Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE4
6 participants
INTERVENTIONAL
2019-02-01
2023-12-29
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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 these 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
Objective:
The main objective is to develop a safe dosing regimen for pemetrexed in patients with renal impairment.
Study design:
IMPROVE-I is a single arm dose finding study to assess the feasibility of renal function-based dosing of pemetrexed in combination with folinic acid or folinic acid and pegfilgrastim in renally impaired patients.
Study population:
IMPROVE-I includes a maximum of twelve evaluable patients with NSCLC or mesothelioma with a renal function \<45ml/min that meet all other requirements for pemetrexed treatment.
Intervention:
IMPROVE-I: patients who have an indication for treatment with pemetrexed, but who have an impaired renal function will be treated with pemetrexed in combination with folinic acid rescue therapy. Dosing of pemetrexed will be based on renal function to reach the target AUC. As a safety measure a minimum of 4 intra-patient dose escalations in the first patient will be performed starting from 10% of the target AUC. A standard 3+3 study design is used. If folinic acid is not sufficient to prevent haematotoxicity, prophylactic treatment with pegfilgrastim will be added to the combination therapy.
Main study endpoints:
IMPROVE-I: The fraction of patients safely reaching the target dose.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
We consider the extra burden from participating in the planned studies limited. The extra interventions compared to routine care, consist of sampling extra blood. The pharmacokinetic assessments require placement of one additional intravenous catheter. To ensure minimal impact of study participation on daily life, we will use a limited sampling strategy. Patients may benefit from participating in IMPROVE I, as they will be treated with a potentially safe and effective drug that is dosed individually, which prevents toxic exposure.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Impaired renal function
patients will be treated with pemetrexed, with dosing based on renal function in combination with oral folinic acid rescue
Pemetrexed + oral folinic acid rescue
3+3 dose escalation study of pemetrexed in patients with impaired renal function in combination with roal folinic acid rescue
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Pemetrexed + oral folinic acid rescue
3+3 dose escalation study of pemetrexed in patients with impaired renal function in combination with roal folinic acid rescue
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Eligible for treatment with pemetrexed-based chemotherapy based on indication
3. Estimated creatinine clearance \<45ml/min
4. Eastern Cooperative Oncology Group (ECOG) performance score of 0-2
5. Subject is able and willing to sign the Informed Consent Form
Exclusion Criteria
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)
1. Hypersensitivity to the active substance or to any of the excipients
2. Pregnancy or lactation
3. Concomitant yellow fever vaccine
3. The presence of clinically relevant pharmacokinetic interactions, according to the current SmPC
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
ZonMw: The Netherlands Organisation for Health Research and Development
OTHER
Radboud University Medical Center
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Rob ter Heine, PhD
Role: PRINCIPAL_INVESTIGATOR
Radboud University Medical Center
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Jeroen Bosch Hospital
's-Hertogenbosch, , Netherlands
Antoni van Leeuwenhoek
Amsterdam, , Netherlands
Catharina hospital
Eindhoven, , Netherlands
Maastricht University Medical centre
Maastricht, , Netherlands
Radboud university medical centre
Nijmegen, , Netherlands
Erasmus University Medical Centre
Rotterdam, , Netherlands
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
de Rouw N, de Boer M, Boosman RJ, van den Heuvel MM, Burger DM, Lieverse JE, Derijks HJ, Frederix GWJ, Ter Heine R. The Pharmacoeconomic Benefits of Pemetrexed Dose Individualization in Patients With Lung Cancer. Clin Pharmacol Ther. 2022 May;111(5):1103-1110. doi: 10.1002/cpt.2529. Epub 2022 Feb 21.
Boosman RJ, Dorlo TPC, de Rouw N, Burgers JA, Dingemans AC, van den Heuvel MM, Hendriks LEL, Biesma B, Aerts JGJV, Croes S, Mathijssen RHJ, Huitema ADR, Ter Heine R. Toxicity of pemetrexed during renal impairment explained-Implications for safe treatment. Int J Cancer. 2021 Oct 15;149(8):1576-1584. doi: 10.1002/ijc.33721. Epub 2021 Jul 7.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
IMPROVE-I
Identifier Type: -
Identifier Source: org_study_id