Dose Individualization of Pemetrexed - IMPROVE-III
Status:
Recruiting
Trial end date:
2021-12-01
Target enrollment:
Participant gender:
Summary
Rationale:
Pemetrexed is a multi-targeted folate antagonist, which is primarily indicated for the
treatment of advanced non-small cell lung cancer (NSCLC) and mesothelioma. Dosing of
cytotoxic agents like pemetrexed requires balancing the dual risk of sub-therapy and
toxicity. Administration of pemetrexed to patients with a creatinine clearance <45 ml/min is
currently not advised. Pemetrexed is dosed based on body surface area (BSA), while renal
function and dose are the sole determinants for systemic exposure. This causes 3 major
issues:
1. In patients with renal dysfunction, BSA-based dosing may lead to haematological toxicity
2. Patients have to discontinue treatment due to declining renal function, and are withheld
effective treatment
3. Even in patients with adequate renal function (GFR >45 ml/min) treatment may be improved
by individualized dosing based on renal function, resulting in less toxicity. Also,
BSA-based dosing may lead to ineffective therapy in patients with above average renal
function.
The investigators aim to address these problems.
Objective: The overall main objective is to develop a safe and effective individualized
dosing regimen for pemetrexed.
Study design: IMPROVE-III is an explorative microdosing study to assess the extrapolability
of microdose-pharmacokinetics to the pharmacokinetics of a therapeutic dose.
Study population: IMPROVE-III includes 10 patients of IMPROVE-I and/or IMPROVE-II.
Intervention: patients will be administered a microdose with subsequent pharmacokinetic
assessment.
Main study endpoints: The predictive performance of microdosing to predict full dose
pharmacokinetics
Phase:
Phase 4
Details
Lead Sponsor:
Radboud University
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development