Northern Institute for Cancer Research

Newcastle Cancer Centre Pharmacology Group

Newcastle Cancer Centre Pharmacology Group (NCCPG)

About

We work in close collaboration with the CRUK Centre for Drug Development, academic groups and pharma/biotech companies to conduct a wide range of clinical pharmacology studies across various phases of clinical trials.

Research Leader

Gareth Veal

The Newcastle Cancer Centre Pharmacology Group has well over 15 years of experience in conducting clinical pharmacology trials in both adult and paediatric oncology settings. Studies are carried out in early phase trials, providing essential pharmacokinetic outputs for the interpretation of clinical data, in addition to studies designed to optimise the dosing of currently used anticancer drugs in paediatric patient populations.

Early phase trials

An essential component of early phase (first in man) clinical trials is to determine the fate of a new drug when it is administered to patients. In order to be able to generate this clinical pharmacokinetic information, we develop and validate novel assays with the required level of sensitivity, precision and accuracy to quantify drug levels in blood samples collected from patients participating in early phase clinical trials. This allows us to determine how drugs are metabolised or broken down in the body and how quickly they are cleared from the circulation.

Childhood cancer studies

The NCCPG is the principal national centre for running clinical pharmacology studies in childhood cancer in the UK. Trials commonly involve pharmacokinetic, pharmacodynamic and pharmacogenetic aspects and are run either as stand-alone national pharmacology studies sponsored by the Newcastle upon Tyne Hospitals NHS Foundation Trust, or as part of larger national and European trials run through the Birmingham CRUK Clinical Trials Unit (CRCTU). Several studies have directly impacted on the treatment of children with cancer, in terms of personalisation of treatment based on therapeutic drug monitoring approaches. Similarly, results from recent trials have led to changes to dosing regimens and the development of new national treatment guidelines for specific drugs based on a pharmacological rationale. As part of our role in running national clinical pharmacology trials, we provide training to research nurses across the UK to ensure that studies are conducted to the same high standards at all clinical centres, helping to ensure the generation of high quality scientific data.

Staff members at a Research Nurse training day.

Facilities

All clinical trial work in our purpose-built clinical pharmacology laboratories within the Paul O’Gorman Building is carried out according to GCLP regulations. Our chromatography laboratory is well-equipped with High Performance Liquid Chromatography (HPLC), Liquid Chromatography-Mass Spectrometry (LC/MS) and Atomic Absorption Spectrometry (AAS) systems to allow the quantification of a range of anticancer drugs. Validated assays have been developed and validated for over 100 drugs and metabolites, including both well-established chemotherapeutics as well as drugs currently in early phase development.

Publications

White-Koning M, Osborne C, Paci A, Boddy AV, Chatelut E, Veal GJ. Investigating the potential impact of dose banding for systemic anti-cancer therapy in the paediatric setting based on pharmacokinetic evidence. European Journal of Cancer 2018, 91, 56-67.

Brock PR, Maibach R, Childs M, Rajput K, Roebuck D, Sullivan MJ, Laithier V, Ronghe M, Dall'Igna P, Hiyama E, Brichard B, Skeen J, Mateos ME, Capra M, Rangaswami AA, Ansari M, Rechnitzer C, Veal GJ, Covezzoli A, Brugières L, Perilongo G, Czauderna P, Morland B, Neuwelt EA. Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss. New England Journal of Medicine 2018, 378(25), 2376-2385.

Kim HY, Veal GJ, Zhou F, Boddy AV. The role of solute carrier (SLC) transporters in actinomycin D pharmacokinetics in paediatric cancer patients. European Journal of Clinical Pharmacology 2018 (In press).

Thomas F, Veal GJ, El Balkhi S, Lafont T, Picard N, Brugieres L, Chatelut E, Piguet C. Therapeutic drug monitoring and dose adaptation of cisplatin in a newborn with hepatoblastoma: a case report. Cancer Chemotherapy and Pharmacology 2018, 82(2), 361-365.

Duong JK, Veal GJ, Nath CE, Shaw PJ, Errington J, Ladenstein R, Boddy AV. Population pharmacokinetics of carboplatin, etoposide and melphalan in children: A re-evaluation of paediatric dosing formulas for carboplatin in patients with normal or mild impairment of renal function. Br J Clin Pharmacol 2018 (In press)

Zangarini M, Berry P, Sludden J, Raynaud FI, Banerji U, Jones P, Edwards D, Veal GJ. Development and validation of a LC-MS/MS method for the quantification of the checkpoint kinase 1 inhibitor SRA737 in human plasma. Bioanalysis 2017, 9(13), 1001-1010.

Zangarini M, Rajan N, Danilenko M, Berry P, Traversa S, Veal GJ. Development and validation of LC–MS/MS with in-source collision-induced dissociation for the quantification of pegcantratinib in human skin tumors. Bioanalysis 2017, 9(3), 279-288.

