Dose Individualization of Pemetrexed - IMPROVE-III

Sponsor
Radboud University Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT03655834
Collaborator
ZonMw: The Netherlands Organisation for Health Research and Development (Other)
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Study Details

Study Description

Brief 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

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
10 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Diagnostic
Official Title:
Individualized Pemetrexed Dosing in Patients With Non-small Cell Lung Cancer or Mesothelioma Based on Renal Function to Improve Treatment Response
Actual Study Start Date :
Feb 1, 2019
Actual Primary Completion Date :
Sep 20, 2020
Actual Study Completion Date :
Aug 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Microdosing

Patients will be administered a microdose of pemetrexed with subsequent pharmacokinetic assessment. Afterwards the patients will continue in either IMPROVE-I or -II for second pharmacokinetic assessment

Drug: Pemetrexed
patients will be administered a microdose with subsequent pharmacokinetic assessment.
Other Names:
  • Microdosing
  • Outcome Measures

    Primary Outcome Measures

    1. The predictive performance of microdosing to predict full dose pharmacokinetics [3 months]

      Mean relative prediction error (MPE)

    2. The predictive performance of microdosing to predict full dose pharmacokinetics [3 months]

      Root mean squared relative prediction error (RMSE)

    3. Exposure (AUC) after microdose [1 day]

      mg*h/l

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. ≥18 years old

    2. Planned for treatment with pemetrexed-based chemotherapy in IMPROVE-I or -II.

    3. Eastern Cooperative Oncology Group (ECOG) performance score of 0-2

    4. Subject is able and willing to sign the Informed Consent Form

    Exclusion Criteria:
    1. Conditions that affect haemostasis in a way that blood drawing is complicated (to be assessed by physician)

    2. Contraindications for treatment with pemetrexed in line with the summary of product characteristics (SmPC) (except for creatinine clearance <45 ml/min in IMPROVE-I)

    3. Hypersensitivity to the active substance or to any of the excipients

    4. Pregnancy or lactation

    5. Concomitant yellow fever vaccine

    6. The presence of clinically relevant pharmacokinetic interactions, according to the current SmPC

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Jeroen Bosch Hospital 's-Hertogenbosch Netherlands
    2 Antoni van Leeuwenhoek Amsterdam Netherlands
    3 Maastricht University Medical centre Maastricht Netherlands
    4 Radboud university medical centre Nijmegen Netherlands
    5 Erasmus University Medical Centre Rotterdam Netherlands

    Sponsors and Collaborators

    • Radboud University Medical Center
    • ZonMw: The Netherlands Organisation for Health Research and Development

    Investigators

    • Principal Investigator: Rob ter Heine, PhD, Radboud University Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Radboud University Medical Center
    ClinicalTrials.gov Identifier:
    NCT03655834
    Other Study ID Numbers:
    • IMPROVE-III
    First Posted:
    Aug 31, 2018
    Last Update Posted:
    May 10, 2022
    Last Verified:
    May 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 10, 2022