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

therapeutics. Proposed exploratory INDs
may start by obtaining PK data suggesting
that appropriate drug levels in plasma
and tumor can be achieved. Next, PD
studies exploring how the agent affects
its proposed target in vivo would be
appropriate.
Exploratory IND studies embody the ideal
drug development scenario required
to conduct a limited, single-dose PK/PD
dose-escalation study in humans. In such
trials, researchers perform real-time PK/PD
studies to guide dose escalation instead of
escalation to maximum tolerated dose
98 ■ P R O G R A M A C C O M P L I S H M E N T S 2 0 0 6
as is now the norm in phase I trials. This
approach is essential for patient safety
in early human clinical trials.
The distinctive features of phase 0
studies are:
■ First-in-human, with single or combination
drugs
■ Molecules from CCR, academia, small
biotech
■ Small patient numbers (6–10); joint
CCR-DCTD clinical trial effort performed
in the Clinical Research Center
■ Provide PK/PD data to support rapid
future dose escalation based on extensive
preclinical toxicology and target
effect studies
■ Initial target assay development and
drug/target assessments (primary
and surrogate, imaging and molecular
expression)
■ Preliminary toxicity evaluation in
humans
■ Inform subsequent broad phase I/II trials
■ High throughput of trials, each
completed in three to six months
Joint Development Committee
A joint development committee (JDC)
has been created by DCTD and CCR to
coordinate the joint early therapeutics
development program and the exploratory
IND efforts. This committee is
charged with determining overall project
priorities, allocating resources, and providing
product development teams with
guidance and feedback monthly.