Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs

Chapter 60

Phase I Trials in Oncology

Anastasia Ivanova

60.1 Introduction

According to ClinicalTrials.gov, an official clinical trial resource of the National Institutes of Health, phase I clinical trials are initial studies with volunteers or patients to determine the metabolism and pharmacologic actions of drugs in humans, to assess the side effects associated with increasing doses, and to gain early evidence of effectiveness or efficacy. Conducting phase I oncology trials with healthy volunteers would potentially expose them to severe toxicity events. Therefore, phase I trials in oncology are usually conducted with patients, often patients for whom other options do not exist. The goals of phase I trials in oncology are [1] to estimate the maximum tolerable dose of the investigational agent, [2] to determine dose-limiting toxicities, and [3] in many cases, to also investigate the pharmacokinetics and pharmacodynamics of the investigational drug.

Most of the existing oncology therapies are cytotoxic. The word cytotoxic means toxic to cells, or cell-killing. Chemotherapy and radiotherapy are the examples of cytotoxic therapies widely used in oncology. A new class of cancer drugs acting as cytostatic agents is being developed. These agents usually target one specific process involved in malignant transformation of cells, and they result in growth inhibition rather than tumor regression. Based on their specific mechanism of action, these target-specific agents are expected to have ...