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Glioma Research Group

Group Leader: Dr Paul Mulholland

Clinical trials
Selected publications

Introduction

Our goal is to improve clinical outcomes for patients with glioma, from pre-clinical development of novel therapies to early and later phase clinical trials. The clinical practice is based at University College London Hospitals and the National Hospital for Neurology & Neurosurgery. Our main research interests are understanding the immune microenvironment of glioblastoma and utilising this to improve the efficacy of immunotherapeutic agents in clinical practice. We are also researching targeted hyperthermia (www.DARTRIX.eu) as a treatment modality for relapsed glioblastoma with Prof Kerry Chester.


Clinical trials

In set-up: 

  • Intellance 1 (NCT02573324) A Study of ABT-414 in Subjects With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification 
  • Checkmate548 (NCT02667587) Study of Temozolomide Plus Radiation Therapy With Nivolumab or Placebo, for Newly Diagnosed Patients With Glioblastoma 
  • CheckMate 498 (NCT02617589) Study of Nivolumab Versus Temozolomide, Given With Radiation Therapy, for Newly-diagnosed Patients With Glioblastoma

Previous trials: 

  • REGAL A phase III, randomised, multi-centre study in subjects with recurrent glioblastoma multiforme to compare the efficacy of cediranib monotherapy and the combination of cediranib with lomustine to the efficacy of lomustine alone. 
  • CENTRIC A phase III, randomised, multi-centre study in subjects with newly diagnosed glioblastoma multiforme and methylated MGMT gene promoter to compare the efficacy of cilengitide in combination with standard treatment versus standard treatment alone. 
  • SAPPHIRE A phase III, randomised, multi-centre study in subjects with recurrent or refractory anaplastic astrocytoma (WHO grade III) to compare the efficacy and safety of AP 12009 to standard treatment with temozolomide or BCNU.
  • L19SIP A phase II, non-randomised, multi-centre study of 131I-L19SIP radioimmunotherapy in combination with whole brain radiotherapy in patients with multiple brain metastases from solid tumours. 
  • DORIC A phase II, randomised, multicentre study in subjects with recurrent glioblastoma to compare the efficacy of cediranib plus placebo and the combination of cediranib and gefitinib (Iressa). 
  • EORTC 26082 -22081 A phase II radiation therapy and concurrent plus adjuvant Temsirolimus (CCI-779) versus chemo-irradiation with TMZ in newly diagnosed GBM without methylation of the MGMT gene promoter. 
  • IMA950 A Cancer Research UK Phase I trial of IMA950 (a novel multi-peptide vaccine) plus GM-CSF in patients with newly diagnosed glioblastoma. 
  • TAMIGA A double-blind, placebo-controlled, randomized, Phase IIIb trial evaluating the efficacy and safety of standard of care (SOC) +/-continuous bevacizumab treatment following progression of disease (PD) in patients with glioblastoma (GBM) after first (1st)-line treatment with radiotherapy, temozolomide and bevacizumab. 
  • TAVAREC Randomised phase II trial assessing the significance of Bevacizumab in recurrent grade II and grade III gliomas.
  • CHECKMATE 143 A Randomized Phase IIB Open Label Study of Nivolumab versus Bevacizumab in Adult Subjects with Recurrent Glioblastoma 
  • FAK113517 Phase I study of a Focal Adhesion Kinase Inhibitor in Subjects With Solid Tumors 

Selected publications

Chiara Bardella, Osama Al-Dalahmah, Daniel Krell, Pijus Brazauskas, Khalid Al-Qahtani, Marketa Tomkova, Julie Adam, Sebastian Serres, Helen Lockstone, Inga Pfeffer, Nicola Sibson, Robert Goldin, Benjamin Schuster-Böeckler, Patrick Pollard, Tomoshi Soga, James McCullagh, Christopher Schofield, Paul Mulholland, Olaf Ansorge, Skirmantas Kriaucionis, Peter Ratcliffe, Francis G. Szele and Ian Tomlinson. Expression of the Idh1R132H driver mutation in the murine subventricular zone stem cell niche recapitulates early gliomagenesis. Cancer Cell. In Press, 2016

Thomas Carter, Paul Mulholland, Kerry Chester. Antibody-Targeted Nanoparticles for Cancer Treatment. Future Medicine. In Press, 2016.

N F Brown, D Krell and P Mulholland. Chemotherapy for Brain Tumours. Book Chapter. Oxford Textbook of Neurosurgery. In Press, 2016.

