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Brain Tumor CSG 2007-8 Annual Report

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Brain Tumor CSG 2007-8 Annual Report Brain Tumor CSG 2007-8 Annual Report Document Transcript

  • Annual report 2007-8NCRI Brain Tumour Clinical Studies GroupIntroductionThe Brain Tumour Clinical Studies Group (BTSG) has continued to work towardsincreasing the range of clinical studies available for brain tumour patients in the UK. Inthe past year we have also begun to address some of the long term issues underlyingpoor recruitment in rare tumour types, identified new funding sources to help supportbrain tumour studies and forged closer links with the paediatric and teenage and youngadult groups. The newly set up expertise based subgroups of the BTSG have all beenvery active in the last year and several new study ideas are being developed throughthem.Membership and structureSince the progress review in February 2007, five expertise based subgroups have beenset up to address research issues in imaging, translational research, palliative care,technology development and use of new agents in brain tumours. These have been veryactive in the last year and several new study ideas have been brought forward. Mostnotably the Novel Agents Subgroup has been involved in the design of 2 new phase Istudies in GBM and CNS lymphoma respectively and a phase II study using a novelrepair inhibitor with radiation in poor prognosis GBM. The Palliative Care Subgroup hasalso begun a pilot study addressing the needs of carers of brain tumour patients. TheImaging Subgroup has been very active in exploring means of co-ordinating theapproach to use of novel imaging in clinical studies and are preparing a major review ofthis subject. The Surgical Technology Subgroup is focusing on designing a study toassess the utility of convection enhanced delivery of cytotoxic agents.Portfolio and accrualThere are 3 trials currently open in the Group’s portfolio; all are in set up (see Table Ibelow). 2 further trials are open in collaboration with the Radiotherapy and Lung CSG’s,OSCAR and TACTIC respectively. New trials under discussion include a tumourgenetics study and several phase II studies testing the effect of novel agents (seebelow).In the past year the group has successfully completed recruitment to the BR12 trial,which compared the efficacy of Temozolomide against PCV (Procarbazine, CCNU,Vincristine) chemotherapy in chemonaïve patients with recurrent malignant glioma. Thetranslational study linked to the BR12 trial is ongoing and preliminary data have beenpresented. The first clinical data will be available later in 2008.The Group has also collaborated with the EORTC on a randomised trial examining therole of whole brain radiotherapy after resection or radiosurgery for patients with 1-3 brainmetastases. Although recruitment began slowly, increased participation from newcentres enabled more rapid recruitment during 2006 and 2007 and the trial was closed inOctober 2007.A further phase III EORTC study addressing the effect of dose dense temozolomidecompared to standard dose temozolomide in newly diagnosed glioblastoma multiformepatients is open in selected centres and is recruiting extremely rapidly, with several UKcentres contributing large patient numbers. The Group has joined the EORTC in thedevelopment and implementation of a low-grade glioma trial, which comparesTemozolomide versus radiotherapy in patients with progressive grade II astrocytomas, -1-
  • Annual report 2007-8oligodendrogliomas and mixed tumours (EORTC 22033 – 26033), which will openshortly.The major trial in set up is the CATNON (BR14/TATA trial), to examine the role ofchemotherapy in patients with grade III astrocytoma (non1p,19q deleted anaplasticglioma). This study will be a major collaborative study between MRC/EORTC and RTOGwith a substantial translational component.Table 1: Brain Tumour CSG PortfolioAcronym Title PI(s) Status Adjuvant procarbazine, CCNU and vincristine chemotherapy in patients withBR11 Closed highly anaplastic oligodendroglioma (in collaboration with the EORTC). Temozolomide vs PCV chemotherapy in the Prof Michael ClosedBR12 treatment of recurrent malignant glioma Brada A randomised controlled trial of temozolomide as adjuvant and/orBR14 in Set-up concurrent treatment in anaplastic (WHO grade III) gliomaEORTC Primary chemotherapy with temozolomide22033-26033 - vs. radiotherapy in patients with low gradeLow grade Dr Jeremy Rees in Set-up gliomas with stratification for genetic 1pglioma trial loss: a phase III study(BR13) No Radiotherapy versus Whole Brain Radiotherapy for 1 to 3 Brain MetastasesEORTC 22952 from Solid Tumor after Surgical Resection Dr R Soffietti Closed or Radiosurgery. A Randomized Phase III Trial. Phase III Trial comparing Conventional Adjuvant Temozolomide with DoseEORTC 26052 Dr Sara Erridge in Set-up Intensive Temozolomide in Patients with Newly Diagnosed GlioblastomaNeo-adjuvant Multicentre, Phase II Study of CarboplatinCarboplatin pre-irradiation in patients with primary ClosedTrial glioblastoma multiforme following biospyThe current activity of each subgroup is shown below in Table 2.164 patients were recruited to Brain studies in 2007-8 representing 3.9% of incidencecases. All were to RCTs. Publications for the reporting year can be found in Appendix 1.Table 2: Subgroup activity -2-
