Trial reportCancer chemotherapy and pharmacology2011
A phase I, open-label, randomized crossover study to assess the effect of dosing of the MEK 1/2 inhibitor Selumetinib (AZD6244; ARRY-142866) in the presence and absence of food in patients with advanced solid tumors.
Trial report in Cancer chemotherapy and pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed.
- Phase II Study of Selumetinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Genetic Alterations: Arm E of the NCI-COG Pediatric MATCH Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Trial
- Effect of food on capsule and granule formulations of selumetinib.Clinical and translational science · 2022Trial
- Population Pharmacokinetics of Selumetinib and Its Metabolite N-desmethyl-selumetinib in Adult Patients With Advanced Solid Tumors and Children With Low-Grade Gliomas.CPT: pharmacometrics & systems pharmacology · 2017Trial
- Effects of cytochrome P450 (CYP3A4 and CYP2C19) inhibition and induction on the exposure of selumetinib, a MEK1/2 inhibitor, in healthy subjects: results from two clinical trials.European journal of clinical pharmacology · 2017Trial
- Combination of Gene Therapy and Chemotherapy in a New Targeted Hybrid Nanosystem to Hepatocellular Carcinoma.International journal of nanomedicine · 2024Article
- Intermittent MEK inhibition for the treatment of metastatic uveal melanoma.Frontiers in oncology · 2022Article
- Physiologically Based Pharmacokinetic Modeling for Selumetinib to Evaluate Drug-Drug Interactions and Pediatric Dose Regimens.Journal of clinical pharmacology · 2021Article
- Clinical Pharmacokinetics and Pharmacodynamics of Selumetinib.Clinical pharmacokinetics · 2021Review
- A Combined Antitumor Strategy Mediated by a New Targeted Nanosystem to Hepatocellular Carcinoma.International journal of nanomedicine · 2021Article
- Copper Chelation as Targeted Therapy in a Mouse Model of Oncogenic BRAF-Driven Papillary Thyroid Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Population pharmacokinetics of the MEK inhibitor selumetinib and its active N-desmethyl metabolite: data from 10 phase I trials.British journal of clinical pharmacology · 2018Article
- A phase I dose-escalation study of Selumetinib in combination with Erlotinib or Temsirolimus in patients with advanced solid tumors.Investigational new drugs · 2017Article
- Ex vivo treatment of patient biopsies as a novel method to assess colorectal tumour response to the MEK1/2 inhibitor, Selumetinib.Scientific reports · 2017Article
- Pharmacokinetics of a Single Oral Dose of the MEK1/2 Inhibitor Selumetinib in Subjects With End-Stage Renal Disease or Varying Degrees of Hepatic Impairment Compared With Healthy Subjects.Journal of clinical pharmacology · 2017Article
- A phase I dose-escalation study of selumetinib in combination with docetaxel or dacarbazine in patients with advanced solid tumors.BMC cancer · 2017Article
- A phase I trial of vertical inhibition of IGF signalling using cixutumumab, an anti-IGF-1R antibody, and selumetinib, an MEK 1/2 inhibitor, in advanced solid tumours.British journal of cancer · 2015Article
- Review
- Targeting RAS-ERK signalling in cancer: promises and challenges.Nature reviews. Drug discovery · 2014Review
- Profile of selumetinib and its potential in the treatment of melanoma.OncoTargets and therapy · 2014Review
- Effect of food on selumetinib pharmacokinetics and gastrointestinal tolerability in adolescents with neurofibromatosis type 1-related plexiform neurofibromas.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThis Phase I study assessed whether food influences the rate and extent of selumetinib absorption in patients with advanced solid malignancies and determined the safety, tolerability, and pharmacokinetic (PK) profile of selumetinib and its active metabolite N-desmethyl-selumetinib in fed and fasted states.
methodsA single dose of 75 mg selumetinib was to be taken with food on Day 1 followed by a single dose of 75 mg after fasting for at least 10 h on Day 8, or vice versa, followed by twice daily dosing of 75 mg selumetinib from Day 10. Plasma concentrations and PK parameters were determined on Days 1 and 8. Patients could continue to receive selumetinib for as long as they benefitted from treatment.
resultsIn total, 31 patients were randomized to receive selumetinib; 15 to fed/fasted sequence and 16 to fasted/fed sequence. Comprehensive PK sampling was performed on 11 and 10 patients, respectively. The geometric least-squares means of C(max) and AUC for selumetinib were reduced by 62% (ratio 0.38 90% CI 0.29, 0.50) and 19% (ratio 0.81 90% CI 0.74, 0.88), respectively, under fed compared with fasting conditions. The rate of absorption (t(max)) of selumetinib (fed) was delayed by approximately 2.5 h (median). The food effect was also observed for the active metabolite N-desmethyl-selumetinib. Selumetinib was well tolerated.
conclusionsThe presence of food decreased the extent of absorption of selumetinib. It is recommended that for further clinical studies, selumetinib be taken on an empty stomach. Selumetinib demonstrated an acceptable safety profile in the advanced cancer population.
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