Brain Tumor CSG 2007-8 Annual Report


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Brain Tumor CSG 2007-8 Annual Report

  1. 1. Annual report 2007-8 NCRI Brain Tumour Clinical Studies Group Introduction The Brain Tumour Clinical Studies Group (BTSG) has continued to work towards increasing the range of clinical studies available for brain tumour patients in the UK. In the past year we have also begun to address some of the long term issues underlying poor recruitment in rare tumour types, identified new funding sources to help support brain tumour studies and forged closer links with the paediatric and teenage and young adult groups. The newly set up expertise based subgroups of the BTSG have all been very active in the last year and several new study ideas are being developed through them. Membership and structure Since the progress review in February 2007, five expertise based subgroups have been set up to address research issues in imaging, translational research, palliative care, technology development and use of new agents in brain tumours. These have been very active in the last year and several new study ideas have been brought forward. Most notably the Novel Agents Subgroup has been involved in the design of 2 new phase I studies in GBM and CNS lymphoma respectively and a phase II study using a novel repair inhibitor with radiation in poor prognosis GBM. The Palliative Care Subgroup has also begun a pilot study addressing the needs of carers of brain tumour patients. The Imaging Subgroup has been very active in exploring means of co-ordinating the approach to use of novel imaging in clinical studies and are preparing a major review of this subject. The Surgical Technology Subgroup is focusing on designing a study to assess the utility of convection enhanced delivery of cytotoxic agents. Portfolio and accrual There are 3 trials currently open in the Group’s portfolio; all are in set up (see Table I below). 2 further trials are open in collaboration with the Radiotherapy and Lung CSG’s, OSCAR and TACTIC respectively. New trials under discussion include a tumour genetics study and several phase II studies testing the effect of novel agents (see below). 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. The translational study linked to the BR12 trial is ongoing and preliminary data have been presented. The first clinical data will be available later in 2008. The Group has also collaborated with the EORTC on a randomised trial examining the role of whole brain radiotherapy after resection or radiosurgery for patients with 1-3 brain metastases. Although recruitment began slowly, increased participation from new centres enabled more rapid recruitment during 2006 and 2007 and the trial was closed in October 2007. A further phase III EORTC study addressing the effect of dose dense temozolomide compared to standard dose temozolomide in newly diagnosed glioblastoma multiforme patients is open in selected centres and is recruiting extremely rapidly, with several UK centres contributing large patient numbers. The Group has joined the EORTC in the development and implementation of a low-grade glioma trial, which compares Temozolomide versus radiotherapy in patients with progressive grade II astrocytomas, - 1 -
  2. 2. Annual report 2007-8 oligodendrogliomas and mixed tumours (EORTC 22033 – 26033), which will open shortly. The major trial in set up is the CATNON (BR14/TATA trial), to examine the role of chemotherapy in patients with grade III astrocytoma (non1p,19q deleted anaplastic glioma). This study will be a major collaborative study between MRC/EORTC and RTOG with a substantial translational component. Table 1: Brain Tumour CSG Portfolio Acronym Title PI(s) Status BR11 Adjuvant procarbazine, CCNU and vincristine chemotherapy in patients with highly anaplastic oligodendroglioma (in collaboration with the EORTC). Closed BR12 Temozolomide vs PCV chemotherapy in the treatment of recurrent malignant glioma Prof Michael Brada Closed BR14 A randomised controlled trial of temozolomide as adjuvant and/or concurrent treatment in anaplastic (WHO grade III) glioma in Set-up EORTC 22033-26033 - Low grade glioma trial (BR13) Primary chemotherapy with temozolomide