  • Annual report 2007-8Sub-group Current priorities Studies under discussionPalliative care QOL in brain tumour carers Questionnaire study of carers of glioma patients Interventions for treatment related fatigue Complementary therapy intervention for RT related fatigueTranslational research BR12 translational study Ongoing Novel agents in In vitro studies with anti- meningioma tubulin agent ongoing New approaches to Phase II study of anti- Schwannoma angiogenic agentImaging Defining role of new Bolt-on imaging study to imaging techniques as EORTC 26052 biomarkers in clinical studies Co-ordinating assessment of image data across research active centresNew agents Use of DNA repair inhibitors Phase II study of RT + Parp as radiosenitisers inhibitor for elderly/poor performance status GBM Anti-angiogenic agents with patients standard treatment of HGG Use of MRI biomarkers Phase I study of HD Methotrexate with Phase 0 trials to investigate Glucarpidase in CNS PD and biomarker lymphoma endpointsTrials in developmentThe trials in development are summarized in Table 3 below.Table 3: Studies under developmentStudy PI Design/statusRadiotherapy with Adjuvant Roger Taylor Single arm phase IIChemotherapy for Adults with Submitted to CTAACIntracranial Primitive Neuro-ectodermal Tumour (PNET)(CAPNET)PARP inhibitors with radiotherapy in Anthony Phase II -3-
  • Annual report 2007-8poor prognosis GBM Chalmers Under development in new agents groupRadiosurgery and Laptinib in HER2+ Lucy Brazil Randomised phase IIbreast cancer brain metastases Under discussion with GSKQuality of life issues in carers of brain Angela Pilot questionnaire studytumour patients Costello Palliative Care SubgroupMeetingsA major focus in the last year has also been addressing poor access to studies in youngadults with brain tumours and forging closer links with the paediatric oncology groups. Asuccessful one-day meeting was held in December 2007 including a series of talks anddiscussion to begin to plan a future joint agenda. A further more focussed meeting isplanned for 2008 and an opinion document will be published on behalf of thosecontributing to the first meeting.CollaborationsThe Group is collaborating in two national brain metastases trials. The OSCAR trial,developed with the Radiotherapy CSG, is assessing the role of radiotherapy in poorprognosis patients with multiple brain metastases from non-small cell lung cancer andwill randomise patients between best supportive care and whole brain irradiation. TheTACTIC trial, developed in collaboration with the Lung CSG, is assessing the value ofErlotinib (Tarceva) in addition to whole brain radiotherapy using a randomised phase IItrial design in patients with inoperable brain metastases from non-small cell lung cancer.Both trials are now open. Further studies for patients with brain metastases from HER2+breast cancer and melanoma are under discussion with the relevant NCRI Clinical StudyGroups.Other activitiesThe Group has been aware of the problems inherent in clinical research in rare tumourtypes in accessing local resources to support study entry including data management,research nurse and research administration support. Following discussions at CSGmeetings an initiative has been agreed with CRUK and The Samantha Dixon BrainTumour Trust (SDBTT) to make targeted funding available for clinical research in tobrain tumours through the Comprehensive Biomedical Centres. SDBTT have alsofunded a project officer post for the group and we hope to appoint to the post at UCLshortly.The group has been made aware of problems specific to the UK that make participationin European studies challenging, including long lag time between MREC agreement andlocal set up and variability in local sponsorship agreements. We hope to address thesein collaboration with the NCRI EORTC Liaison Officer.3-year strategyThe BTCSG’s three year strategy is to: • Increase proportion of brain tumour patients in UK that are included in high quality clinical studies. • Continue to work closely with the international research community to involve UK patients in available studies • Introduce novel surgical and radiotherapeutic technologies within well defined studies in good performance status high grade glioma patients -4-
