Last Updated: 04/06/07
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 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 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
