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.
|Contact: Yukito Kuwahara, Clinical Trial Leaderfirstname.lastname@example.org|
|Merck Serono Co., Ltd for recruiting locations in, Japan|
|Principal Investigator:||Department of GI Oncology/Gastroenterology||National Cancer Centre Hospital East|