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      Research Statement

      Current Research

      I am the Clinical Director of both the N. Ireland Cancer Trials Network and its Co-ordinating Centre, and also Deputy lead of the Belfast Experimental cancer Medicine Centre.

      I developed in 2001 and since then have led the early phase and lower GI cancer clinical trials programmes in N. Ireland. 

      I work as a medical oncologist in gastro-intestinal cancer (mainly colorectal cancer but also in small bowel cancer and peritoneal malignancies) and conduct biological and translational research in these diseases.

      I am the currently Chair of the UK National Cancer Research Institute Colorectal Cancer Clinical Studies Group.

      I am Chief Investigator on a variety of local, national and international phase I, II and III cancer clinical trials. This includes the ALM201 phase I trial, which investigates a novel anti-angiogenic agent which is the first ever anti-cancer drug developed entirely in N. Ireland and which is twinned with an angiogenesis response signature which is being developed as a companion diagnostic.

      I chair the International Rare Cancer Initiative Small Bowel Adenocarcinoma Working Group, and am CI of Global BALLAD, the first ever adjuvant randomised controlled trial in this disease.

      I am also CI of the adjuvant colorectal cancer trial in Add-Aspirin, an international phase III trial programme in CRC but also in breast, gastro-oesophageal and prostate cancer. 

      I have a major interest in personalised medicine, and am co-CI on the FOCUS4 trial in metastatic colorectal cancer which has been funded by Cancer Research UK and the Medical Research Council as the flagship trial in precision medicine in oncology in the UK.   

       

      Future Research Plans

       1. I will lead the clinical development of QUB science building on our current achievements. This will include:

      (i) leading ALM201 through its current monotherapy trial into combination studies and biomarker-guided use in colorectal cancer.

      (ii) leading the novel agent CV6-168 as the second anti-cancer drug developed in N. Ireland into the clinic.

      (iii) building on our recent successful Wellcome Trust SDD Award to bring our  QUB-developed FLIP inhibitor to the clinic in a biomarker–guided First-in-Human trial.

      (iv) leading QUB death signalling and cdc7 bioscience into the clinic through partnership with Cancer Research UK, MedImmune and Lilly.

      (v) I will use my experience of these to bring other QUB-developed agents and biomarkers into the clinic.

       2. Through my leadership in the national/international trials and stratified medicine research programmes in FOCUS-4, Add-Aspirin and S:CORT, I will lead advances in the treatment  of colorectal cancer and our understanding of its biology.

       3. Having developed the first ever trial in adjuvant therapy in small bowel adenocarcinoma, I will develop international trials in the metastatic setting and explore the biology of this rare cancer.

       4. I will build our early phase trials programme through collaboration with investigators, Cancer Research UK and pharma.

      Other

      CANCER CLINICAL TRIALS

      1. I am the co-Chief Investigator (with Prof Tim Maughan) for the FOCUS 4 randomized trial of molecular selection and novel agents in first-line metastatic colorectal cancer. I am co-CI of the FOCUS4-B trial of aspirin in PIK3CA exon 9 and 20 mutant metastatic colorectal cancer due to open in Spring 2016. I am also co-CI of the planned FOCUS4-E trial of a PD-L1 inhibitor in patients with mismatch repair deficient CRC due to open in late 2016.

      2. I am the Co-Chief Investigator of the phase I trial component of MERCURIC. This is a phase I/II/III trial programme exploring use of the MEK1/2 inhibitor PD-0325901 with the cMET inhibitor PF-02341066 in patients with KRAS mutant and KRAS wild-type (with aberrant c-MET) metastatic colorectal cancer. Dr S van Schaeybroeck is the overall lead for this €6 million programme grant from the European Union Framework Programme 7. The phase I trial opened in December 2014.                                           

      3. I am the Chief Investigator of the First-in-Human phase I open-label multicentre dose-escalation study of subcutaneous ALM201 in patients with advanced, solid tumours, with an expansion cohort in patients with biomarker-selected advanced ovarian cancer. This trial is led from Belfast, includes development of a companion diagnostic under Prof Kennedy and opened in July 2015.                                                                                                                   

