Ensuring Success in Early Phase Oncology Clinical Trials | Page 2

Late-stage patients tend to be less responsive to medications, and they tend to be more confounded by co-morbities or potential for interaction with other drugs. Their response to an investigational therapy may not represent the response in early stage disease. This is a particular concern for immunological treatment approaches like tumor vaccines, in which the patient’s immune system defends against the tumor, because in late stage disease, the immune system is less able to mount a response. In patients with late-stage disease, it can be difficult to discern whether adverse events are caused by the investigational agent, some other anti-cancer agent being taken as standard of care, or by the disease itself. The main benefit of conducting trials in patients with disease is that efficacy data may be obtained. However, gathering meaningful data can be difficult and take a long time. For many non-oncology indications, such as high blood pressure or diabetes, objective results can be seen within days to weeks. Evaluating meaningful clinical efficacy in patients with tumors takes months to years. Although tumor responses can sometimes be evaluated after a short time of 1 to 3 months, endpoints like disease-free survival or time to progression can only be learned if patients are followed beyond the median time to progression of their tumor, which can easily reach 1 year or longer. Given the time enrollment takes, a Phase 1 oncology trial can take 1.5 to 2 years. Enrollment times can be especially long because oncology trials usually need to be conducted over a number of dose escalation levels before any anti-tumor efficacy can be identified. Before a trial is conducted, careful consideration needs to be given to whether and how a drug might be beneficial or harmful to patients. Early phase oncology trials enroll patients who have been dealing with disease for a long time and are facing a difficult prognosis. “Patients can get really sick really fast,” according to Catherine Holloway, MS, global project director at Clinipace Worldwide. Even patients who meet all inclusion criteria for a study can have a rapid worsening of malignancy shortly after enrolling. Having patients get very sick or die during a trial takes an emotional toll on all members of the study team. In general, oncology patients are committed to supporting progress in science and medicine. Therefore, patients tend to be compliant with the treatment regimen and evaluations.