A5001488061- Lung Cancer Treatments and Mutations
- Colorectal Cancer Treatments and Studies
- Cancer Treatment and Pharmacology
- Lipoproteins and Cardiovascular Health
- Lung Cancer Research Studies
- HER2/EGFR in Cancer Research
- Cancer Genomics and Diagnostics
- Health Systems, Economic Evaluations, Quality of Life
- Advanced Breast Cancer Therapies
- PARP inhibition in cancer therapy
- Sepsis Diagnosis and Treatment
- COVID-19 Clinical Research Studies
- Pharmaceutical Economics and Policy
- Cancer Immunotherapy and Biomarkers
- Ovarian cancer diagnosis and treatment
- Antiplatelet Therapy and Cardiovascular Diseases
- Immunotherapy and Immune Responses
- BRCA gene mutations in cancer
- Advanced Causal Inference Techniques
- Retinal and Optic Conditions
- Retinal Diseases and Treatments
- Statistical Methods in Clinical Trials
- Ocular Oncology and Treatments
- Long-Term Effects of COVID-19
- Retinal Imaging and Analysis
University of Louisville
2017
Lurie Children's Hospital
2016
AstraZeneca (United Kingdom)
2004-2014
Newcastle University
2013
AstraZeneca (Singapore)
2006-2012
AstraZeneca (Brazil)
2006-2010
University of New Mexico
2010
The University of Texas MD Anderson Cancer Center
2010
UNM Comprehensive Cancer Center
2010
Princess Margaret Cancer Centre
2009
Previous, uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients non–small-cell lung cancer.
Olaparib (AZD2281) is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor that has shown antitumor activity in patients with high-grade serous ovarian cancer or without BRCA1 BRCA2 germline mutations.We conducted a randomized, double-blind, placebo-controlled, phase 2 study to evaluate maintenance treatment olaparib platinum-sensitive, relapsed, who had received two more platinum-based regimens and partial complete response their most recent regimen. Patients were randomly...
The phase III Iressa Survival Evaluation in Lung Cancer (ISEL) trial compared gefitinib with placebo 1,692 patients refractory advanced non-small-cell lung cancer. We analyzed ISEL tumor biopsy samples to examine relationships between biomarkers and clinical outcome after treatment a placebo-controlled setting.Biomarkers included epidermal growth factor receptor (EGFR) gene copy number by fluorescence situ hybridization (n = 370); EGFR 379) phosphorylated Akt (p-Akt) protein expression 382)...
Rationale: Interstitial lung disease (ILD) occurs in Japanese patients with non–small cell cancer (NSCLC) receiving gefitinib.Objectives: To elucidate risk factors for ILD NSCLC during treatment gefitinib or chemotherapy.Methods: In a prospective epidemiologic cohort, 3,166 advanced/recurrent were followed 12 weeks on 250 mg (n = 1,872 periods) chemotherapy 2,551). Patients who developed acute 122) and randomly selected control subjects 574) entered case-control study. Adjusted incidence...
Abstract Introduction This Phase I study evaluated the safety, tolerability and efficacy of olaparib, a potent oral poly(ADP-ribose) polymerase (PARP) inhibitor, in combination with paclitaxel patients metastatic triple-negative breast cancer (mTNBC). Methods Eligible who had received ≤1 prior cytotoxic regimen for mTNBC were treated olaparib 200 mg bid continuously plus weekly 90 mg/m 2 three weeks per four-week cycle. Dose modifications large proportion due to neutropenia resulted...
Abstract Purpose: This phase II randomized trial evaluated the efficacy and tolerability of anastrozole combined with gefitinib or placebo in women hormone receptor–positive metastatic breast cancer (MBC). Experimental Design: Postmenopausal measurable evaluable MBC who had not received prior endocrine therapy for this disease stage developed during/after adjuvant tamoxifen were eligible. The primary response variable was progression-free survival (PFS) secondary variables included clinical...
8009^ Background: AZD9291 is a selective, third generation EGFR-TKI, effective against both EGFR-TKI sensitizing and resistance T790M mutations in preclinical models. We are conducting phase I study of EGFR mutant (EGFRm+) NSCLC pts. Methods: EGFRm+ pts, with acquired to EGFR-TKIs, were enrolled multicenter trial (NCT01802632) into dose escalation expansion cohorts. was administered orally, at doses 20–240 mg once daily. Stable brain metastases allowed. All pts assessed for pharmacokinetics...