      4. I am the Chief Investigator of the BALLAD trial (A Global Study To Evaluate The Potential Benefit Of Adjuvant Chemotherapy For Small Bowel Adenocarcinoma). The protocol has received all regulatory approvals and opened in October 2015. This trial is part of the portfolio of the International Rare Cancers Initiative.                                                           

      5. I am part of an international consortium led by the MRC Clinical Trials Unit that has developed the Add Aspirin international phase III double-blind placebo-controlled randomized trial of adjuvant aspirin for preventing recurrence and improving survival in patients with early stage common solid tumours. This includes breast cancer, gastro-oesophageal cancer, colorectal cancer and NSCLC and opened in October 2015. I am the global PI for the adjuvant colorectal cancer trial.                                                                       

      6. I am the Chief Investigator of the First-in-Human adaptive phase I trial of MEDI3039 in adult patients with cancer. This is being developed by Cancer Research UK. This trial will be led from Belfast and involves also the Newcastle, Manchester and UCL ECMCs.                                                                                                             

      7. I am the Chief Investigator of the First-in-Human phase I trial of LY3177833 Cdc7 inhibitor in adult patients with cancer. This is being developed by Cancer Research UK. This trial will be led from Belfast and involves also the Newcastle, Glasgow and Edinburgh ECMCs.                                                                                                                

      8. I am local PI on the following open or pending trials in NICTN:

      (i) NSCCG: National Study on Colorectal Cancer Genetics.

      (ii) A CR-UK adaptive phase I clinical trial of AZD4024 with combination agents.

      (iii) TAX-TORC: A phase I/II trial of weekly paclitaxel with the mTORC1/C2 inhibitor AZD2014.   

      (iv) Vit-D CRC: A Randomised Double Blind Placebo-Controlled Clinical Trial of a Single Oral Cholecalciferol Treatment Against Surrogate End Point Biomarkers in Colon Cancer Patients.

      (v) CAPITAL - a phase I/II study of capecitabine plus aflibercept in elderly patients with unresectable metastatic colorectal cancer.                                

      9. I am local AI on the following open or pending trials in NICTN:

      (i) PULMICC: a randomised phase II feasibility trial of resection of colorectal pulmonary metastases.

      (ii) InterAACT trial in relapsed or metastatic anal carcinoma.

      10. I was local PI on the following trials in NICCTU/NICTN, now closed:

      (i) A Cancer Research UK first in human phase I trial of the intravenous PARP Inhibitor AG014699 with Temozolomide          

      (ii) Scotroc-3: Phase Ib trial of Docetaxel/Carboplatin administered with Tarceva to patients with newly diagnosed epithelial ovarian cancer, fallopian tube cancer and primary peritoneal cancer

      (iii) WARP: A multicentre prospective randomised controlled trial of thrombosis prophylaxis with Warfarin in cancer patients with central venous catheters

      (iv) CONFIRM-1: A randomised double-blind placebo-controlled phase III study in patients with metastatic colorectal cancer receiving first-line chemotherapy with FOLFOX4 and PTK/ZK or placebo  

      (v) CONFIRM-2: A randomised double-blind placebo-controlled phase III study in patients with metastatic colorectal cancer receiving second-line chemotherapy with FOLFOX4 and PTK/ZK or placebo

      (vi) ACancer Research UK first in human phase I trial of oral 667-Coumate (a sulphatase inhibitor) in postmenopausal women with locally advanced or metastatic breast cancer

      (vii) An EORTC phase I trial of OSI-7904L in combination with Oxaliplatin in patients with advanced colorectal cancer.

      (viii) An open-label, randomised, multiple dose phase II study to assess the pharmacokinetics of ZD4054 in patients with metastatic prostate cancer.

      (ix) A phase I study to assess the safety and tolerability of ZD6474 in combination with FOLFIRI as first or second line therapy in patients with metastatic colorectal cancer.

      (x) A phase II trial of the intravenous PARP inhibitor AG014699 with Temozolomide in metastatic melanoma.

      (xi) A phase II trial of Symadex (C-1311) in third line metastatic colorectal cancer.

      (xii) A first in human phase I trial of NC-6004 (Nanoplatin) in patients with advanced solid tumours.

      (xiii) A Cancer Research UK phase I trial to evaluate the safety,tolerability and pharmacokinetics of 17-dimethylaminoethyl-amino-17-demethoxygeldanamycin given as a once weekly infusion in patients with advanced solid tumours.