vs. radiotherapy in patients with low grade gliomas with stratification for genetic 1p loss: a phase III study Dr Jeremy Rees in Set-up EORTC 22952 No Radiotherapy versus Whole Brain Radiotherapy for 1 to 3 Brain Metastases from Solid Tumor after Surgical Resection or Radiosurgery. A Randomized Phase III Trial. Dr R Soffietti Closed EORTC 26052 Phase III Trial comparing Conventional Adjuvant Temozolomide with Dose Intensive Temozolomide in Patients with Newly Diagnosed Glioblastoma Dr Sara Erridge in Set-up Neo-adjuvant Carboplatin Trial Multicentre, Phase II Study of Carboplatin pre-irradiation in patients with primary glioblastoma multiforme following biospy Closed The 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 incidence cases. All were to RCTs. Publications for the reporting year can be found in Appendix 1. - 2 -
  3. 3. Annual report 2007-8 Table 2: Subgroup activity Sub-group Current priorities Studies under discussion Palliative care QOL in brain tumour carers Interventions for treatment related fatigue Questionnaire study of carers of glioma patients Complementary therapy intervention for RT related fatigue Translational research BR12 translational study Novel agents in meningioma New approaches to Schwannoma Ongoing In vitro studies with anti- tubulin agent ongoing Phase II study of anti- angiogenic agent Imaging Defining role of new imaging techniques as biomarkers in clinical studies Co-ordinating assessment of image data across research active centres Bolt-on imaging study to EORTC 26052 New agents Use of DNA repair inhibitors as radiosenitisers Anti-angiogenic agents with standard treatment of HGG Use of MRI biomarkers Phase 0 trials to investigate PD and biomarker endpoints Phase II study of RT + Parp inhibitor for elderly/poor performance status GBM patients Phase I study of HD Methotrexate with Glucarpidase in CNS lymphoma Trials in development The trials in development are summarized in Table 3 below. Table 3: Studies under development Study PI Design/status Radiotherapy with Adjuvant Chemotherapy for Adults with Intracranial Primitive Neuro- ectodermal Tumour (PNET) (CAPNET) Roger Taylor Single arm phase II Submitted to CTAAC - 3 -
  4. 4. Annual report 2007-8 PARP inhibitors with radiotherapy in poor prognosis GBM Anthony Chalmers Phase II Under development in new agents group Radiosurgery and Laptinib in HER2+ breast cancer brain metastases Lucy Brazil Randomised phase II Under discussion with GSK Quality of life issues in carers of brain tumour patients Angela Costello Pilot questionnaire study Palliative Care Subgroup Meetings A major focus in the last year has also been addressing poor access to studies in young adults with brain tumours and forging closer links with the paediatric oncology groups. A successful one-day meeting was held in December 2007 including a series of talks and discussion to begin to plan a future joint agenda. A further more focussed meeting is planned for 2008 and an opinion document will be published on behalf of those contributing to the first meeting. Collaborations The Group is collaborating in two national brain metastases trials. The OSCAR trial, developed with the Radiotherapy CSG, is assessing the role of radiotherapy in poor prognosis patients with multiple brain metastases from non-small cell lung cancer and will randomise patients between best supportive care and whole brain irradiation. The TACTIC trial, developed in collaboration with the Lung CSG, is assessing the value of Erlotinib (Tarceva) in addition to whole brain radiotherapy using a randomised phase II trial 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 Study Groups. Other activities The Group has been aware of the problems inherent in clinical research in rare tumour types in accessing local resources to support study entry including data management, research nurse and research administration support. Following discussions at CSG meetings an initiative has been agreed with CRUK and The Samantha Dixon Brain Tumour Trust (SDBTT) to make targeted funding available for clinical research in to brain tumours through the Comprehensive Biomedical Centres. SDBTT have also funded a project officer post for the group and we hope to appoint to the post at UCL shortly. The group has been made aware of problems specific to the UK that make participation in European studies challenging, including long lag time between MREC agreement and local set up and variability in local sponsorship agreements. We hope to address these in collaboration with the NCRI EORTC Liaison Officer. 3-year strategy The 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 - 4 -
