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Pimasertib taken as assigned in doses between the 45 mg twice a day (BID) up to the recommended phase 2 dose (RP2D) expected to be between 60-75mg BID.
Pimasertib will be supplied as 15 and 30 mg hard gelatin capsules. Pimasertib will be taken orally twice a day continuously. Treatment will be administered in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01668017
|Contact: Yukito Kuwahara, Clinical Trial Leaderemail@example.com|
|Merck Serono Co., Ltd for recruiting locations in, Japan|
|Principal Investigator:||Department of GI Oncology/Gastroenterology||National Cancer Centre Hospital East|