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A phospho-proteomic study of cetuximab resistance in KRAS/NRAS/BRAFV600 wild-type colorectal cancer.
(SPRINGER, 2021-08-30)
PURPOSE: We hypothesised that plasticity in signal transduction may be a mechanism of drug resistance and tested this hypothesis in the setting of cetuximab resistance in patients with KRAS/NRAS/BRAFV600 wild-type colorectal ...
A Phase I Dose-escalation Study of AZD3965, an Oral Monocarboxylate Transporter 1 Inhibitor, in Patients with Advanced Cancer.
(AMER ASSOC CANCER RESEARCH, 2023-04-14)
PURPOSE: Inhibition of monocarboxylate transporter (MCT) 1-mediated lactate transport may have cytostatic and/or cytotoxic effects on tumor cells. We report results from the dose-escalation part of a first-in-human trial ...
Study protocol for a randomised controlled trial of enhanced informed consent compared to standard informed consent to improve patient understanding of early phase oncology clinical trials (CONSENT).
(BMJ PUBLISHING GROUP, 2021-09-06)
INTRODUCTION: Early phase cancer clinical trials have become increasingly complicated in terms of patient selection and trial procedures-this is reflected in the increasing length of participant information sheets (PIS). ...
A Phase I Trial of CT900, a Novel α-Folate Receptor-Mediated Thymidylate Synthase Inhibitor, in Patients with Solid Tumors with Expansion Cohorts in Patients with High-Grade Serous Ovarian Cancer.
(AMER ASSOC CANCER RESEARCH, 2022-11-01)
PURPOSE: CT900 is a novel small molecule thymidylate synthase inhibitor that binds to α-folate receptor (α-FR) and thus is selectively taken up by α-FR-overexpressing tumors. PATIENTS AND METHODS: A 3+3 dose escalation ...
Clinical trial designs for evaluating and exploiting cancer evolution.
(ELSEVIER SCI LTD, 2023-07-01)
The evolution of drug-resistant cell subpopulations causes cancer treatment failure. Current preclinical evidence shows that it is possible to model herding of clonal evolution and collateral sensitivity where an initial ...
A Phase I/II Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Low-Dose Gemcitabine in Patients with Advanced Cancer.
(AMER ASSOC CANCER RESEARCH, 2023-01-17)
PURPOSE: This was a Phase I/II trial of the novel checkpoint kinase 1 (Chk1) inhibitor SRA737 given in combination with gemcitabine. Its objectives were to establish the safety profile, recommended Phase 2 dose (RP2D), ...
Phase I Trial of the Human Double Minute 2 Inhibitor MK-8242 in Patients With Advanced Solid Tumors.
(AMER SOC CLINICAL ONCOLOGY, 2017-04-20)
Purpose To evaluate MK-8242 in patients with wild-type TP53 advanced solid tumors. Patients and Methods MK-8242 was administered orally twice a day on days 1 to 7 in 21-day cycles. The recommended phase II dose (RP2D) was ...
Critical parameters in targeted drug development: the pharmacological audit trail.
(W B SAUNDERS CO-ELSEVIER INC, 2016-08-01)
The Pharmacological Audit Trail (PhAT) comprises a set of critical questions that need to be asked during discovery and development of an anticancer drug. Key aspects include: (1) defining a patient population; (2) ...
A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours.
(ELSEVIER SCI LTD, 2016-11-01)
PURPOSE: We performed a multi-centre phase I study to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the orally available small molecule mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, ...
Clinical outcomes and prognostic factors of patients with advanced mesothelioma treated in a phase I clinical trials unit.
(ELSEVIER SCI LTD, 2017-04-01)
BACKGROUND: We have previously reported a prognostic score for patients in phase I trials in the Drug Development Unit, treated at the Royal Marsden Hospital (RPS). The RPS is an objective tool used in patient selection ...