David Ashley

Overview:

Dr. Ashley's primary research focus is laboratory based, investigating the role of immunotherapy as a novel approach to the treatment of tumors of the central nervous system (CNS). Since beginning his appointment at the faculty level at Duke in August of 1995 his activities have centered on two main areas of investigation. The first involves both in vivo and in vitro studies of the use of molecular therapeutics to target a CNS tumor associated antigen. The second area of interest comprises a detailed analysis of the role of TGF beta, a protein messenger produced by tumors of the CNS, both in the pathogenesis of disease and as a possible target for immunotherapy.

In addition to his laboratory role Dr. Ashley is involved in the design and application of a variety of clinical research protocols in the treatment of children with malignant brain tumors.

Positions:

Rory David Deutsch Professor of Neuro-Oncology

Neurosurgery
School of Medicine

Professor of Neurosurgery

Neurosurgery
School of Medicine

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Professor in Pediatrics

Pediatrics, Neurology
School of Medicine

Professor in Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

F.R.A.C.P. 1993

Royal Australian College of Physicians

M.B.B.S. 1994

University of Melbourne (Australia)

Ph.D. 1998

University of Melbourne (Australia)

Grants:

LGG-14C03: A Phase III study comparing two carboplatin containing regimens for children and young adults with previously untreated low grade glioma

Administered By
Duke Cancer Institute
Awarded By
Ann & Robert H. Lurie Children's Hospital of Chicago
Role
Principal Investigator
Start Date
End Date

A Randomized, Multicenter, Phase 2 Study of PVSRIPO alone or in combination with Lomustine

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Recombinant Attenuated Poliovirus Immunization Vectors Targeting H3.3(K27M) in DIPG

Administered By
Neurosurgery, Neuro-Oncology Clinical Research
Role
Co Investigator
Start Date
End Date

SJMB12: A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma

Administered By
Pediatrics, Hematology-Oncology
Awarded By
St. Jude Children's Research Hospital
Role
Principal Investigator
Start Date
End Date

Publications:

Primary brain tumors admitted to the neurological intensive care unit: a single institution observational study

Authors
Kang, J; Swisher, C; Kirkpatrick, J; Herndon, J; Lipp, E; Thomas, L; Johnson, M; Ashley, D; Desjardins, A; Randazzo, D; Friedman, H; Peters, K
MLA Citation
Kang, Jennifer, et al. “Primary brain tumors admitted to the neurological intensive care unit: a single institution observational study.” Neurology, vol. 92, no. 15, LIPPINCOTT WILLIAMS & WILKINS, 2019.
URI
https://scholars.duke.edu/individual/pub1402278
Source
wos
Published In
Neurology
Volume
92
Published Date

Tailored NEOadjuvant epirubicin, cyclophosphamide and Nanoparticle Albumin-Bound paclitaxel for breast cancer: The phase II NEONAB trial-Clinical outcomes and molecular determinants of response.

