Trial reportInvestigational new drugs2012
A comparison of the pharmacokinetics of the anticancer MET inhibitor foretinib free base tablet formulation to bisphosphate salt capsule formulation in patients with solid tumors.
Trial report in Investigational new drugs, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00742261 (An Open-label, Randomized, Two-way Balanced Crossover Study to Investigate the Bioavailability of Two Forms ofGSK1363089 in Subjects With Solid Tumors), which is not on this map. Cited by 10 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open-label, Randomized, Two-way Balanced Crossover Study to Investigate the Bioavailability of Two Forms ofGSK1363089 in Subjects With Solid Tumors
Who cites it
10 citing papers in PubMed.
- Foretinib induces G2/M cell cycle arrest, apoptosis, and invasion in human glioblastoma cells through c-MET inhibition.Cancer chemotherapy and pharmacology · 2021Article
- UPLC-MS/MS assay for quantification of an inhibitor of kinases (Foretinib) in plasma: Application to a pharmacokinetic study in rats.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2020Article
- Structural and Molecular Insight into Resistance Mechanisms of First Generation cMET Inhibitors.ACS medicinal chemistry letters · 2019Article
- Ockham's razor for the MET-driven invasive growth linking idiopathic pulmonary fibrosis and cancer.Journal of translational medicine · 2016Review
- Pharmacokinetic Aspects of Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitors.Clinical pharmacokinetics · 2016Review
- C-MET inhibitors in the treatment of lung cancer.Current treatment options in oncology · 2014Review
- Foretinib is a potent inhibitor of oncogenic ROS1 fusion proteins.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Foretinib (XL880): c-MET inhibitor with activity in papillary renal cell cancer.Current oncology reports · 2013Review
- MET inhibition in lung cancer.Translational lung cancer research · 2013Review
- MET inhibitors in combination with other therapies in non-small cell lung cancer.Translational lung cancer research · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThis phase I, open-label, randomized, 2-part crossover study assessed the safety, pharmacokinetics and relative bioavailability of single doses of the anticancer MET inhibitor foretinib (formerly known as GSK1363089, EXEL-2880 and XL-880) free base tablet formulation compared to a bisphosphate salt capsule formulation (Part 1), and assessed the safety, efficacy, and pharmacokinetics of the bisphosphate salt capsule administered 3 times a week in cancer patients (Part 2). PATIENTS AND
methodsIn Part 1, patients were randomized in a crossover manner to receive a single oral dose of foretinib formulated as a bisphosphate salt capsule (240 mg; 183 mg free base equivalent) followed one week later by a single dose of a free base tablet (180 mg), or vice versa where the treatment sequence was reversed. In Part 2, patients self-administered oral doses of bisphosphate salt capsules (200 mg) 3 times a week until disease progression.
resultsTwelve patients with solid tumors were enrolled and completed Part 1, and 10 patients continued into Part 2. Most AEs were mild or moderate in severity. The most common drug-related AEs were fatigue, diarrhea, and nausea. The least-squares (LS) mean total area under the curve was 3144 and 3514 ng*h/mL for the free base tablet and bisphosphate salt capsule, respectively, with a ratio of 0.89 (90% confidence interval, CI: 0.69, 1.16). The LS mean maximal concentration (Cmax) was 81.6 and 98.5 ng/mL for the free base and bisphosphate salt, respectively, with a ratio of 0.83 (90% confidence interval, CI: 0.67, 1.02). The time to reach Cmax was ∼4 h for both formulations. The pharmacokinetics of foretinib were not clinically different between the 2 formulations. Of the 10 patients assessed for efficacy, 3 patients achieved stable disease.
conclusionsForetinib was well tolerated as single doses of both the free base and bisphosphate salt formulations. The pharmacokinetics and relative bioavailability of the 2 formulations were not clinically different. The bisphosphate salt formulation was well tolerated on a 3-times a week dosing schedule, and reached steady-state plasma concentration after 2 weeks.
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