Completed

NCT Number: NCT03655834

Dose Individualization of Pemetrexed - IMPROVE-III

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

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Key information

Conditions

Non Small Cell Lung Cancer Adenoma Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Mesothelioma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Neoplasms, Mesothelial Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Jeroen Bosch Hospital, 's-Hertogenbosch, Netherlands

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

≥18 years old
Planned for treatment with pemetrexed-based chemotherapy in IMPROVE-I or -II.
Eastern Cooperative Oncology Group (ECOG) performance score of 0-2
Subject is able and willing to sign the Informed Consent Form

Exclusion criteria

Conditions that affect haemostasis in a way that blood drawing is complicated (to be assessed by physician)
Contraindications for treatment with pemetrexed in line with the summary of product characteristics (SmPC) (except for creatinine clearance <45 ml/min in IMPROVE-I)

Hypersensitivity to the active substance or to any of the excipients
Pregnancy or lactation
Concomitant yellow fever vaccine
The presence of clinically relevant pharmacokinetic interactions, according to the current SmPC

Treatment and study plan

Pemetrexed

Drug

patients will be administered a microdose with subsequent pharmacokinetic assessment.

Other names: Microdosing

Primary outcomes

The predictive performance of microdosing to predict full dose pharmacokinetics

Time frame: 3 months

Mean relative prediction error (MPE)
The predictive performance of microdosing to predict full dose pharmacokinetics

Time frame: 3 months

Root mean squared relative prediction error (RMSE)
Exposure (AUC) after microdose

Time frame: 1 day

mg*h/l

Sponsors and collaborators

Lead sponsor

Radboud University Medical Center

Other

Collaborators

ZonMw: The Netherlands Organisation for Health Research and Development

Registry information

Official study title

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

Acronym: IMPROVE-III

Important dates

Study start: 2019
Primary completion: 2020
Study completion: 2021
First posted: Aug 31, 2018
Registry last updated: May 10, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed