NCT03655834

Dose Individualization of Pemetrexed - IMPROVE-III

Individualized Pemetrexed Dosing in Patients With Non-small Cell Lung Cancer or Mesothelioma Based on Renal Function to Improve Treatment Response

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: Radboud University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Conditions

• Non Small Cell Lung Cancer
• Mesothelioma

Interventions

Type	Name	Description
DRUG	Pemetrexed	patients will be administered a microdose with subsequent pharmacokinetic assessment.

Timeline

• Start date: 2019-02-01
• Primary completion: 2020-09-20
• Completion: 2021-08-01
• First posted: 2018-08-31
• Last updated: 2022-05-10

Locations

5 sites across 1 country: Netherlands