Professor Pamela Kearns MBChB, BSc (Hons), PhD, FRCPCH

Professor Pamela Kearns

Institute of Cancer and Genomic Sciences
Professor of Clinical Paediatric Oncology
Honorary Consultant in Paediatric Oncology

Contact details

Address
Cancer Research UK Clinical Trials Unit (CRCTU),
Institute of Cancer and Genomic Sciences,
University of Birmingham ,
Edgbaston,
Birmingham,
B15 2TT

Pamela Kearns is Professor of Clinical Paediatric Oncology in the Institute of Cancer and Genomic Sciences, University of Birmingham and an Honorary Consultant at the Birmingham Children’s Hospital. She is Director of the Cancer Research UK Clinical Trials Unit in the School of Cancer Sciences. She is President Elect for European Society of Paediatric Oncology (SIOP-E) and is on the Executive Board of the academic consortium 'Innovative Therapies for Children with Cancer' (ITCC).

She is currently a Senior Clinical Advisor for Cancer Research UK.

Her research is focused on the development of new therapies for refractory childhood leukaemias and lymphomas, extending from pre-clinical laboratory based studies through to early phase clinical trials.

Qualifications

  •  Fellowship of the Royal College of Paediatrics and Child Health 2009
  •  Certificate of Teaching and Learning in Higher Education, University of Newcastle 2000
  •  PhD (LLR Clinical Training Fellowship), University of Newcastle 2000
  •  Membership of the Royal College of Paediatrics and Child Health 1996
  •  Diploma in Medical Sciences, University of Newcastle
  •  Membership of the Royal College of Physicians (UK) Paediatrics 1993
  •  MBChB, Aberdeen University 1988
  •  BSc Honours. 2(1) Physiology, Aberdeen University 1982

Biography

Pamela Kearns was awarded a BSc Hons degree in Physiology at the University of Aberdeen and then went on to study Medicine in Aberdeen, graduating in 1988. She trained as a paediatric oncologist in Newcastle upon Tyne where, as a Leukaemia Research Fund (now Bloodwise) Clinical Fellow, she undertook her doctoral project investigating the role of glutathione and glutathione S transferases in chemoresistance in childhood acute lymphoblastic leukaemia. Two years of her doctoral research was spent working in the Paediatric Haemato-oncology Department of the Vrije University, Amsterdam under the supervision of Professor Rob Pieters.

After being awarded her PhD and completing her clinical training in paediatric oncology, she was appointed as a Clinical Senior Lecturer in Paediatric Oncology at the University of Bristol and Honorary Consultant Paediatric Oncologist at the Bristol Children’s Hospital.

In 2007, after 5 years in Bristol, she relocated to her current post at the University of Birmingham, to continue her translational research in resistant/refractory childhood acute leukaemias and lymphomas. Her laboratory-based research is focused on pre-clinical models for testing of novel treatments before they enter clinical trials. Her clinical research is focused on the design and development of early phase clinical trials investigating novel therapies for childhood leukaemias and lymphoma.

In 2010, she took on the role of Deputy Clinical Director within the Cancer Research UK Clinical Trials Unit, in the Institute of Cancer and Genomic Sciences, where she leads the national Children’s Cancer Trials Team. In 2012 she was appointed as Director of the Cancer Research UK Clinical Trials Unit. She promotes international collaborations in early phase clinical trials through her role on the Executive Committee of a European academic consortium call the ‘ITCC’ (Innovative Therapeutics for Children with Cancer) and as President elect of the European Society of Paediatric Oncology (SIOP-E).

Teaching

  • MBChB Year 5 Paediatric Course
  • MSc Clinical Oncology, Clinical trials, Paediatric Oncology and Translational Research in Cancer modules

Postgraduate supervision

Pamela is interested in supervising doctoral research students in translational research developing new therapeutic approaches for childhood lymphomas.

Doctoral research

PhD title The role of glutathione and glutathione S-transferases in childhood leukaemia

Research

Professor Kearns has been involved in several European research initiatives including the European Network for Cancer in Children and Adolescents ENCCA, which is an EU FP7 funded Network of Excellence the aim of which is to define and implement an integrated research strategy that will facilitate international investigator-driven clinical trials for childhood cancers. The work packages in which she is involved include development of a framework for clinical trials facilitation, delivering trial methodology for rare cancers and early drug development trials for childhood cancers.

Clinical Trials Research

Paediatric Oncology Drug Development Clinical Trials

Professor Kearns leads in national and international academic clinical trials evaluating new treatments for childhood malignancies.

