Clinical research on brain and CNS cancer

Over 4,000 people are diagnosed with new cases of brain or central nervous system (CNS) cancer every year in the UK. Glioblastomas are the most common and aggressive form of brain tumour in adults. Research at the CRUK Cambridge Centre is focused on understanding the different types of brain tumours that develop in both adults and children, finding the most effective ways of diagnosing brain tumours as early as possible, developing new treatments, and monitoring how tumours are responding to treatment.
 
A trial using dyes to guide surgery
The Cambridge Cancer Centre is coordinating a number of clinical trials for adults and children with cancer of the brain or spinal cord. One of these trials is testing a new tool to help surgeons remove as much of brain tumour as possible and potentially improve the survival rates of patients. Patients with glioblastoma are given a drink containing a dye before their operation, which makes. The dye makes the tumour cells glow pink under ultra-violet light. This allows the surgeon to distinguish tumour from normal brain allowing more tumour to be removed while improving patient safety so during surgery the surgeon can see the tumour cells more clearly and remove as much of the tumour as possible. Discs with a drug that kills tumour cells are then implanted in the space left after the tumour has been removed, to target any tumour cells left behind.

Tumour heterogeneity, growth and evolution
We have recently developed a real-time multiple sampling scheme to interrogate high-grade glioma during surgery. FGMS (Fluorescence-Guided Multiple Sampling) is based on fluorescence-guided resection technology to obtain spatially distinct tumour biopsies from individual tumours in real time, during cytoreductive surgery Figure 1.1. We can use these data to dissect intra-tumour heterogeneity, identify clonal diversity and infer tumour evolution Figure 1.2. 
 

Figure 1.1 We have developed a real-time multiple sampling scheme to interrogate high-grade glioma during surgery. FGMS (Fluorescence-Guided Multiple Sampling) is based on fluorescence-guided resection technology to obtain spatially distinct tumour biopsies from individual tumours in real time.

Figure 1.2 Reconstruction of GB progression in time and space: The combination of sampling information (A), reconstructed tumor phylogeny (B), gene expression profiles, and molecular clock data enables temporal and spatial reconstruction of tumor ontogeny (C)
 
Little is known about the impact of intra-tumour heterogeneity on tumour evolution, growth and the consequences of such heterogeneity on the emergence of resistant disease. This is an important problem in brain tumour research because it is the emergence of recurrent treatment-resistant disease that kills patients and it is variability in this biological process that is responsible for variation between individual patients.
 
Current open trials in Cambridge
 
The table below lists the current open trials for brain and CNS cancer coordinated by the Cambridge Cancer Trials Centre (last updated January 2016).
 
Trial name Trial description Contact
CamBMT1 An early phase trial Dr Richard Baird
GALA-BIDD Improving the Intra-operative Diagnosis of High-Grade Glioma using a Fluorescence Biomarker Dr Colin Watts
Hydroxychloroquine Trial (HCQ) A randomised phase 2 trial investigating the additional benefit of hydroxychloroquine(HCQ) to short course radiotherapy (SCRT) in patients aged 70 years and older with high grade gliomas (HGG) Dr Colin Watts
MMMR Brain Understanding Brain Tumour Heterogenity using Multimodal MR Imaging of Tumour Pathology: Developing MR Methodologies Mr Stephen Price
MR characterisation of invasive phenotypes in GBMs Magnetic Resonance Imaging to Characterise Invasive Phenotypes in Cerebral Gliomas Mr Stephen Price
Phase 1 trial of olaparib with temozolomide in relapsed glioblastoma (OPARATIC) A Cancer Research UK Phase I trial of olaparib (AZD2281), an oral PARP Inhibitor, in combination with extended lowdose oral temozolomide in patients with relapsed glioblastoma Dr Sarah Jefferies
Stem Cells Finding Stem Cells in The Brain. To use tissue taken during elective neuro surgical operations  to derive human stem cells. The cells are used to study whether stem cells exist in the diseased human brain and how human adult stem cells divide grow and migrate in the context of pathology such as injury, tumours and degeneration.  Dr Colin Watts
 
If you would like further information about how to take part in any of the clinical trials listed here, please talk to your cancer specialist as patients usually need to be referred by their doctor.

Cambridge Cancer Trials Centre contact for head and neck, and CNS cancer trials:  Dr Sarah Jefferies