Conducting clinical trials in cancer patients is inherently more challenging than other disease states because:

  • Preclinical strategies to evaluate novel oncology agents are suboptimal,
  • The number and type of prior treatments patients have undergone,
  • Novel agents are tested in patients with late-stage malignancies, which are inherently more difficult to treat than earlier malignancies.

More targeted and individualized therapy has presented exciting possibilities to combat disease, but the new approaches have also added complexity to clinical development.  Understanding the unique challenges and opportunities presented with phase 1 oncology trials is paramount for designing successful studies and keeping them on track.

Oncology trials are bound to enrolling patients with later-stage disease who have already been treated with standard of care. The reason for this distinctiveness is an ethical one; any new investigational agent bears the potential of failure or suboptimal therapeutic efficacy, and the inclusion of early stage patients who do have proven treatments would be regarded as unethical unless the new agent has shown activity.

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. 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. Even patients who meet all inclusion criteria for a study can have a rapid worsening of malignancy shortly after enrolling.

LEARN MORE.  If you want to learn more about: best practices for the development of a solid trial design; how technology-based tools such as EDC and clinical trial management can improve many aspects of the research process; and potential savings associated with selection of high-performing sites and personnel, please download a copy of our whitepaper entitled, “Ensuring Success in Early Phase Oncology Clinical Trials,” at

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