Metals in Medicine Consortium Sydney Cancer Centre

1. Metals in Medicine Consortium Sydney Cancer Centre

2. Sydney Cancer Centre • Clinical Oncology Departments of: • Royal Prince Alfred Hospital • Medical Oncology • Radiation Oncology • Surgical Units (urology, melanoma, breast, GI, H&N, cardiothoracic, etc) • Palliative Care • Haematology • Concord Hospital • Dubbo Hospital

3. SCC Clinical Research Links • Pharmaceutical Industry • University of Sydney (Med Psychology, Chemistry, Pharmacology) • Australian cooperative groups (disease specific) • US National Cancer Institute: • US cooperative groups (ph III) • Cornell University phase II consortium (ph II) • CTEP organ dysfunction working group (ph I) • Other international cooperative groups

4. Essential Clinical Resources for Developmental Therapeutics Research • Clinicians • Patients • Clinical research staff • Regulatory infrastructure • Laboratory interface

5. SCC Clinical Capability (Medical Oncology) A/Prof Michael Boyer Dr Lisa Horvath Dr Philip Beale Prof John Simes Dr Jane Beith Dr Martin Stockler A/Prof Stephen Clarke Dr Anne Sullivan Dr Anne Hamilton Prof Martin Tattersall • 2000 new patients per year • 200 patients on clinical trials per year • 40 active protocols at any point in time • 12 research staff (nurses / admin) including • RT / Concord / Dubbo

6. Key SCC Personnel - Metals in Medicine • Dr Philip Beale • Director, Med Oncology, CGRH/Dubbo • GI, gynae, breast, clin pharm • A/Prof Michael Boyer • Director, Med Oncology, CSAHS/RPAH • lung, GU, H&N • A/Prof Stephen Clarke • Head, Clinical Pharmacology • GI, lung, clin pharm • Dr Anne Hamilton • Head, Clinical Trials • breast, melanoma, gynae, clin pharm

7. End-points of Phase I studies • Recommended phase II dose and schedule • Human toxicology profile • Pharmacokinetics • Pharmacodynamics • Preliminary efficacy data

8. Role of Clinicians in Developmental Therapeutics Research • Protocol Planning (Registration Strategy) • Patient Selection and Treatment • Translational Laboratory Research Capability (“Bench to Bedside”) • Imaging Capability

9. Protocol Planning (Registration strategy) • selection of schedule / route of administration • selection of starting dose / dose escalation plan • selection of monitoring according to knowledge of toxicities in drugs of same class / preclinical data • development of strategies for managing side effects / problems as they occur • identification of clinical “niches” for drug development • knowledge of competing molecules

10. Patient Selection and Treatment • identification of appropriate patients • informed consent • drug administration • monitoring and management of efficacy and toxicity • determination of relationship of clinical events to the study drug • supportive care • reporting (regulatory)

11. Translational Research Capability“Bench to Bedside” • Concord Laboratory • Cell lines • In vitro drug activity in sensitive and resistant cell lines • Animal (xenografts / immune competent animals) • pharmacokinetics (LCMS) • pharmacodynamics • toxicology • anti-tumour activity

12. Translational Research Capability“Bench to Bedside” • Human (pretreated cancer / tumour targeted population) • pharmacokinetics (LCMS) • pharmacodynamics • PET labelled compounds (tissue distribution / “real time” PK)