A5075037954- Cancer Treatment and Pharmacology
- Protein Kinase Regulation and GTPase Signaling
- Chronic Myeloid Leukemia Treatments
- PI3K/AKT/mTOR signaling in cancer
- Nanoparticle-Based Drug Delivery
- Lung Cancer Research Studies
- Cancer therapeutics and mechanisms
- Radiopharmaceutical Chemistry and Applications
- Chronic Lymphocytic Leukemia Research
- HER2/EGFR in Cancer Research
- Hepatocellular Carcinoma Treatment and Prognosis
- Neutropenia and Cancer Infections
- Glioma Diagnosis and Treatment
- PARP inhibition in cancer therapy
- Cancer, Lipids, and Metabolism
- Cancer Research and Treatment
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Sarcoma Diagnosis and Treatment
- Chemotherapy-related skin toxicity
- Cancer Genomics and Diagnostics
- Peptidase Inhibition and Analysis
- Gastrointestinal Tumor Research and Treatment
- Colorectal Cancer Treatments and Studies
- Lanthanide and Transition Metal Complexes
- Neuroendocrine Tumor Research Advances
Erasmus MC Cancer Institute
2017-2025
Amphia Ziekenhuis
2024
Erasmus MC
2017-2019
Erasmus University Rotterdam
2017
Amsterdam UMC Location University of Amsterdam
2011
University of Amsterdam
2011
Abstract Purpose: CPC634 is a novel nanoparticle entrapping docetaxel, developed to enhance the intratumoral chemotherapy exposure. This randomized cross-over study compared and plasma pharmacokinetics of with conventional docetaxel. Patients Methods: Adult patients solid tumors were receive (75 mg/m2) in cycle 1, docetaxel 2 or vice versa. The was powered identify 25% increase total exposure after infusion Four allocated per tumor sampling time point, that is, 24, 48, 72, 96 hours, 7 14...
Background: CPC634 is docetaxel entrapped in core-cross linked polymeric micelles. In preclinical studies, demonstrated enhanced pharmacokinetics and improved therapeutic index. This phase I dose escalation study the first-in-human with CPC634. Methods: adult patients advanced solid tumours received intravenously either 3-weekly (Q3W) (part 1, range 15–100 mg/m2), 2-weekly (Q2W) 2, 45 mg/m2) or Q3W dexamethasone premedication 3, 60 mg/m2). Results: thirty-three were enrolled. Skin toxicity...
This study examined safety, pharmacokinetics, and efficacy of veliparib, a PARP inhibitor, combined with carboplatin etoposide in patients extensive-stage (ED) small cell lung cancer (SCLC) other solid tumors.The 3 + design was used for dose escalation oral veliparib combination (AUC 5 on day 1) (100 mg/m2 days 1-3) 21-day cycles. Veliparib explored from 80 to 240 mg b.i.d. 7-day, 14-day, or continuous schedules. Patients without disease progression continued maintenance monotherapy...
Abstract Purpose: Monopolar spindle 1 (MPS1) kinase inhibitor, BAY 1217389 (BAY) synergizes with paclitaxel. This phase I study assessed the combination of paclitaxel using a novel randomized continuous reassessment method (rCRM) to improve dose determination. Patients and Methods: solid tumors were receive oral (twice daily 2-days-on/5-days-off) weekly (90 mg/m2) or monotherapy in cycle 1. Dose escalation was guided by CRM modeling. Primary objectives assess safety, establish MTD BAY,...
AimsBrugada syndrome (BrS) is associated with increased risk for atrial fibrillation (AFib). However, the role of SCN5A mutations in occurrence AFib remains unclear. Cardiac sodium current reduction caused by may facilitate slowing intra-atrial conduction and inducing structural changes, but also prevent it suppressing ectopic activity. Here, we examined relation between mutations, velocity, activity BrS.
Gastrointestinal stromal tumors (GISTs) are characterized by oncogenic KIT mutations that cluster in two exon 11 hotspots. The aim of this study was to develop a single, sensitive, quantitative digital droplet PCR (ddPCR) assay for the detection common both GIST tumor tissue and circulating DNA (ctDNA) isolated from patients' plasma.A ddPCR designed using probes cover Available archival FFPE 27 consecutive patients with known 9 randomly selected without were tested. Plasma samples...