Examples of trial for which she has been a lead investigator include:

• European Phase II study of clofarabine for refractory and relapsed childhood ALL: BIOV 111: European Chief Investigator; Pharma sponsored trial. Completed 2008. The results contributed to EMA marketing approval (2008) of clofarabine in this patient population.

• UK Phase I combination study of clofarabine and DaunoXome in childhood AML: CLOUD: Chief Investigator, Leukaemia and Lymphoma Research funded investigator led trial. The trial opened January 2009 and closed April 2011. Manuscript is in preparation.

• European Phase I study of aplidin for relapsed childhood solid tumours and leukaemias: UK co-Investigator, Pharma sponsored trial; completed 2008. Geoerger B, et al EJC 2012.

• European Phase I/II study for SRC family kinase inhibitor, dasatinib in childhood leukaemias. UK Lead Investigator; Pharma sponsored trial; completed 2009. Trial is part of EMA approved Paediatric Investigation Plan to wards marketing authorisation in the paediatric population.  Zwaan et al JCO 2013.

• International (Europe/US) Phase I and Phase II studies of nilotinib in childhood Philadelphia positive leukaemias. European Chief Investigator; Pharma sponsored trial. Trial part of the EMA approved Paediatric Investigation towards marketing authorisation in the paediatric population. Phase I June 2011- March 2015, phase II recruitment completed 2016. Manuscript in preparation

• European Phase I study of decitabine and cytarabine in childhood AML and lymphomas. European Chief Investigator; Pharma sponsored trial funded by Pharma. Trial open in Q1 2014.

Translational Research:

Professor Kearns' primary research interest is experimental therapeutics in childhood leukaemia focussed on refractory and relapsed leukaemia and lymphoma with the aim of developing innovative, targeted therapy based on the characterisation of the genetic/epigenetic and pharmacological basis of their disease resistance

She has  established  predictive pre-clinical in vitro and in vivo models to evaluate clinical efficacy of novel therapeutic approaches for acute leukaemias and lymphoma. Exploiting the engraftment capacity of human primary tumours in immuno-compromised mice, her group have established in vivo leukaemia models for ALL, AML and lymphomas and is investigating the therapeutic efficacy of novel agents with specific reference to target specificity and potential pharmacodynamic endpoints.

Other activities

National Committees

  • CR UK New Agents Committee (January 2013- to date)
  • National Cancer Research Institute (NCRI) Childhood Cancer and Leukaemia Clinical Study Group (April 2010 to date)
  • NCRI Childhood Cancer and Leukaemia New Agents Sub-Group (April 2010 to date)
  • Bone Cancer Research Trust BCRT Independent Scientific Advisory Panel (April 2013 to date. Chair from December 2016)

Previous committees

  • CCLG Biological Studies Steering Group (Member 2003-2009 and Chair 2005-2009)
  • Leukaemia and Lymphoma Research Cell Bank Steering Committee (2005 - 2012)
  • Leukaemia Research Fund Clinical Trials Advisory Panel (2003 - 2009)
  • Royal College of Paediatrics and Child Health (RCPCH) College Specialist Advisory Committee: academic representative (September 2009 to March 2015)
  • West Midlands Academic Health Sciences Network Clinical Trials Advisory Group (April 2014 to August 2016)

 International Committees

  • European Society of Paediatric Oncology (SIOP-E) Executive Board Member (From January 2013, President –Elect from January 2017)
  • Innovative Therapeutics in Childhood Cancer (ITCC) Executive Board: elected Board member and Treasurer (July 2010 to date)
  • ITCC European Sponsors Consortium Committee; Chair November 2014 to date
  • International-BFM Study Group Early Clinical Trials Committee (Founder Member and Co-chair 2006 to date)
  • Data Safety Monitoring Committee for Nordic Society of Paediatric Haematology and Oncology (NOPHO) randomised controlled trial for childhood acute lymphoblastic leukaemia (2009 to 2016; trial completed)

Publications

PEER REVIEWED PUBLICATIONS IN LAST 5 YEARS

Vormoor B, Veal GJ, Griffin MJ, Boddy AV, Irving J, Minto L, Case M, Banerji U3,4, Swales KE, Tall JR, Moore AS, Toguchi M5, Acton G, Dyer K, Schwab C, Harrison CJ, Grainger JD, Lancaster D, Kearns P, Hargrave D, Vormoor J.  A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia. Pediatr Blood Cancer. 2016 Dec 1 doi:10.1002/pbc.2635 [Epub ahead of print]