Roy Rampling, Sharon Peoples, Paul J. Mulholland, Allan James, Omar Al-Salihi, Christopher J. Twelves, Catherine McBain, Sarah Jefferies, Alan Jackson, Willie Stewart, Juha Lindner, Sarah Kutscher, Norbert Hilf, Lesley McGuigan, Jane Peters, Karen Hill, Oliver Schoor, Harpreet Singh-Jasuja, Sarah E. Halford, James W.A. Ritchie. A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multi-Peptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma. Clin Cancer Res. 2016 May 25. pii: clincanres.0506.2016. 

Nicholas Brown, Catherine McBain, Stephen Nash, Kirsten I Hopkins, Paul Sanghera, Frank Saran, Mark Phillips, Fiona Dungey, Laura Clifton-Hadley, Katharina Wanek, Daniel Krell, Sarah Jeffries, Iftekhar Khan, Paul Smith, Paul Mulholland. Multi-center randomized phase II study comparing cediranib plus gefitinib with cediranib plus placebo in subjects with recurrent/progressive glioblastoma. PLoS One. 2016 May 27;11(5):e0156369. doi: 10.1371/journal.pone.0156369.

Thomas Carter, Heather Shaw, Denise Cohn-Brown, Kerry Chester, Paul Mulholland. Ipilimumab and bevacizumab in glioblastoma. Clin Oncol (R Coll Radiol). 2016 May 8. pii: S0936-6555(16)30076-0. doi: 10.1016/j.clon.2016.04.042. [Epub ahead of print]

Krell D, Mulholland P, Stebbing J, Tomlinson, Bardella C. Hot mutation screening in human glioblastoma. Future Science Open. 2015June doi:10.4155.

Maha R.A. Abdollah, Tammy Kalber, Berend Tolner, Paul Southern, Joseph C. Beard, Mathew Robson, R. Barbara Pedley, Ivan P. Parkin, Quentin Pankhurst, Paul Mulholland and Kerry Chester. Prolonging the Circulatory Time of NIR-Dye Labelled SPION Using Dextran Sulfate. Faraday Discuss. 2014; 175:41-58.

Tracy Batchelor, Paul Mulholland, Bart Neyns, et al. Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol. 2013 Sep 10;31(26):3212-3218. 

Maclean J, Fersht N, Singhera M, Mulholland P et al. Multi-disciplinary management for patients with oligometastases to the brain: results of a 5 year cohort study. Radiat Oncol. 2013 Jun 27;8:156.

Daniel Krell, Paul Mulholland, Adam E. et al. Isocitrate Dehydrogenase mutations in tumourigenesis and their potential role as novel therapeutic targets. Future Oncology 2013 Dec;9(12):1923-35.

D Ulahannan, M B Kovac, P J Mulholland, J-B Cazier and I Tomlinson. Technical and implementation issues in using next-generation sequencing of cancers in clinical practice. Br J Cancer. 2013 Aug 20;109(4):827-35. 

Tim Forshew, Paul Lewis, Adam Waldman, David Peterson, Mark Glaser, Cathryn Brock, Denise Sheer and Paul J. Mulholland. Three Different Brain Tumours Evolving from a Common Origin. Oncogenesis. 2013 Apr 1;2:e41. 

Daniel Krell, Mauelikem Assoku, Malcolm Galloway, Paul Mulholland, Ian Tomlinson, Chiara Bardella. Screen for IDH1, IDH2, IDH3, D-2HGDH and L-2HGDH mutations in glioblastoma. PLoS One. 6 (5): e19868, 2011.

Paul J. Mulholland, Heike Fiegler, Patricia Gorman, Peter Sasieni, Joanna Adams, Koichi Ichimura, Jane W. Babbage, Tania A. Jones, Radost Vatcheva, Philip East, Philippa Carr, Chrysanthos Poullikas, V. Peter Collins, Nigel P. Carter, Ian P.M. Tomlinson & Denise Sheer. Genomic profiling identifies discrete deletions associated with translocations in glioblastoma multiforme. Cell cycle. 5(7): 783-791, 2006.

Mulholland PJ, Thirlwell C, Brock CS and Newlands ES. Emerging targeted treatments for astrocytic glioma. Expert opinion on emerging drugs. 10: 845-854, 2005. 

Paul J. Mulholland. Update on temozolomide in the management of glioblastoma multiforme. MIMS Adv. Neurooncology. 1(2): 14-15, 2005.

Paul J. Mulholland and Edward S. Newlands. Overview of the current medical management of primary brain tumours. MIMS Adv. Neurooncology.  1(1): 2-5, 2004.

Mulholland PJ, Ferry DR, Anderson D, Hussain SA, Young AM, Cook JE, Hodgkin E, Seymore LW and Kerr DJ. Pre-clinical and clinical study of QC12, a water-soluble, pro-drug of quercetin. Ann Oncol. 12(2): 245-8, 2001.