The mammalian target of rapamycin (mTOR) inhibitor everolimus is used in the treatment breast cancer, neuroendocrine tumors, and renal cancer. approved 10 mg once-daily dose associated with considerable adverse effects it has been suggested that these are maximum concentration (C max) everolimus. Twice-daily dosing might be an alternative strategy improved tolerability; however, a direct pharmacokinetic comparison 5 twice-daily lacking.We performed prospective, randomized, pharmacokinetic,...
3026 Background: CPC634 is a novel product with docetaxel temporarily entrapped within stabilized CriPec nanoparticles. We performed the first-in-human study (NCT02442531). Methods: Patients (≥18 years) received intravenously either 3-weekly (Q3W) (part 1, 15-100 mg/m 2 ), 2-weekly (Q2W) 2, 45 ) or Q3W dexamethasone premedication 3) following 3+3 design. Primary objectives were to assess safety, establish maximum tolerated dose (MTD), recommended phase (RP2D), and evaluate pharmacokinetic...
Docetaxel entrapped nanoparticle CPC634 is associated with dose-related skin toxicity that resembles conventional docetaxel (Cd)-related toxicity. This study compared the cutaneous pharmacokinetics and pharmacodynamics of CPC634. In this randomised cross-over study, patients solid tumours received one cycle Cd (both at 75 mg/m2). Skin biopsies were taken baseline day 8 both cycles. Released total (released plus docetaxel) concentrations histopathological changes in evaluated. Twenty...
8530 Background: The majority of SCLC cases are diagnosed as ED, for which there is a poor prognosis and no curative treatment (Tx). V, potent PARP inhibitor, has been shown in preclinical studies to enhance the antitumor activity platinum-based agents E against SCLC. presented phase 1 dose-escalation (NCT02289690) evaluated V combined with Cb/E. Methods: Pts (≥18 years) ED or other advanced/metastatic solid tumors ≤1 line prior cytotoxic therapy ECOG performance score 0/1 were included....
Abstract Introduction Gastrointestinal stromal tumors (GISTs) are rare malignancies of the gastrointestinal tract. In Netherlands, most patients with GIST treated in five sarcoma expertise centers. is known to have driver mutations tyrosine kinase receptors KIT and PDGFRα respectively 80% 10% patients. Mutations (single nucleotide variations, insertions deletions) mostly found exon 9 11. a primary 11 mutation respond generally well inhibitors (TKIs). The aim this study was evaluate treatment...
3096 Background: Failure or resistance to chemotherapy may be caused by sub‐therapeutic intratumoral drug levels. Nanomedicine aim improve exposure. CPC634 is a nanoparticle entrapping docetaxel. We hypothesized that increases docetaxel Methods: In this randomized cross-over study we assessed and plasma pharmacokinetics (PK) of after intravenous administration conventional (Cd). The was powered identify an 25% increase in exposure relative Cd. Patients (≥18 years) were receive 75 mg/m 2...
<div>AbstractPurpose:<p>Monopolar spindle 1 (MPS1) kinase inhibitor, BAY 1217389 (BAY) synergizes with paclitaxel. This phase I study assessed the combination of paclitaxel using a novel randomized continuous reassessment method (rCRM) to improve dose determination.</p>Patients and Methods:<p>Patients solid tumors were receive oral (twice daily 2-days-on/5-days-off) weekly (90 mg/m<sup>2</sup>) or monotherapy in cycle 1. Dose escalation was guided by CRM...
Supplementary Data from A Phase I Study of an MPS1 Inhibitor (BAY 1217389) in Combination with Paclitaxel Using a Novel Randomized Continual Reassessment Method for Dose Escalation
Supplementary Data from A Phase I Study of an MPS1 Inhibitor (BAY 1217389) in Combination with Paclitaxel Using a Novel Randomized Continual Reassessment Method for Dose Escalation