Eligibility of patients with renal impairment for Phase I trials: Time for a rethink?

Area of Science:

• Oncology
• Pharmacology
• Nephrology

Background:

• Historically, patients with renal dysfunction have been excluded from Phase I cancer clinical trials.
• Limited pharmacokinetic and pharmacodynamic data exist for cancer drugs in patients with renal impairment.
• No formal studies are typically conducted to assess drug behavior in this population.

Purpose of the Study:

• To discuss the potential inclusion of patients with asymptomatic mild to moderate renal impairment in selected Phase I trials.
• To highlight the benefits of generating timely data on new cancer agents in this specific patient group.
• To advocate for increased patient access to experimental cancer therapies.

Main Methods:

• This paper presents a discussion and recommendation based on existing clinical challenges and trial design considerations.
• It reviews the rationale for including patients with asymptomatic mild to moderate renal dysfunction in early-phase studies.
• It emphasizes the need for careful selection of appropriate trials.

Main Results:

• The inclusion of patients with asymptomatic mild to moderate renal dysfunction in selected Phase I trials is feasible.
• This approach can yield valuable pharmacokinetic and pharmacodynamic data for new cancer drugs.
• It offers a pathway to expand access to novel treatments for a frequently excluded patient population.

Conclusions:

• Patients with asymptomatic mild to moderate renal impairment can be appropriately enrolled in select Phase I cancer trials.
• This strategy addresses a critical data gap and enhances patient access to investigational cancer therapies.
• Further research and guideline development are warranted to facilitate this inclusion.