A phase 1 study of eribulin mesylate (E7389), a novel microtubule-targeting chemotherapeutic agent, in children with refractory or recurrent solid tumors: A Children's Oncology Group Phase 1 Consortium study (ADVL1314).

Background: Eribulin mesylate is a novel anticancer agent that inhibits microtubule growth, without effects on shortening, and promotes nonproductive tubulin aggregate formation. We performed a phase 1 trial to determine the dose-limiting toxicities (DLTs), maximum tolerated or recommended phase 2 dose (MTD/RP2D), and pharmacokinetics (PK) of eribulin in children with refractory or recurrent solid (excluding central nervous system) tumors.

Methods: Eribulin was administered intravenously on days 1 and 8 in 21-day cycles.

Effects of Ketoconazole on the Pharmacokinetics of Lenvatinib (E7080) in Healthy Participants.

Background: Lenvatinib is an oral, multitargeted, tyrosine kinase inhibitor under clinical investigation in solid tumors. In vitro evidence indicates that lenvatinib metabolism may be modulated by ketoconazole, an inhibitor of CYP3A4 and p-glycoprotein.

Methods: In this Phase I, single-center, randomized, open-label, two-period, crossover study, healthy adults (18-55 years; N = 18) were randomized to one of two sequences (ketoconazole → placebo or vice versa).

A randomized, three-treatment, three-period, six-sequence-crossover, single-center, bioequivalence study to evaluate the impact of different 10-mg crystalline forms on the pharmacokinetics of lenvatinib in healthy volunteers.

Objective: This study assessed the impact of varying lenvatinib crystalline forms in 10-mg lenvatinib capsules on drug bioavailability in healthy volunteers.

Materials: Lenvatinib 10-mg capsules (low C and high C forms).

Methods: This randomized, three-period- crossover study compared the pharmacokinetics and safety of two crystalline forms of capsules (low C-form, <4% crystalline; high C-form, 38% crystalline) to a standard (ref Cform, 15% crystalline).

Influence of hepatic impairment on lenvatinib pharmacokinetics following single-dose oral administration.

This open-label, single-dose study assessed lenvatinib pharmacokinetics (PK) in subjects with normal hepatic function (n = 8) and mild, moderate, or severe hepatic impairment (n = 6 each). Subjects received 10 mg oral lenvatinib, except those with severe hepatic impairment (5 mg). Plasma and urine samples were collected over 14 days; free and total lenvatinib and its metabolites were analyzed using validated chromatography/spectrometry.

Effect of rifampicin on the pharmacokinetics of lenvatinib in healthy adults.

Background And Objectives: Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor under clinical investigation in solid tumours. This study evaluated the influence of P-glycoprotein (P-gp) inhibition (single-dose rifampicin) and simultaneous cytochrome P450 3A4 (CYP3A4)/P-gp induction (multiple-dose rifampicin) on lenvatinib pharmacokinetics.

Methods: This Phase I, single-centre, single-dose (lenvatinib mesylate 24 mg), open-label, sequential study enrolled 15 healthy volunteers.

Effect of lenvatinib (E7080) on the QTc interval: results from a thorough QT study in healthy volunteers.

Purpose: QT assessment of oncology drugs is generally challenging because they are genotoxic and, of necessity,they require multisite evaluation in cancer patients. Lenvatinib is not genotoxic, therefore, this thorough QT (TQT)study with lenvatinib, a multityrosine kinase inhibitor, was undertaken utilizing healthy volunteers and concentration effect modeling to project the TQT effect at high plasma levels.

Methods: Fifty-two healthy subjects randomly received single doses of lenvatinib 32 mg, placebo, or moxifloxacin 400 mg in a three-way crossover study.

Evaluation of the effects of formulation and food on the pharmacokinetics of lenvatinib (E7080) in healthy volunteers.

Objective: To evaluate the effect of formulation and a high-fat meal on the pharmacokinetics of orally administered lenvatinib (E7080).

Materials: Lenvatinib 10-mg capsule and tablet.

Methods: Pharmacokinetics and safety of a single 10-mg lenvatinib dose were evaluated in healthy subjects in two randomized, two-period, crossover, phase 1, bioavailability trials.