BACKGROUND: This study evaluated the feasibility of achieving high response rates in stage II or III breast cancer by tailoring neoadjuvant therapy using clinical and histopathological features and the Oncotype DX Breast Recurrence Score. Genomic determinants of response and resistance were also explored. PATIENTS AND OUTCOME MEASURES: Fifty-one patients were enrolled. The primary cohort comprised 40 patients: 15 human epidermal growth factor receptor type 2 (HER2)-amplified; 15 triple-negative (TNBC); and ten hormone receptor (HR)-positive, HER2-non-amplified tumours; with recurrence scores ≥25. Patients were treated with epirubicin and cyclophosphamide, followed by nab-paclitaxel, with the addition of trastuzumab if HER2-amplified. The primary endpoint was pathological complete response (pCR) in the breast. Pre- and post-treatment tumour samples underwent variant burden, gene and gene pathway, mutational signature profile and clonal evolution analyses. RESULTS: The pCR rates were: overall 55% (n = 22), HER2-amplified 80% (n = 12), triple-negative 46% (n = 7) and HR-positive, HER2-non-amplified 30% (n = 3). Grade 3 or 4 adverse events included febrile neutropenia (8%), neutropenia (18%), sensory neuropathy (5%), deranged transaminases (5%), fatigue (2%), diarrhoea (2%), and pneumothorax (2%). Molecular analyses demonstrated strong similarities between residual disease and matched primary tumour. ATM signalling pathway alterations and the presence of a COSMIC Signature 3 implied the majority of tumours contained some form of homologous repair deficiency. ATM pathway alterations were identified in the subset of TNBC patients who did not achieve pCR; Signature 3 was present in both pCR and non-pCR subgroups. Clonal evolution analyses demonstrated both persistence and emergence of chemoresistant clones. CONCLUSIONS: This treatment regime resulted in a high rate of pCR, demonstrating that tailored neoadjuvant therapy using a genomic recurrence score is feasible and warrants further investigation. Molecular analysis revealed few commonalities between patients. For TNBC future clinical gains will require precision medicine, potentially using DNA sequencing to identify specific targets for individuals with resistant disease. TRIAL REGISTRATION: Clinicaltrials.gov NCT01830244.
Authors
Murphy, C; Muscat, A; Ashley, D; Mukaro, V; West, L; Liao, Y; Chisanga, D; Shi, W; Collins, I; Baron-Hay, S; Patil, S; Lindeman, G; Khasraw, M
URI
https://scholars.duke.edu/individual/pub1405542
PMID
30763338
Source
pubmed
Published In
Plos One
Volume
14
Published Date
Start Page
e0210891
DOI
10.1371/journal.pone.0210891

A randomized phase 2 trial of veliparib (V), radiotherapy (RT) and temozolomide (TMZ) in patients (pts) with unmethylated MGMT (uMGMT) glioblastoma (GBM): Feasibility and safety outcomes (the VERTU study).

Authors
Khasraw, M; McDonald, KL; Rosenthal, M; Lwin, Z; Ashley, DM; Wheeler, H; Barnes, E; Koh, E-S; Foote, MC; Buckland, M; Fisher, L; Leonard, R; Hall, M; Yip, S; Simes, J
MLA Citation
Khasraw, Mustafa, et al. “A randomized phase 2 trial of veliparib (V), radiotherapy (RT) and temozolomide (TMZ) in patients (pts) with unmethylated MGMT (uMGMT) glioblastoma (GBM): Feasibility and safety outcomes (the VERTU study)..” Journal of Clinical Oncology, vol. 36, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2018, pp. 2045–2045. Crossref, doi:10.1200/jco.2018.36.15_suppl.2045.
URI
https://scholars.duke.edu/individual/pub1405618
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
36
Published Date
Start Page
2045
End Page
2045
DOI
10.1200/jco.2018.36.15_suppl.2045

Tailored neoadjuvant epirubicin and cyclophosphamide (EC) and nanoparticle albumin bound (nab)-paclitaxel for newly diagnosed breast cancer (BC).

Authors
Khasraw, M; Mukaro, VR; West, L; Brandt, C; Woollett, AM; Edwards, M; Spokes, R; Mitchell, G; Prince, K; Hayes, TM; Collins, IM; Guminski, AD; Baron-Hay, SE; Olesen, IH; Bryan, J; Bowles, S; Wong, SF; Ashley, DM; Patil, S
MLA Citation
Khasraw, Mustafa, et al. “Tailored neoadjuvant epirubicin and cyclophosphamide (EC) and nanoparticle albumin bound (nab)-paclitaxel for newly diagnosed breast cancer (BC)..” Journal of Clinical Oncology, vol. 33, no. 15, AMER SOC CLINICAL ONCOLOGY, 2015.
URI
https://scholars.duke.edu/individual/pub1405651
Source
wos
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
33
Published Date

A meta-analysis of antiangiogenic therapy for glioblastoma (GBM).

Authors
Khasraw, M; Ameratunga, M; Lassman, AB; Ashley, DM; Wheeler, H; Pavlakis, N
MLA Citation
Khasraw, Mustafa, et al. “A meta-analysis of antiangiogenic therapy for glioblastoma (GBM)..” Journal of Clinical Oncology, vol. 32, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2014, pp. 2047–2047. Crossref, doi:10.1200/jco.2014.32.15_suppl.2047.
URI
https://scholars.duke.edu/individual/pub1405643
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
32
Published Date
Start Page
2047
End Page
2047
DOI
10.1200/jco.2014.32.15_suppl.2047