This guidance is one in a series of guidances that provide recommendations regarding eligibility criteria for clinical trials of investigational drugs or biological products for the treatment of cancer. Specifically, this guidance includes recommendations for sponsors and/or IRBs regarding the appropriate use of washout periods and concomitant medication exclusions.
Quick takeaways for sponsors:
Some eligibility criteria, such as specific washout periods and concomitant medication exclusions, have become default requirements in many protocols regardless of whether they are appropriate in a specific trial context. When these criteria are overly restrictive, it is more difficult to enroll subjects and the subjects that do ultimately enroll may not fully represent the population likely to use the drug in the “real world”.
What to consider when identifying an appropriate wash-out period:
- Consider the expected previous oncologic treatments and identify a wash-out period that reflects the pharmacokinetics (PK)/pharmacodynamics (PD) of those specific drugs.
- Time-based washout periods should be clearly justified in the protocol.
- Consider using laboratory test values rather than time-based washout periods when appropriate.
- Also, when appropriate, consider using a candidate’s recovery from previous treatments (ie, resolution of adverse events) as an alternative to a specific wash-out period.
What to do when identifying appropriate concomitant medication exclusions:
- Only exclude concomitant medications when there is a clear safety reason to do so such as known drug-drug interactions or potential for overlapping toxicities.
- Be prepared to adjust the exclusions as the drug development progresses and more information about the drug is known. Exclusions that are appropriate in a phase 1 study may be unnecessarily restrictive in a subsequent phase 3 study.
- If a concomitant medication is allowed but dosage adjustments are required for safety reasons, the protocol should include a rationale. Candidates should be informed of potential dosage changes.
The IRB perspective:
- The IRB will consider the recommendations included in this Guidance when reviewing cancer clinical trial protocol eligibility criteria.
- If appropriate the IRB may require that the consent form disclose any required concomitant medication dosage adjustments or exclusions.