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Poster display

1318 - CamBMT1: A proof-of-principle phase 1b / randomised phase 2 study of afatinib penetration into brain metastases (mets) for patients undergoing neurosurgical resection, both with and without prior low-dose, targeted radiotherapy

Date

10 Oct 2016

Session

Poster display

Presenters

Richard Baird

Citation

Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368

Authors

R. Baird1, J. Garcia-Corbacho1, N. Ramenatte2, A. Jonson3, S. Ahmad4, D. Smith5, W. Qian3, S. Kumar3, C. Linossi3, T. Matys6, M. Graves6, D. Jodrell3, C. Caldas7, S. Pacey3, G. Whitfield8, A. Chalmers9, R. Jena4, S. Price10, S. Jefferies4, C. Watts10

Author affiliations

  • 1 Breast Cancer Research Unit, Addenbrookes Hospital Box 97, Cambridge Cancer Centre, CB2 0QQ - Cambridge/GB
  • 2 Cambridge Clinical Trials Unit - Cancer Theme, Addenbrookes Hospital Box 279, Cambridge Cancer Centre, CB2 0QQ - Cambridge/GB
  • 3 Early Phase Clinical Trials Team, Addenbrookes Hospital Box 279, Cambridge Cancer Centre, CB2 0QQ - Cambridge/GB
  • 4 Neuro-oncology Team, R4, Addenbrookes Hospital Box 193, Cambridge Cancer Centre, CB2 0QQ - Cambridge/GB
  • 5 Cruk Cambridge Institute Pk/bioanalytics Core Facility, Cambridge Cancer Centre, CB2 0RE - Cambridge/GB
  • 6 Department Of Radiology, University Of Cambridge, Cambridge Cancer Centre, CB2 0QQ - Cambridge/GB
  • 7 Cruk Cambridge Institute, Cambridge Cancer Centre, CB2 0RE - Cambridge/GB
  • 8 Neuro-oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 9 Cruk Beatson Institute, University of Glasgow, G61 1BD - Glasgow/GB
  • 10 Divison Of Neurosurgery, Dept Clinical Neurosciences, University Of Cambridge, Cambridge Cancer Centre, CB2 0QQ - Cambridge/GB
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Resources

Abstract 1318

Background

Failure of drugs to cross the blood brain barrier (BBB) can be a major reason for treatment failure for patients with brain tumours. For most patients who don't respond to treatment, it is not known whether this is due to inadequate drug concentrations in the tumour, or due to drug resistance. Preliminary data suggest that low-dose radiotherapy may disrupt the BBB, and could facilitate increased drug delivery into brain tumours. Afatinib is a potent, irreversible inhibitor of EGFR / HER2 / HER4 and takes approximately 8 days to achieve steady-state concentrations in cancer patients. CamBMT1 has been designed to investigate the delivery of afatinib into brain mets and whether this might be enhanced by low dose-radiotherapy.

Trial design

Study population: patients with operable brain mets from breast or lung primaries for whom neurosurgical resection would be standard of care. After a phase 1b safety run-in, the phase 2 part of the trial randomises patients (n = 60) into 3 pre-operative arms:

Arm 1: afatinib alone for 11 days, then neurosurgery on day 12
Arm 2: afatinib for 11 days plus a single 2 Gy fraction on day 10, then neurosurgery on day 12
Arm 3: afatinib for 11 days plus a single 4 Gy fraction on day 10, then neurosurgery on day 12

The primary endpoint is to compare steady-state afatinib concentration in resected brain mets, following afatinib administered alone, or in combination with radiotherapy (2 Gy or 4 Gy). Afatinib concentrations are measured in the resected brain mets and in plasma. Secondary endpoints: safety of afatinib administration in combination with radiotherapy; and multi-sequence MRI (optional) to detect changes in perfusion, vascular density, blood-brain-barrier permeability and interstitial pressure. Exploratory endpoints: molecular profiling of resected brain mets, for comparison with paired primary lung and breast cancers; the study of patient-derived xenografts. CamBMT1 is a multi-centre trial now opening at additional Experimental Cancer Medicine Centres, and is funded by Cancer Research UK, the Brain Tumour Charity and Boehringer-Ingelheim.

Clinical trial identification

EudraCT Number: 2013-002398-23

Legal entity responsible for the study

Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge

Funding

Cancer Research UK The Brain Tumour Charity Boehringer-Ingelheim

Disclosure

All authors have declared no conflicts of interest.

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