The PMH Phase I Consortium, led by Dr. Lillian Siu, is a part of the Robert and Maggie Bras and Family Drug Development Program (DDP) at PMH, the largest new drug development program in Canada and the only centre outside the US to have a contract with the NIH for Early Phase Therapeutic studies. PMH and its research arm Ontario Cancer Institute (OCI), both as part of the University Health Network (UHN), have achieved an international reputation as a global leader in the fight against cancer. The goals of PMH Phase I Consortium include: 1) To design and implement early phase studies that determine the safety and tolerability profiles, pharmacologic and molecular effects, as well as preliminary clinical efficacy of investigational anti-cancer agents;2) to provide appropriate patient populations access to I investigational anti-cancer agents via participation in clinical trials. The research and health care environment and the patient populations in our consortium are ideal for the conduct of phase I trials. The PMH Consortium has the patient referral base, experience, expertise, personnel, infrastructure, equipment I and facilities to conduct phase I single agent or combination trials, limited phase II trials and/or pilot trials of novel targeted agents. The PMH Phase I Consortium is committed to mount NCI-sponsored clinical trials as our top priority research effort. Our approach in the PMH Phase I Consortium for correlative laboratory studies to evaluate the pharmacokinetic, pharmacodynamic and pharmacogenomic endpoints in phase I trials of new agents, are illustrated using specific examples. The exact set of correlative studies to be performed with a novel agent will depend on the type of agent being evaluated, its molecular mechanism(s) of action, and existent knowledge. Relevance to public health: In phase I trials, new cancer treatments or combinations are tested on humans for the first time and they help determine how a drug should be given, how often it should be given, and how much is safe. Cancer is one of the leading causes of death and suffering worldwide and efforts at controlling and curing cancer continue to be needed. With the growing knowledge of molecular abnormalities that drive the cancer cell, and the emergence of new molecularly targeted agents, the ability to safely and efficiently evaluate these agents is crucial for advancing cancer care.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-SRRB-K (O1))
Program Officer
Ivy, S Percy
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University Health Network
Zip Code
M5 2-M9
Goncalves, Priscila H; Heilbrun, Lance K; Barrett, Michael T et al. (2017) A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma. Oncotarget 8:32918-32929
Chiu, Joanne W; Hotte, Sebastien J; Kollmannsberger, Christian K et al. (2016) A phase I trial of ANG1/2-Tie2 inhibitor trebaninib (AMG386) and temsirolimus in advanced solid tumors (PJC008/NCI?9041). Invest New Drugs 34:104-11
How, Jonathan; Minden, Mark D; Brian, Leber et al. (2015) A phase I trial of two sequence-specific schedules of decitabine and vorinostat in patients with acute myeloid leukemia. Leuk Lymphoma 56:2793-802
Reiss, Kim A; Herman, Joseph M; Zahurak, Marianna et al. (2015) A Phase I study of veliparib (ABT-888) in combination with low-dose fractionated whole abdominal radiation therapy in patients with advanced solid malignancies and peritoneal carcinomatosis. Clin Cancer Res 21:68-76
LoConte, Noelle K; Razak, Albiruni R A; Ivy, Percy et al. (2015) A multicenter phase 1 study of ? -secretase inhibitor RO4929097 in combination with capecitabine in refractory solid tumors. Invest New Drugs 33:169-76
Richter, Suzanne; Bedard, Philippe L; Chen, Eric Xueyu et al. (2014) A phase I study of the oral gamma secretase inhibitor R04929097 in combination with gemcitabine in patients with advanced solid tumors (PHL-078/CTEP 8575). Invest New Drugs 32:243-9
Spreafico, Anna; Chi, Kim N; Sridhar, Srikala S et al. (2014) A randomized phase II study of cediranib alone versus cediranib in combination with dasatinib in docetaxel resistant, castration resistant prostate cancer patients. Invest New Drugs 32:1005-16
Abrams, Jeffrey S; Mooney, Margaret M; Zwiebel, James A et al. (2013) Implementation of timeline reforms speeds initiation of National Cancer Institute-sponsored trials. J Natl Cancer Inst 105:954-9
Sahebjam, S; Bedard, P L; Castonguay, V et al. (2013) A phase I study of the combination of ro4929097 and cediranib in patients with advanced solid tumours (PJC-004/NCI 8503). Br J Cancer 109:943-9
Diaz-Padilla, Ivan; Hirte, Hal; Oza, Amit M et al. (2013) A phase Ib combination study of RO4929097, a gamma-secretase inhibitor, and temsirolimus in patients with advanced solid tumors. Invest New Drugs 31:1182-91

Showing the most recent 10 out of 13 publications