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.