A Phase 4 interventional study of Pemetrexed in Non Small Cell Lung Cancer and Mesothelioma, sponsored by Radboud University Medical Center. Terminated at 5 sites in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-05-13.
Sponsored by Radboud University Medical Center · Phase 4, Interventional, and Treatment
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:
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-II is an open label, double arm, randomized study to compare renal function-based dosing of pemetrexed versus BSA-based dosing on attainment of therapeutic exposure.
Study population: IMPROVE-II includes 94 patients with NSCLC or mesothelioma that are eligible for pemetrexed treatment.
Intervention: patients will be randomized in a 1:1 ratio to Arm A (BSA-based dosing according drug label) or to Arm B (renal function based dosing). The renal function-based dose will be calculated to reach the target AUC. Pharmacokinetic assessment after administration will be performed after the first pemetrexed dose in both arms.
Main study endpoints: The fraction (percentage) of patients with attainment of therapeutic exposure with BSA-based dosing versus renal function-based dosing.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
The investigators 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, a limited sampling strategy will be used. Patients may benefit from participating in IMPROVE I and -II, as they will be treated with a potentially safe and effective drug that is dosed individually, which prevents toxic exposure.
7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.
This study's enrollment of 81 is above the median of 60 across 5,295 interventional studies indexed under Lung Neoplasms.
Browse Lung Neoplasms studies →Radboud University Medical Center is the lead sponsor of 959 studies on the registry; 134 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Contraindications for treatment with pemetrexed in line with the summary of product characteristics (SmPC) (except for creatinine clearance \<45 ml/min in IMPROVE-I)
Dosing of pemetrexed is based on BSA according drug label
Drug: Pemetrexed
Dosing of pemetrexed is based on renal function, calculated to reach the target AUC.
Drug: Pemetrexed
Dosing is either based on BSA or renal function
Exposure (AUC)
mg\*h/l
Time frame: 24 hours
The fraction (percentage) of patients with attainment of therapeutic exposure with BSA-based dosing versus renal function-based dosing.
The fraction (percentage) of patients with attainment of therapeutic exposure defined as an AUC of 164 mg\*h/l ±25%, with pemetrexed dosing based on renal function versus BSA-based dosing.
Time frame: 3 months
Population Clearance (Cl)
L/h
Time frame: 3 months
Population Intercompartmental Clearance (Q)
L/h
Time frame: 3 months
Population Central Volume of Distribution (V1)
L
Time frame: 24 hours
Population Peripheral Volume of Distribution (V2)
L
Time frame: 3 months
Performance of different renal function algorithms to predict pemetrexed
Significant change in objective function value (OFV) (\<3.84 with 1 degree of freedom)
Time frame: 3 months
Performance of different renal function algorithms to predict pemetrexed pharmacokinetics (decrease in variability)
Decrease in clearance variablity (%)
Time frame: 3 months
Hematologic assessment during dosing based on renal function in patients with a creatinine clearance >45ml/min versus dosing based on BSA.
Complete blood count (no per liter)
Time frame: 5 days
The incidence of hematologic dose limiting toxicities (DLT) and adverse events, as measured with the CTCAE V4'
through listing
Time frame: 3 months
The incidence of non-hematologic dose limiting toxicities (DLT) and adverse events, as measured with the CTCAE V4
through listing
Time frame: 3 months
The incidence of toxicity-related dose reductions, treatment delays and treatment discontinuation
through listing
Time frame: 3 months
Quality of life measured with the EORTC QLQ-C30/L13 questionnaire
0-100 scale
Time frame: 3 months
In silico evaluation of neutropenic response
Simulation of risk for neutropenic response
Time frame: 1 year
Neutropenia related costs
Euros
Time frame: 1 year
This study is terminated, as verified in May 2022. You cannot join it, but the record below documents what was studied.
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Radboud University Medical Center