Veal GJ, Errington J, Sastry J, Chisholm J, Brock P, Morgenstern D, Pritchard-Jones K, Chowdhury T. Adaptive dosing of anticancer drugs in neonates – facilitating evidence-based dosing regimens. Cancer Chemotherapy and Pharmacology 2016, 77(4), 685-692.

Veal GJ, Cole M, Chinnaswamy G, Sludden J, Jamieson D, Errington J, Malik G, Hill CR, Chamberlain T, Boddy AV. Cyclophosphamide pharmacokinetics and pharmacogenetics in children with B-cell non-Hodgkin’s lymphoma. Eur J Cancer 2016 55: 56-64.

Jackson RK, Irving JAE, Veal GJ. Personalisation of dexamethasone therapy in childhood acute lymphoblastic leukaemia. Br J Haem 2016 173: 13-24.

Walsh C, Bonner JJ, Johnson TN, Neuhoff S, Ghazaly EA, Gribben JG, Boddy AV, Veal GJ. Development of a physiologically based pharmacokinetic model of actinomycin D in children with cancer. Br J Clin Pharmacol 2016 81: 989-998.

Errington J, Malik G, Evans J, Baston J, Parry A, Price L, Johnstone H, Peters S, Oram V, Howe K, Whiteley E, Tunnacliffe J, Veal GJ. Investigating the experiences of childhood cancer patients and parents participating in optional non-therapeutic clinical research studies in the UK – a qualitative study. Ped Blood Cancer 2016 63: 1193-1197.

Veal GJ, Errington J, Sastry J, Chisholm J, Brock P, Morgenstern D, Pritchard-Jones K, Chowdhury T. Adaptive dosing of anticancer drugs in neonates – facilitating evidence-based dosing regimens. Cancer Chemother Pharmacol 2016 77: 685-692.

Moreno L, Marshall LV, Pearson AD, Morland B, Elliott M, Campbell-Hewson Q, Makin G, Halford SE, Acton G, Ross P, Kazmi-Stokes S, Lock V, Rodriguez A, Lyons  JF, Boddy AV, Griffin MJ, Yule M, Hargrave D. A phase I trial of AT9283 (a selective inhibitor of aurora kinases) in children and adolescents with solid tumors: a Cancer Research UK study. Clin Cancer Res 2015 21: 267-273.

Veal GJ, Errington J, Hayden J, Hobin D, Murphy D, Dommett RM, Tweddle DA, Jenkinson H, Picton S. Carboplatin therapeutic monitoring in preterm and full-term neonates. Eur J Cancer 2015 51: 2022-2030.

Hill CR, Cole M, Errington J, Malik G, Boddy AV, Veal GJ. Characterisation of the clinical pharmacokinetics of actinomycin D and the influence of ABCB1 pharmacogenetic variation on actinomycin D disposition in children with cancer. Clin Pharmacokinet 2014 53: 741-751.
  
Veal GJ, Errington J, Rowbotham SE, Illingworth NA, Malik G, Cole M, Daly AK, Pearson ADJ, Boddy AV. Adaptive dosing approaches to the individualization of 13-cis-retinoic acid (isotretinoin) treatment for children with high-risk neuroblastoma. Clin Cancer Res 2013 19: 469-479.

Veal GJ, Nguyen L, Paci A, Riggi M, Amiel M, Valteau-Couanet D, Brock P, Ladenstein R, Vassal G. Busulfan pharmacokinetics following intravenous and oral dosing regimens in children receiving high-dose myeloablative chemotherapy for high-risk neuroblastoma as part of the HR-NBL-1/SIOPEN trial. Eur J Cancer 2012 48: 3063-3072.

Jarvis IWH, Meczes EL, Thomas HD, Edmonson RJ, Veal GJ, Boddy AV, Ottley CJ, Pearson DG, Tilby MJ.  Therapy-induced carboplatin-DNA adduct levels in human ovarian tumours in relation to assessment of adduct measurement in mouse tissues. Biochem Pharmacol 2012 83:69-77.

Chinnaswamy G, Errington J, Foot A, Boddy AV, Veal GJ, Cole M. Pharmacokinetics of cyclophosphamide and its metabolites in paediatric patients receiving high-dose myeloablative therapy. Eur J Cancer 2011 47: 1556-1563.

Israels T, Damen CWN, Cole M, van Geloven N, Boddy AV, Caron HN, Beijnen JH, Molyneux EM and Veal GJ. Malnourished Malawian patients presenting with large Wilms tumours have a decreased vincristine clearance rate. Eur J Cancer 2010 46: 1841-1847.

Projects

Find out more about the projects we've worked on.

Therapeutic Drug Monitoring for the Treatment of Childhood Cancer Patients

 

More projects coming soon...