Main C, Stevens SP, Bailey S, Phillips R, Pizer B, Wheatley K, Kearns PR, English M, Wilne S, Wilson JS. The impact of routine surveillance screening with magnetic resonance imaging (MRI) to detect tumour recurrence in children with central nervous system (CNS) tumours: protocol for a systematic review and meta-analysis. Syst Rev. 2016 Aug 31;5(1):143. doi: 10.1186/s13643-016-0318-1

Main C, Dandapani M, Pritchard M, Dodds R, Stevens SP, Thorp N, Taylor RE, Wheatley K, Pizer B, Morrall M, Phillips R, English M, Kearns PR, Wilne S, Wilson JS. The effectiveness and safety of proton beam radiation therapy in children with malignant central nervous system (CNS) tumours: protocol for a systematic review. Syst Rev. 2016 Jul 27;5(1):124. doi: 10.1186/s13643-016-0285-6.

Pearson ADJP, Herold R, Rousseau R, Copland C, Bradley-Garelik B, Binner B, Capdeville R, Caron H, Carleer J, Chesler L, Geoerger  B, Kearns P, Marshall LV, Pfister SM, Schleiermacher G, Skolnik J, Spadoni C, Sterba J, van den Berg  H, Uttenreuther-Fischer M, Witt O, Norga K, Vassal G, on behalf of Members of Working Group 1 of the Paediatric Platform of ACCELERATE, Implementation of mechanism of action biology-driven early drug development for children with cancer. European Journal of Cancer 2016; 62  124- 131

Nailor A, Walker DA, Jacques TS, Warren KE, Brem H, Kearns PR, Greenwood J, Penny JI, Pilkington GJ, Carcaboso AM, Fleischhack G, Macarthur D, Slavc I, Meijer L, Gill S, Lowis S, van Vuurden DG, Pearl MS, Clifford SC, Morrissy S, Ivanov DP, Beccaria K, Gilbertson RJ, Straathof K, Green JJ, Smith S, Rahman R, Kilday JP. Highlights of Children with Cancer UK's Workshop on Drug Delivery in Paediatric Brain Tumour. Ecancermedicalscience. 2016 Mar 31;10:630.

Bautista F, Van der Lugt J, Kearns PR, Mussai FJ, Zwaan CM, Moreno L. The development of targeted new agents to improve the outcome for children with leukemia. Expert Opin Drug Discov. 2016 Nov;11(11):1111-1122.

Scholfield DW, Brundler MA, McDermott AL, Mussai F, Kearns P. Adjunctive Treatment in Juvenile Nasopharyngeal Angiofibroma: How Should We Approach Recurrence? J Pediatr Hematol Oncol. 2016 Apr;38(3):235-9.

Williams MT, Yousafzai YM, Elder A, Rehe K, Bomken S, Frishman-Levy L, Tavor S, Sinclair P, Dormon K, Masic D, Perry T, Weston VJ, Kearns P, Blair H, Russell L, Heidenreich O, Irving JA, Izraeli S, Vormoor J, Graham GJ, Halsey C. The ability to cross the blood-cerebrospinal fluid barrier is a generic property of acute lymphoblastic leukaemia blasts. Blood. 2016, Feb 11. pii: blood-2015-08-665034. [Epub ahead of print]

Main C, Wilson JS, Stevens SP, Houlton AE, English M, Kearns PR, Phillips B, Pizer B, Wilne S, Wheatley K. The role of high-dose myeloablative chemotherapy with haematopoietic stem cell transplantation (HSCT) in children with central nervous system (CNS) tumours: protocol for a systematic review and meta-analysis. Syst Rev. 2015 Nov 20;4(1):168.

Mussai F, Egan S, Higginbotham-Jones J, Perry T, Beggs A, Odintsova E, Loke J, Pratt G, U KP, Lo A, Ng M, Kearns P, Cheng P, De Santo C. Arginine dependence of Acute Myeloid Leukaemia blast proliferation: a novel therapeutic target. Blood 2015 Feb 20

Mussai FJ, Yap C, Mitchell C, Kearns P. Challenges of clinical trial design for targeted agents against pediatric leukemias. Front Oncol. 2015 Jan 6;4:374

Moroz V, Wilson JS, Kearns P, Wheatley K. Comparison of anticipated and actual control group outcome in randomised trials in paediatric oncology provides evidence that historically controlled studies are biased in favour of the novel treatment. Trials.2014, 15:481

Thomas A, Perry T, Berhane S, Oldreive C, Zlatanou A, Williams LR, Weston VJ, Stankovic T, Kearns P, Pors K, Grand RJ, Stewart GS. The dual acting chemotherapeutic agent Alchemix induces cell death independently of ATM and p53, Oncogene 2014 1-14

