Phase I Clinical Trials in Oncology

What Are the Steps in New Drug Development?

Preclinical phase

This includes discovering or creating a potential drug, formulating it for appropriate delivery, in vitro studies, and animal studies.

Traditional chemotherapy agents

In earlier times, the candidate drugs (chemotherapy agents) were identified from natural compounds and may have been subsequently chemically modified to enhance their properties. These were tested in cell culture systems or in animal models and then subsequently formulated for human studies.

”Targeted” agents

The steps in the development of “targeted agents are: Target identification → Creating appropriate compounds to attack the target by chemical or bioengineering (monoclonal antibodies) → Formulation/in vitro studies/in vivo studies in animal models.

Additional preclinical studies may include assays to identify the target inhibition in animal models and pharmacokinetic and pharmacodynamic studies to know the doses that are able to inhibit the target.

Preclinical studies will establish the following:

1. The pharmacokinetics of the agent

2. The efficacy of the agent in vitro and in animal models

3. The feasibility of creating a formulation of the candidate agent

4. The toxicity and the “lethal” dose in mammalian species. “Lethal dose” may not always be achieved in case of “targeted” agents. LD50 is defined as the dose which kills 50% of the animals – This was an important dose level which helped to identify a starting point for phase I trials, especially for phase I trials of traditional chemotherapy agents

5. Target inhibition and bioassays to demonstrate the same.

Clinical phase

Once a drug has completed preclinical efficacy and toxicity studies, the sponsor decides to proceed with trials in humans and starts with phase I studies and subsequently II, III, and IV studies. Phase 0 refers to a specific type of “clinical” trial and is not a preclinical phase of the drug development. Before starting the clinical trials in humans, the sponsor has to file an “Investigational New Drug (IND)” application with the drug controller.

The definition of “IND” as per the CDSCO is “new chemical or biological entity or a product having a therapeutic indication, but which has never been tested before on human participants.”

Publication History

Received: 09 January 2020

Accepted: 04 June 2020

Article published online:
14 May 2021