  5. 5. Annual report 2007-8 • Introduce novel surgical and radiotherapeutic technologies within well defined studies in good performance status high grade glioma patients • 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 treatment Priorities 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 initiative Dr Susan Short, Chair - 5 -
  6. 6. Annual report 2007-8 Appendix 1 2007/08 Publications and abstracts Burnet NG and Benson RJ. Central Nervous System Tumors. In: Cancer Radiotherapy. 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, Alcock C, 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 Solid Tumors: Results of a Phase I Study. Clin Cancer Res 2008; 14(4): 1096-1104 Ganesan D, Higgins JN, Harrower T, Burnet NG, Sarkies NJ, Manford M, Pickard JD.Stent placement for management of a small parasagittal meningioma. J Neurosurg 2008; 108(2): 377-81 Higgins JN, Burnet NG, Schwindack CF, Waters A.severe brain edema caused by a meningioma obstructing cerebral venous outflow and treated with venous sinus stenting. J Neurosurg 2008; 108(2): 372-6 Burnet NG, Lynch AG, Jefferies SJ, Price SJ, Jones PH, Antoun NM, Xuereb JH, U Pohl. High grade glioma: imaging combined with pathological grade defines management and predicts prognosis. Radiother Oncol 2007; 85: 371–378 [Epub 2007 Nov 20] Price SJ, Jena R, Green HA, Kirkby NF, Lynch AG, Coles CE, Pickard JD, Gillard JH, Burnet NG. ; 19(8): 577-587 [Epub 2007 July 11 ] Early radiotherapy dose response and lack of hypersensitivity effect in normal brain tissue: a sequential dynamic susceptibility imaging study of cerebral perfusion. Clin Oncol 2007 Foweraker KL, Burton KE, Maynard SE, Jena R, Jefferies SJ, Laing RJ, Burnet NG, Skull Base Surgery And Neurosurgery Collaborators. High-dose Radiotherapy in the Management of Chordoma and Chondrosarcoma of the Skull Base and Cervical Spine: 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 Conformal Radiotherapy in Vestibular Schwannoma: Early Results from a Single Centre. Clin Oncol 2007; 19(7): 517-22 [Epub 2007 Apr 2] West CML, Elliott RM, Burnet NG. The Genomics Revolution and Radiotherapy. Clin Oncol 2007; 19: 470 – 480 [Epub Apr 5] Price SJ, Jena R, Burnet NG, Carpenter TA, Pickard JD, Gillard JH. Predicting patterns of glioma recurrence using diffusion tensor imaging. Eur Radiol 2007; 17: 1675-1684 Hamilton W, Kernick D. Clinical features of primary brain tumours: a case-control study using electronic primary care records. British Journal General Practice 2007;57:695-699. - 6 -
  7. 7. Annual report 2007-8 HR Jäger, A Waldman, C Benton, N Fox, JH Rees. Differential chemosensitivity of tumour compartments in a malignant oligodendrogliomas: assessment with diffusion- weighted, perfusion-weighted and serial volumetric MR imaging. Am J Neuroradiol 2005; 26: 274-278 DJ Tozer, HR Jäger, N Danchaivijitr, CE Benton, PS Tofts, JH Rees and AD Waldman. Apparent Diffusion Coefficient Histograms may predict Low Grade Glioma Subtype. NMR in Biomedicine 2007; 20: 49-57 PS Tofts, CE Benton, R Weil, DJ Tozer, DR Altmann, HR Jäger, AD Waldman and JH Rees. Quantitative analysis of whole tumour Gd enhancement histograms predicts malignant transformation in low-grade gliomas. J Magn Res Imaging 2007;25:208-214 N Danchaivijitr, AD Waldman, DJ Tozer, CE Benton, G Brasil Caseiras, PS Tofts, JH Rees and HR Jäger Longitudinal Perfusion-Weighted MR Imaging in Patients with Low Grade Gliomas: Do Changes in rCBV Measurements Predict Malignant Transformation? Radiology 2008;247:170-8 Gisele Brasil Caseiras, John S. Thornton, Tarek Yousry, Christopher Benton, Jeremy Rees, Adam D. Waldman, H. Rolf Jäger Inclusion or Exclusion of intratumoral vessels in relative Cerebral Blood Volume (rCBV) characterization in low grade gliomas: Does it make a difference? Accepted by AJNR - 7 -