title: Phase I single dose, two-period and two-sequence cross-over trial to evaluate the relative bioavailability of two oral pimasertib formulations in advanced cancer patients.
abstract: A phase I two-period two sequence cross-over study compared the bioavailability of two pimasertib (MSC1936369B/AS703026) formulations (capsule versus tablet) in advanced cancer patients.
  
  
  
  Patients with advanced solid tumors were randomized to one of two treatment sequences utilizing pimasertib tablet (test; 3 × 20 mg, PO QD) and capsule (standard; 2 × 30 mg, PO QD). The trial comprised a screening and baseline period, two time periods or parts A and B, and a trial extension phase.
  
  
  
  N = 38 patients were randomized to two treatment sequences S1 and S2. PK parameters t1/2, CL/f, and Vz/f were within the same range for the two formulations. Tablet had bioavailability comparable to capsule based on the analysis of AUC0-t, however, tablet administration resulted in an increase of ~25% in Cmaxversus capsule. Common predicted adverse events of pimasertib included ocular events, diarrhea and creatine phosphokinase elevation. Disease control rate was ~29% with 1 partial response and 4 of 10 patients with stable disease >4 months.
  
  
  
  Pimasertib tablet was overall well tolerated, had a similar safety and efficacy profile to standard capsule formulation and had bioavailability comparable to capsule.
authors.affiliation: University of Arizona Cancer Center, 1515, N. Campbell Avenue, Tucson, AZ, 85724, USA. dmahadevan@uacc.arizona.edu.
authors.forename: D
authors.identifier: 0000-0002-2991-0361
authors.initials: D
authors.lastname: Mahadevan
authors.affiliation: Cedars Sinai Medical Center, 8737 Beverly Blvd. # 203, Los Angeles, CA, 90048, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Mita
authors.affiliation: Texas Oncology-Tyler, US Oncology Research, 910 E. Houston Street, Suite 100, Tyler, TX, 75702, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Richards
authors.affiliation: California Cancer Associates for Research & Excellence, Inc., 7675 Dagget Street, Suite 370, San Diego, CA, 92111, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: McClay
authors.affiliation: Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
authors.forename: Rebecca Suk
authors.initials: RS
authors.lastname: Heist
authors.affiliation: University of Arizona Cancer Center, 1515, N. Campbell Avenue, Tucson, AZ, 85724, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.affiliation: University of Arizona Cancer Center, 1515, N. Campbell Avenue, Tucson, AZ, 85724, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sundararajan
authors.affiliation: Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, University of Texas M. D. Anderson Cancer Center-Investigational Cancer Therapeutics, 1515 Holcombe Blvd. Unit 455, Huston, TX, 77030, USA.
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D018592:Cross-Over Studies; D004339:Drug Compounding; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013607:Tablets; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002214:Capsules; C550600:N-(2,3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamide; D047428:Protein Kinase Inhibitors; D013607:Tablets; D009536:Niacinamide
keywords: Bioavailability; Capsule and tablet formulation; MEK 1/2 inhibitor; Pimasertib