      (xiv) Horizon 2: a randomised phase III study of Cediranib or placebo with Capecitabine and Oxaliplatin in patients with previously untreated metastatic colorectal cancer.

      (xv) ACTIVPAL: A feasibility study of physical activity level as an outcome measure for use in cancer cachexia trials.

      (xvi) Randomized phase II study to assess the efficacy and safety of ZD6474 in combination with FOLFIRI versus FOLFIRI alone for the treatment of colorectal cancer in patients who have failed therapy with an oxaliplatin and fluoropyrimidine containing regimen (UK Chief Investigator).

      (xvii) Randomised phase II placebo-controlled study of transdermal AGI 004 for the control of chemotherapy-induced diarrhoea (global Chief Investigator).

      (xviii) DACROC: A Cancer Research UK randomised phase II trial of the DNA hypomethylating agent Decitabine given intravenously in combination with Carboplatin versus Carboplatin alone in patients with progressive, advanced ovarian cancer.

      (xix) COIN: a phase III trial comparing continuous chemotherapy plus cetuximab, intermittent chemotherapy and standard continuous palliative combination chemotherapy with oxaliplatin and a fluoropyrimidine in the first line treatment of metastatic colorectal cancer (one of four national co-investigators).

      (xx) A phase I study to determine the safety, pharmacokinetics, and

      pharmacodynamics of GSK461364, a Polo-like Kinase 1 (PLK1) inhibitor, in adults with advanced solid tumors or Non-Hodgkin's Lymphoma.

      (xxi) QUASAR 2: a multicentre international study of capecitabine with or without bevacizumab as adjuvant treatment of colorectal cancer.

      (xxii) FOLFERA: Randomised phase II trial of FOLFIRI +/- zibotentan in second-line metastatic colorectal cancer.

      (xxiii) ASPECCT: A randomised phase III study of Panitumumab versus Cetuximab in KRAS wild-type third-line metastatic colorectal cancer.

      (xxiv) GAIN-C: A randomised phase II study of RO5083945 with FOLFIRI versus FOLFIRI plus Cetuximab or FOLFIRI alone in second-line metastatic colorectal cancer.

      (xxv) FOLFERA: a randomised phase II study of Irinotecan, 5-Fluorouracil and Folinic Acid with or without the addition of an endothelin receptor antagonist in patients with metastatic colorectal cancer after failure of Oxaliplatin-containing chemotherapy.

      (xxvi) A phase I study of the PARP inhibitor PF-01367338 in combination with several chemotherapeutic regimens in adult patients with advanced solid tumours.

      (xxvii) SCOT: Short Course Oncology Therapy study of adjuvant chemotherapy in colorectal cancer.  

      (xxviii) A Phase I Open-label, Dose Escalation Study of S-222611 in Patients with Solid Tumours.    

      (xxix) I was local PI and one of three national co-investigators on the NCRI national COIN-B trial, with Dr Harpreet Wassan as Chief Investigator. This was a two-arm randomised phase II trial of intermittent chemotherapy with continuous cetuximab and of intermittent chemotherapy with intermittent cetuximab in the first line treatment of metastatic colorectal cancer.

      (xxx) I was local PI and one of the national co-investigators on the NCRI national FOCUS 3 trial, with Prof Tim Maughan as Chief Investigator. This was a randomised phase II trial to determine the feasibility of molecular selection of first-line therapy in patients with metastatic colorectal cancer.

      (xxxi) A phase I/II trial of the oral MEK inhibitor WX-554.         

      11. I was local AI on the following trials in NICCTU/NICTN, now closed:

      (i) Victor: A phase III randomised double-blind, placebo controlled study of Vioxx in colorectal cancer patients following potentially curative therapy.

      (ii) A prospective evaluation of CT portography, MRI and PET in the detection and quantification of hepatic colorectal metastases.

      (iii) EPOC - An EORTC study on peri-operative chemotherapy with FOLFOX4 versus surgery alone in resectable colorectal liver metastases.

      (iv) A pharmacokinetic study on Monocyte Esterase deficiency and Irinotecan activation .

      (v) A phase II study of Taxoprexin in patients with metastatic gastric or oesophageal adenocarcinoma.

