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Results: 17
A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma.
Peter E Hall, Rachel Lewis, Nelofer Syed, Richard Shaffer, Jane Evanson, Stephen Ellis, Matthew Williams, Xiaoxing Feng, Amanda Johnston, Jim A Thomson, Fiona P Harris, Raj Jena, Tomasz Matys, Sarah Jefferies, Kate Smith, Bor-Wen Wu, John S Bomalaski, Timothy Crook, Kevin O'Neill, Dimitris Paraskevopoulos, Ramsay S Khadeir, Michael Sheaff, Simon Pacey, Piers N Plowman, Peter W Szlosarek
Sep 19, 2019
PURPOSE: Patients with recurrent high-grade gliomas (HGG) are usually managed with alkylating chemotherapy ± bevacizumab. However, prognosis remains very poor. Preclinically, we showed that HGGs are a target for arginine...
Adult Antineoplastic Combined Chemotherapy Protocols Arginine Argininosuccinate Synthase Brain Neoplasms cisplatin Female Follow-Up Studies glioma Humans Hydrolases Male Maximum Tolerated Dose Middle Aged Neoplasm Grading Neoplasm Recurrence Local Pemetrexed Polyethylene Glycols Retrospective Studies Tissue Distribution Treatment Outcome
Practical recommendations for implementing a Bayesian adaptive phase I design during a pandemic.
BACKGROUND: Modern designs for dose-finding studies (e.g., model-based designs such as continual reassessment method) have been shown to substantially improve the ability to determine a suitable dose for efficacy testing when...
A First-in-Human Study of the New Oral Selective Estrogen Receptor Degrader AZD9496 for ER+/HER2- Advanced Breast Cancer.
Erika P Hamilton, Manish R Patel, Anne C Armstrong, Richard D Baird, Komal Jhaveri, Matthias Hoch, Teresa Klinowska, Justin PO Lindemann, Shethah R Morgan, Gaia Schiavon, Hazel M Weir, Seock-Ah Im
Jul 27, 2018
Purpose: AZD9496 is an oral nonsteroidal, small-molecule inhibitor of estrogen receptor alpha (ERα) and a potent and selective antagonist and degrader of ERα. This first-in-human phase I study determined the safety and...
Adult Aged Aged 80 and over Biomarkers Tumor Breast Neoplasms Cinnamates Dose-Response Relationship Drug Drug-Related Side Effects and Adverse Reactions Estrogen Receptor alpha Female Humans Indoles Maximum Tolerated Dose Middle Aged Nausea Protein Kinase Inhibitors Receptor ErbB-2 Selective Estrogen Receptor Modulators
First-in-human phase I study of pictilisib (GDC-0941), a potent pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, in patients with advanced solid tumors.
Debashis Sarker, Joo Ern Ang, Richard Baird, Rebecca Kristeleit, Krunal Shah, Victor Moreno, Paul A Clarke, Florence I Raynaud, Gallia Levy, Joseph A Ware, Kathryn Mazina, Ray Lin, Jenny Wu, Jill Fredrickson, Jill M Spoerke, Mark R Lackner, Yibing Yan, Lori S Friedman, Stan B Kaye, Mika K Derynck, Paul Workman, Johann S de Bono
Jan 26, 2015
Administration Oral Adult Aged Dose-Response Relationship Drug Drug-Related Side Effects and Adverse Reactions Female Humans Indazoles Male Maximum Tolerated Dose Middle Aged Neoplasms Phosphatidylinositol 3-Kinases Phosphoinositide-3 Kinase Inhibitors Protein Kinase Inhibitors Proto-Oncogene Proteins B-raf Sulfonamides
A phase I and pharmacological study of the matrix metalloproteinase inhibitor BB-3644 in patients with solid tumours.
BB-3644 is an oral, broad-spectrum matrix metalloproteinase inhibitor (MMPI) structurally related to marimastat and BB-94. It is also >10-fold more active than marimastat in inhibiting the processing of cell-bound TNF-alpha....
Using an Interaction Parameter in Model-Based Phase I Trials for Combination Treatments? A Simulation Study.
There is growing interest in Phase I dose-finding studies studying several doses of more than one agent simultaneously. A number of combination dose-finding designs were recently proposed to guide escalation/de-escalation...
