ideasIdea
Replace fixed kidney and liver cut-offs with drug-specific, pharmacology-based thresholds
Most trials use the same blood-test cut-offs for kidney and liver function regardless of how the drug is cleared from the body. Setting the cut-off from the drug's own pharmacology would let many more people join safely.
Organ-function eligibility criteria (creatinine clearance, bilirubin, transaminases) would be set per drug from its clearance route and the results of early organ-impairment pharmacokinetic studies, rather than the default 'creatinine clearance above 60 ml/min' copied between protocols. Drugs with negligible renal clearance would have no renal cut-off; drugs with hepatic clearance would have a dose-adjusted cohort instead of an exclusion.
Hypothesis
Pharmacology-based thresholds will make at least 10-20 percent more patients eligible in older-skewed cancers without increasing dose-limiting toxicity, and will produce label dosing guidance for organ impairment at the time of approval rather than years later.
Rationale
Renal impairment is common in patients over 70 and in myeloma, bladder and kidney cancer; many modern agents (monoclonal antibodies, most ADCs) are not renally cleared, so the criterion excludes without protecting. The FDA organ-dysfunction eligibility guidance supports this approach.
What would test it
A sponsor applies PK-informed thresholds across its oncology portfolio for two years and reports the eligible fraction, DLT rates and organ-impairment sub-cohort outcomes versus its historical protocols.
Maturity
speculative
Who has to act
industry
Cost to try
Small (under $1M)
Years to first evidence
3
Bottlenecks it attacks
- Trials enrol too few, too slowly · Fewer than one in ten adults with cancer joins a trial. Trials close for lack of patients, not lack of ideas.
- Wrong doses · Most drug doses were chosen as the highest a person can tolerate, which is often more than they need.
- Older and multimorbid patients are excluded and undertreated · Most people with cancer are over 65 but most trial patients are younger and fitter. We guess how to treat the majority.