Abstract Introduction/Aims Trials incorporating placebo‐to‐active treatment crossover are encouraged in fatal conditions like amyotrophic lateral sclerosis (ALS) but may underestimate active survival benefit. Here, we apply methods for modeling without crossover, including the rank‐preserving structural failure time model (RPSFTM), to data from CENTAUR trial of sodium phenylbutyrate and taurursodiol (PB TURSO) ALS both randomized placebo‐controlled open‐label extension (OLE) phases. Methods...
In parallel group trials, long‐term efficacy endpoints may be affected if some patients switch or cross over to the alternative treatment arm prior event. oncology experimental can occur in control following disease progression and potentially impact overall survival. It a clinically relevant question estimate that would have been observed no had switched, for example, ‘real‐life’ clinical effectiveness health technology assessment. Several commonly used statistical methods are available try...
Tebentafusp demonstrated a superior overall survival (OS) benefit [hazard ratio (HR) 0.51] compared to investigator's choice (82% pembrolizumab) in randomized, phase III trial (IMCgp100-202; N = 378) untreated metastatic uveal melanoma (mUM). The 1-year OS rates for tebentafusp and pembrolizumab were 73% 59%, respectively. In the single-arm GEM1402 (N 52), rate nivolumab plus ipilimumab (N+I) mUM was 52%. Due limitations conducting randomized trials mUM, we on or (IMCgp100-202) N+I (GEM1402)...
The ISEL (Iressa Survival Evaluation in Lung Cancer) clinical trial evaluated the efficacy of gefitinib versus placebo pretreated nonsmall-cell lung cancer patients. Two different antibodies, scoring systems, and cutoff points epidermal growth factor receptor (EGFR) protein expression were compared to predict response survival enrolled patients.EGFR was assessed tumor samples by immunohistochemistry using Dako EGFR pharmDx kit (scoring percent cells with positive staining) Zymed monoclonal...
5003 Background: Olaparib (AZD2281) is an oral PARP inhibitor that has shown antitumor activity in patients (pts) with high-grade serous ovarian cancer (SOC) and without BRCA1 or BRCA2 mutations. This randomized, double-blind, multicenter, placebo-controlled Phase II study evaluated maintenance treatment olaparib pts PSR SOC (clinicaltrials.gov; NCT00753545). Methods: Pts who had received ≥2 previous platinum regimens were a maintained partial complete response following their last...
This paper illustrates an approach to setting the decision framework for a study in early clinical drug development. It shows how criteria go and stop are calculated based on pre‐specified target lower reference values. The can lead three‐outcome by including consider zone; this could enable smaller studies be performed development, with other information either external or within used reach decision. In way, Phase I/II trials geared towards providing actionable decision‐making rather than...
1012 Background: Preclinical data provide evidence that suggests crosstalk between growth factor receptor pathways and the estrogen (ER). Inhibition of both epidermal ER signalling may thus be a potential intervention to overcome hormonal resistance. We performed phase II study evaluate efficacy tolerability anastrozole (Arimidex) plus gefitinib (IRESSA) [A+G] vs. placebo [A+P] for treatment newly diagnosed HR+ MBC in postmenopausal women. Methods: A total 94 women with were randomized (1:1)...
8001 Background: In INTEREST, gefitinib demonstrated non-inferior overall survival (OS), more favorable tolerability and improved QoL vs docetaxel in advanced pretreated NSCLC. We examined potential clinical biomarker correlations with efficacy. Methods: Pre-defined subgroups included histology, performance status, prior platinum paclitaxel therapy, number of regimens, smoking history, gender, ethnicity. Tumor tissues were evaluated by FISH, IHC, direct-gene sequencing PCR for EGFR gene-copy...
In studies with time‐to‐event data, outcomes may be reported as hazard ratios (HR) or binomial counts/proportions at a specific time point. If the intent is to synthesise evidence by performing meta‐analysis network (NMA) using HR measure of treatment effect, that only report data cannot included in network. Methods for converting HRs were investigated, so reporting could data. Estimating log relatively straightforward under assumptions proportional hazards and minimal censoring standard...
Measures taken to address climate change and sustainability, more generally, imply a major reconfiguration of infrastructure systems the built environment. Action across so many functions necessarily involves range organisations that may have differing priorities motivations. This paper presents concept decision theatre describes how this approach was tested by co-designing, with stakeholders, two events identify current vulnerabilities city Newcastle upon Tyne storm event investigate...
Suppressing perioperative inflammation and post-operative atrial fibrillation requires effective drug delivery platforms (DDP). Localized anti-inflammatory anti-arrhythmic agent release may be more than intravenous treatment to improve patient outcomes. This study utilized a dexamethasone (DEX) amiodarone (AMIO)-loaded Parylene-C (PPX) nano-structured film inhibit fibrillation. The PPX was tested in an established pericardial adhesion rabbit model. Following sternotomy, the anterior...