  • Annual report 2007-8 • Define standard treatment protocols for patients with rare tumours in context of clinical studies in which biological end points can be measured • Identify issues in brain tumour patient carer groups and the means to address these • Develop systems for UK wide imaging based monitoring of response to treatmentPriorities for next year • Expansion of portfolio focusing on phase II studies. • Initiation of a national tumour genetics study in brain tumours. • A follow up meeting to discuss specific joint projects with the paediatric and TYA groups is planned for autumn 2008. • Contribute to an initiative to set up a brain tumour registry for the UK. • Appointment of a project officer post to support new initiativeDr Susan Short, ChairAppendix 1 -5-
  • Annual report 2007-82007/08 Publications and abstractsBurnet NG and Benson RJ. Central Nervous System Tumors. In: CancerRadiotherapy. Eds. Huddart RA and Murthy V, pp 245-278. Humana Press, Totowa,New Jersey, 2007. ISBN-13: 978-0-89603-831-8. Due for publication June 2008.Albertella MR, Loadman PM, Jones PH, Phillips RM, Rampling R, Burnet N, AlcockC, Anthoney A, Vjaters E, Dunk CR, Harris PA, Wong A, Lalani AS, Twelves CJ.Hypoxia-Selective Targeting by the Bioreductive Prodrug AQ4N in Patients with SolidTumors: Results of a Phase I Study. Clin Cancer Res 2008; 14(4): 1096-1104Ganesan D, Higgins JN, Harrower T, Burnet NG, Sarkies NJ, Manford M, PickardJD.Stent placement for management of a small parasagittal meningioma. J Neurosurg2008; 108(2): 377-81Higgins JN, Burnet NG, Schwindack CF, Waters A.severe brain edema caused by ameningioma obstructing cerebral venous outflow and treated with venous sinus stenting.J Neurosurg 2008; 108(2): 372-6Burnet NG, Lynch AG, Jefferies SJ, Price SJ, Jones PH, Antoun NM, Xuereb JH, UPohl. High grade glioma: imaging combined with pathological grade definesmanagement and predicts prognosis. Radiother Oncol 2007; 85: 371–378 [Epub 2007Nov 20]Price SJ, Jena R, Green HA, Kirkby NF, Lynch AG, Coles CE, Pickard JD, GillardJH, Burnet NG. ; 19(8): 577-587 [Epub 2007 July 11 ] Early radiotherapy doseresponse and lack of hypersensitivity effect in normal brain tissue: a sequential dynamicsusceptibility imaging study of cerebral perfusion. Clin Oncol 2007Foweraker KL, Burton KE, Maynard SE, Jena R, Jefferies SJ, Laing RJ, Burnet NG,Skull Base Surgery And Neurosurgery Collaborators. High-dose Radiotherapy inthe Management of Chordoma and Chondrosarcoma of the Skull Base and CervicalSpine: Part 1 - Clinical Outcomes. Clin Oncol 2007; 19(7): 509-16 [Epub 2007 May 23]Horan G, Whitfield GA, Burton KE, Burnet NG, Jefferies SJ. Fractionated ConformalRadiotherapy in Vestibular Schwannoma: Early Results from a Single Centre. ClinOncol 2007; 19(7): 517-22 [Epub 2007 Apr 2]West CML, Elliott RM, Burnet NG. The Genomics Revolution and Radiotherapy. ClinOncol 2007; 19: 470 – 480 [Epub Apr 5]Price SJ, Jena R, Burnet NG, Carpenter TA, Pickard JD, Gillard JH. Predictingpatterns of glioma recurrence using diffusion tensor imaging. Eur Radiol 2007; 17:1675-1684Hamilton W, Kernick D. Clinical features of primary brain tumours: a case-control studyusing electronic primary care records. British Journal General Practice 2007;57:695-699. -6-
  • Annual report 2007-8HR Jäger, A Waldman, C Benton, N Fox, JH Rees. Differential chemosensitivity oftumour compartments in a malignant oligodendrogliomas: assessment with diffusion-weighted, perfusion-weighted and serial volumetric MR imaging. Am J Neuroradiol2005; 26: 274-278DJ Tozer, HR Jäger, N Danchaivijitr, CE Benton, PS Tofts, JH Rees and ADWaldman. Apparent Diffusion Coefficient Histograms may predict Low Grade GliomaSubtype. NMR in Biomedicine 2007; 20: 49-57PS Tofts, CE Benton, R Weil, DJ Tozer, DR Altmann, HR Jäger, AD Waldman andJH Rees. Quantitative analysis of whole tumour Gd enhancement histograms predictsmalignant transformation in low-grade gliomas. J Magn Res Imaging 2007;25:208-214N Danchaivijitr, AD Waldman, DJ Tozer, CE Benton, G Brasil Caseiras, PS Tofts,JH Rees and HR Jäger Longitudinal Perfusion-Weighted MR Imaging in Patients withLow Grade Gliomas: Do Changes in rCBV Measurements Predict MalignantTransformation? Radiology 2008;247:170-8Gisele Brasil Caseiras, John S. Thornton, Tarek Yousry, Christopher Benton,Jeremy Rees, Adam D. Waldman, H. Rolf Jäger Inclusion or Exclusion of intratumoralvessels in relative Cerebral Blood Volume (rCBV) characterization in low grade gliomas:Does it make a difference? Accepted by AJNR -7-