Vassal G, Fitzgerald E, Schrappe M, Arnold F, Kowalczyk J, Walker D, Hjorth L, Riccardi E,  Kienesberger A, Pritchard-Jones K, Valsecchi MG, Janic D, Hasle H, Kearns P, Petrarulo G, Florindi F, Essiaf S, Ladenstein R. Challenges for children and adolescents with cancer in Europe: the SIOP-Europe agenda. Paediatric Blood and Cancer 2014, Sep;61(9):1551-7

Leonard SM Perry T, Woodman C, Kearns P Sequential treatment with cytarabine and decitabine has an increased anti-leukemia effect compared to cytarabine alone in xenograft models of childhood acute myeloid leukaemia. 2014 PLoS One. 2014 Jan 28;9(1):e87475.

Kearns P, Morland B. New drug development in childhood cancer. Curr Opin Pediatr 2014, 26:37–42

Cader FZ, Vockerodt M, Bose S, Nagy E, Brundler MA, Kearns P, Murray PG. The EBV oncogene LMP1 protects lymphoma cells from cell death through the collagen-mediated activation of DDR1. Blood. 2013 Dec 19;122(26):4237-45

Batra R, Abbott J, Jenkinson H, Ainsworth JR, Cole T, Parulekar MV, Kearns P. Long-term retinoblastoma follow-up with or without general anaesthesia. Pediatr Blood Cancer. 2014 Feb;61(2):260-4

Bailey S, Howman A, Wherton D,  Pizer B, Fisher D , Kearns P , Picton S , Saran F , Wheatley K, Gibson M, Glaser A, Connolly D, Hargrave D. Diffuse Intrinsic Pontine Glioma treated with prolonged temozolomide and radiotherapy – results of a United Kingdom Phase II Trial (CNS 2007 04) Eur J Cancer. 2013 Dec;49(18):3856-62

Da Costa D, Agathanggelou A, Perry T, Weston V, Petermann E, Zlatanou A, Oldreive C, Wei W, Stewart G, Longman J, Smith E, Kearns P, Knapp S, Stankovic T.  BET inhibition as a single or combined therapeutic approach in primary paediatric B-precursor acute lymphoblastic leukaemia. Blood Cancer J. 2013 Jul 19;3:e126.

Kapatai G, Brundler MA, Jenkinson H, Kearns P, Parulekar M, Peet AC, McConville CM. Gene expression profiling identifies different sub-types of retinoblastoma. Br J Cancer. 2013 Jul 23;109(2):512-25.

Kearns P. The need for proportionate regulation of clinical trials. Lancet Oncol. 2013 May;14(6):454-5.

Zwaan CM, Rizzari C, Mechinaud F,  Lancaster DL,  Lehrnbecher T, van der Velden VHJ, Beverloo B,  den Boer ML, Pieters R, Reinhardt D, Dworzak M,  Rosenberg J, Manos G,  Agrawal S, Strauss L,  Baruchel A,  Kearns PR. Dasatinib in Children and Adolescents with Relapsed or Refractory Leukemia: Results of the CA180018 Phase I Dose-Escalation Study of the ‘Innovative Therapies for Children with Cancer’ Consortium.  J Clin Oncol. 2013 Jul 1;31(19):2460-8.

Irandoust M, Alvarez Zarate J, Hubeek I, van Beek EM, Schornagel K, Broekhuizen AJ, Akyuz M, van de Loosdrecht AA, Delwel R, Valk PJ, Sonneveld E, Kearns P, Creutzig U, Reinhardt D, de Bont ES, Coenen EA, van den Heuvel-Eibrink MM, Zwaan CM, Kaspers GJ, Cloos J, van den Berg TK. Engagement of SIRPα Inhibits Growth and Induces Programmed Cell Death in AML Cells. PLoS One. 2013;8(1):e52143.

Thompson CV, Wells JM, Bowen C, Brundler MA, Kearns P, Arul GS. Intra-abdominalkaposiform hemangioendothelioma and the benefits of laparoscopic surveillance. Pediatric Blood&Cancer 2012;58:992-3

GeoegerB, Estlin EJ, AertsI, Kearns P, Gibson B, Corradini N, Doz F, Lardelli P, Yovine  A, PradosR, Vassal G; on behalf of the European consortium Innovative Therapies for Children with Cancer (ITCC). A Phase I and Pharmacokinetic Study of Plitidepsin in Children with Advanced Solid Tumours: an Innovative Therapies for Children with Cancer (ITCC) study. European Journal of Cancer 2012 Feb;48(3):289-96

Expertise

New therapies for childhood leukaemias; early phase clinical trials; drug development for childhood cancers and leukaemia

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