      (vi) Eltax: A phase I and pharmacokinetic study of weekly Docetaxel and Oxaliplatin in patients with advanced solid tumours.               

      (vii) Gem-Cis: An extended phase II feasibility study of Gemcitabine and Cisplatin in advanced oesophageal cancer.

      (viii) A phase II study of Capecitabine and Oxaliplatin combination chemotherapy in patients with inoperable adenocarcinoma of the gallbladder or biliary tract.

      (ix) ACT II: A phase III trial of chemoradiation and maintenance therapy for patients with anal cancer.

      (x) Taxium: a phase I study of combined Docetaxel and repeated Rhenium-186 HEDP in hormone refractory prostate cancer metastatic to bone.

      (xi) VECarboX: a phase I study of Bortezomib in addition to Epirubicin, Carboplatin and Capecitabine in advanced gastric and gastro-oesophageal junction adenocarcinoma.

      (xii) New EPOC: A phase III RCT of combination chemotherapy with and without cetuximab pre and post operatively in patients with resectable colorectal liver metastases.

      (xiii) A study of carfilzomib in patients with varying levels of hepatic dysfunction.

      12. During my appointment in NCI, I also gained experience in the use of the following investigational agents/therapies in clinical trials: histone deacetylase inhibitors, angiogenesis inhibitors, cell cycle/kinase/cdk inhibitors, p-glcoprotein inhibitors, Her2 inhibitors, immunotoxins, matrix metalloprotease inhibitors, DNA helicase inhibitors, cancer vaccines, and experimental autologous and non-myeloablative allogeneic transplants with T cell manipulation.

      13. I was study co-ordinator/AI for a NCI first in human phase I trial of the HSP90 inhibitor 17-AAG (17-allyaminogeldanamycin) in humans with solid tumours. This novel compound inhibits heat shock protein 90. I was also involved with pharmacokinetic and translational pharmacodynamic analysis of this compound.

      14. As a member of both the NCI Developmental Therapeutics Department and the Gastrointestinal Oncology Team, I was also AI in the following phase I trials:

      (a) capecitabine and oxaliplatin in GI cancer,

      (b) oxaliplatin in patients with solid tumours and renal or hepatic impairment,

      (c) oral 5-fluorouracil, leucovorin and eniluracil in solid tumours,

      (d) infusional 5-fluorouracil and gemcitabine in solid tumours.

      15. In NCI, I developed with colleagues a HPLC assay for vinorelbine to study the pharmacokinetics of this agent in combination with the third generation p-glycoprotein pump inhibitor XR9576 in a phase I clinical trial. The assay involves a novel solid-phase extraction method from plasma and fluorescence detection. I also recruited and treated patients on this trial.

      16. I was the study co-ordinator/AI of the N. Ireland adjuvant colorectal cancer trial between 1994-2001 and the PI on the study since 2001. The trial commenced enrolment in 1994, closed in 1997 and is about to be submitted for publication.

      Frequent Journals

      • British Journal of Cancer

        ISSNs: 0007-0920, 1532-1827

        Additional searchable ISSN (Electronic): 1532-1827

        Nature Publishing Group

        Scopus rating (2016): SJR 2.924 SNIP 1.775

        Journal

      • Clinical Cancer Research

        ISSNs: 1078-0432

        Additional searchable ISSN (Electronic): 1557-3265, 1078-0432

        AMER ASSOC CANCER RESEARCH

        Scopus rating (2016): SJR 4.689 SNIP 1.983

        Journal

      • Journal of Clinical Oncology

        ISSNs: 0732-183X, 1527-7755

        Additional searchable ISSN (Electronic): 1527-7755

        AMER SOC CLINICAL ONCOLOGY

        Scopus rating (2016): SJR 8.883 SNIP 4.894

        Journal

      • Cancer Chemotherapy and Pharmacology

        ISSNs: 0344-5704

        Additional searchable ISSN (Electronic): 1432-0843

        Springer Verlag

        Scopus rating (2016): SJR 1.186 SNIP 0.919

        Journal

      • Lancet Oncology

        ISSNs: 1470-2045, 1474-5488

        Additional searchable ISSN (Electronic): 1474-5488

        Lancet Publishing Group

        Scopus rating (2016): SJR 13.39 SNIP 9.409

        Journal

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      Contribution to conference papers, events and activities

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