Metals in Medicine Consortium

Sydney Cancer Centre

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

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

Essential Clinical Resources for Developmental Therapeutics Research

• Clinicians

• Patients

• Clinical research staff

• Regulatory infrastructure

• Laboratory interface

SCC Clinical Capability (Medical Oncology)

A/Prof Michael Boyer Dr Lisa Horvath Dr Philip Beale Prof John Simes Dr Jane Beith Dr Martin StocklerA/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

Key SCC Personnel - Metals in Medicine

• Dr Philip BealeDirector, Med Oncology, CGRH/Dubbo

GI, gynae, breast, clin pharm

• A/Prof Michael BoyerDirector, Med Oncology, CSAHS/RPAH

lung, GU, H&N

• A/Prof Stephen ClarkeHead, Clinical Pharmacology

GI, lung, clin pharm

• Dr Anne HamiltonHead, Clinical Trials

breast, melanoma, gynae, clin pharm

End-points of Phase I studies

• Recommended phase II dose and schedule• Human toxicology profile• Pharmacokinetics• Pharmacodynamics• Preliminary efficacy data

Role of Clinicians in Developmental Therapeutics Research

1. Protocol Planning (Registration Strategy)

2. Patient Selection and Treatment

3. Translational Laboratory Research Capability (“Bench to Bedside”)

4. Imaging Capability

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

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)

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

Translational Research Capability“Bench to Bedside”

Human (pretreated cancer / tumour targeted population)

• pharmacokinetics (LCMS)• pharmacodynamics

• PET labelled compounds (tissue distribution / “real time” PK)