Clinical Trial Phases for Cytotoxic Therapies

Overview

In general clinical trials are grouped into four different clinical trial phases (Phase 1 through 4). They are listed at the end of this section in a table to help you compare them.

These phases have been in use for many years and were designed to evaluate new cytotoxic chemotherapy agents. These drugs affect all fast growing cells, not differentiating among them to act specifically on a single cell type and they are usually associated with significant side effects. With the advent of targeted therapies, new designs are being examined and are discussed later in this section.

 

Phase 1 Clinical Trials

Once a drug shows promise in translational studies using mice or other lab animals, it must be studied in humans to confirm that it is an effective and safe treatment.

Goal of phase 1: What dose is safe?

In the most common trial design, the very first three patients in the trial receive a starting dose that is less than the dose that begins to kill mice in the preclinical lab experiments. This starting dose is low to insure that study patients will be safe. If these patients do not experience toxicities then the next three patients will receive a higher dose of the drug.

The dose given continues to be increased by smaller percentages using groups of three people until one person experiences a toxicity. This is termed a dose-limiting toxicity (DLT), as this is the highest amount of the drug that patients can tolerate before experiencing side effects.

When one patient develops a DLT, three additional patients are treated with the drug at the same dose. If no other DLT is observed, dose escalation continues. If a second DLT develops in more than 33% of patients (2 out of 6) at a given dose level, dose escalation stops. Usually, the preceding dose level, a dose at which fewer than 33% of patients experienced a DLT, is recommended for further study in a Phase II evaluation.

How many people are enrolled?
15-30 in one or two centers

Risk vs. benefit?
For patients considering a clinical trial, a Phase 1 trial involves the most risk and the least likelihood of benefit. This is because these trials determine the initial safety data and the correct dose is determined. Most patients will not receive a dose high enough to be of benefit.

How long will the study take?
About two years

Summary: Phase I studies provide valuable information about the relationship between dose and toxicity but rarely about dose and anticancer effect (whether the dose kills cancer cells better than the standard treatment drug).