Evaluation of rodent-only toxicology for early clinical trials with novel cancer therapeutics.
Preclinical toxicology studies are performed prior to phase I trials with novel cancer therapeutics to identify a safe clinical starting dose and potential human toxicities. The primary aim of this study was to evaluate the...
How to design a dose-finding study using the continual reassessment method.
Graham M Wheeler, Adrian P Mander, Alun Bedding, Kristian Brock, Victoria Cornelius, Andrew P Grieve, Thomas Jaki, Sharon B Love, Lang'o Odondi, Christopher J Weir, Christina Yap, Simon J Bond
Feb 25, 2019
INTRODUCTION: The continual reassessment method (CRM) is a model-based design for phase I trials, which aims to find the maximum tolerated dose (MTD) of a new therapy. The CRM has been shown to be more accurate in targeting the...
Valproic acid disables the Nrf2 anti-oxidant response in acute myeloid leukaemia cells enhancing reactive oxygen species-mediated killing.
Yao Jiang, Andrew D Southam, Sandro Trova, Flavio Beke, Bader Alhazmi, Thomas Francis, Anshul Radotra, Alessandro di Maio, Mark T Drayson, Chris M Bunce, Farhat L Khanim
Jan 28, 2022
BACKGROUND: We previously demonstrated the in vitro killing of AML cells by the combination of the lipid-lowering agent bezafibrate (BEZ) and the contraceptive hormone medroxyprogesterone acetate (MPA). A phase II trial...
Dose finding studies for therapies with late-onset toxicities
An objective of phase I dose-finding trials is to find the maximum tolerated dose; the dose with a particular risk of toxicity. Frequently, this risk is assessed across the first cycle of therapy. However, in oncology, a course...
Phase I clinical trial repurposing all-trans retinoic acid as a stromal targeting agent for pancreatic cancer.
Hemant M Kocher, Bristi Basu, Fieke EM Froeling, Debashis Sarker, Sarah Slater, Dominic Carlin, Nandita M deSouza, Katja N De Paepe, Michelle R Goulart, Christine Hughes, Ahmet Imrali, Rhiannon Roberts, Maria Pawula, Richard Houghton, Cheryl Lawrence, Yathushan Yogeswaran, Kelly Mousa, Carike Coetzee, Peter Sasieni, Aaron Prendergast, David J Propper
Sep 25, 2020
A dose-finding design for dual-agent trials with patient-specific doses for one agent with application to an opiate detoxification trial.
There is a growing interest in early phase dose-finding clinical trials studying combinations of several treatments. While the majority of dose finding designs for such setting were proposed for oncology trials, the...
Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers.
Timothy A Yap, Li Yan, Amita Patnaik, Nina Tunariu, Andrea Biondo, Ivy Fearen, Kyriakos P Papadopoulos, David Olmos, Richard Baird, Liliana Delgado, Ernestina Tetteh, Robert A Beckman, Lisa Lupinacci, Ruth Riisnaes, Shaun Decordova, Simon P Heaton, Karen Swales, Nandita M deSouza, Martin O Leach, Michelle D Garrett, Daniel M Sullivan, Johann S de Bono, Anthony W Tolcher
Jan 26, 2015
Adult Aged Antineoplastic Agents Biomarkers Diagnostic Imaging Drug Administration Schedule Drug Monitoring Female Heterocyclic Compounds 3-Ring Humans Magnetic Resonance Imaging Male Maximum Tolerated Dose Middle Aged Neoplasm Staging Neoplasms Protein Kinase Inhibitors Proto-Oncogene Proteins c-akt Treatment Outcome
A product of independent beta probabilities dose escalation design for dual-agent phase I trials.
adaptive design dose escalation dual-agent trial nonparametric phase I clinical trial Antineoplastic Combined Chemotherapy Protocols Clinical Trials Phase I as Topic Computer Simulation Dose-Response Relationship Drug Humans Logistic Models Maximum Tolerated Dose Research Design statistics Nonparametric
Practical implementation of the partial ordering continual reassessment method in a Phase I combination-schedule dose-finding trial.
Pavel Mozgunov, Thomas Jaki, Ioannis Gounaris, Thomas Goddemeier, Anja Victor, Marianna Grinberg
Nov 26, 2022