National Cancer Institute - NCI Division of Cancer Treatment and ...

Joint Early Therapeutics
Development Program
The Division of Cancer Treatment and
Diagnosis (DCTD) is reexamining its
discovery and development paradigm.
Pharmacokinetic and pharmacodynamically
(PK/PD)–guided clinical trials are
being emphasized in conjunction with
assays of specific molecular targets. Such
studies are already used to examine the
biological effects of drugs in animals and
humans. By studying PK/PD responses,
researchers will be better able to administer
the appropriate dose to achieve
the desired therapeutic response with
a minimum risk of toxic effects.
A new collaborative effort between the
DTP drug developers in DCTD and the
programs and clinicians at the Center for
Cancer Research (CCR), called the joint
early therapeutics development program,
uses PK/PD principles to streamline the
development of novel cancer therapeutics.
This initiative builds on CCR’s strengths
in integrated research and its clinical
program, as well as DCTD’s expertise in
drug development and its relationships
with pharmaceutical companies. The
goal is to shorten the drug development
timeline for new molecular entities and
cytotoxic agents by rapidly screening
new drugs in humans before making a
commitment in time and resources to
a full therapeutic development plan.
In 2005, this new initiative began to take
shape. DTP’s Toxicology and Pharmacology
Branch identified laboratory resources
required to support the program and is
working to expand capacities to perform
PD assays, in vitro toxicity analysis, and
N E W I N I T I A T I V E S
virus toxicity testing. DTP also is augmenting
its animal model efficacy program. A
National Clinical Target Validation Laboratory
was established within the Toxicology
and Pharmacology Branch to assess the
pharmacodynamic effects of therapeutics
on cellular targets, perform target
validation assays, and evaluate the consequences
of anticancer drugs on patients
in early clinical trials.
Exploratory Investigational
New Drug Studies
The joint early therapeutics development
program will utilize a recent guidance
from the Food and Drug Administration
(FDA) concerning exploratory studies of
INDs. Exploratory IND studies, which are
also called phase 0 trials, will facilitate
targeted therapies being tested in patients
earlier in the drug development process.
This will allow informed decisions to proceed
or stop with that particular drug’s
development before expensive bulk drug
formulation and other steps such as additional
preclinical toxicology occur. New
advances in imaging technologies, which
can help detect whether an agent being
tested is reaching its target and producing
the desired effect, will also be employed.
A unique aspect of the program is that
extramural drug developers, for the first
time, will be offered opportunities to
utilize CCR resources for clinical trials
support. Candidate compounds for
exploratory IND studies may come
from intramural, extramural, academic
NCI-funded, or industry laboratories.
Consideration will be given to novel
small molecules, antibodies, or peptide
D E V E L O P M E N T A L T H E R A P E U T I C S P R O G R A M ■ 97