Dose Individualization of Pemetrexed - IMPROVE-III (IMPROVE-III)
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| ClinicalTrials.gov Identifier: NCT03655834 |
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Recruitment Status :
Recruiting
First Posted : August 31, 2018
Last Update Posted : March 1, 2019
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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:
- In patients with renal dysfunction, BSA-based dosing may lead to haematological toxicity
- Patients have to discontinue treatment due to declining renal function, and are withheld effective treatment
- 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 |
|---|---|---|
| Non Small Cell Lung Cancer Mesothelioma | Drug: Pemetrexed | Phase 4 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 10 participants |
| 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 : | February 1, 2019 |
| Estimated Primary Completion Date : | September 1, 2021 |
| Estimated Study Completion Date : | September 1, 2021 |
| Arm | Intervention/treatment |
|---|---|
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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
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Drug: Pemetrexed
patients will be administered a microdose with subsequent pharmacokinetic assessment.
Other Name: Microdosing |
- 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
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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)
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03655834
| Contact: Rob ter Heine, PhD | +31 (0)24 361 7744 | R.terHeine@radboudumc.nl | |
| Contact: Nikki de Rouw, MSc | +31 (0)24 361 7744 | R.terHeine@radboudmc.nl |
| Netherlands | |
| Jeroen Bosch Hospital | Not yet recruiting |
| 's-Hertogenbosch, Netherlands | |
| Contact: Bonne Biesma b.biesma@jbz.nl | |
| Principal Investigator: Bonne Biesma | |
| Sub-Investigator: Jeroen Derijks | |
| Antoni van Leeuwenhoek | Recruiting |
| Amsterdam, Netherlands | |
| Contact: Sjaak Burgers s.burgers@nki.nl | |
| Principal Investigator: Sjaak Burgers | |
| Sub-Investigator: Alwin Huitema | |
| Maastricht University Medical centre | Not yet recruiting |
| Maastricht, Netherlands | |
| Contact: Anne-Marie Dingemans a.dingemans@mumc.nl | |
| Principal Investigator: Anne-Marie Dingemans | |
| Radboud university medical centre | Not yet recruiting |
| Nijmegen, Netherlands | |
| Contact: Rob ter Heine R.terHeine@radboudumc.nl | |
| Principal Investigator: Rob ter Heine | |
| Sub-Investigator: Nikki de Rouw | |
| Sub-Investigator: Michel van den Heuvel | |
| Erasmus University Medical Centre | Not yet recruiting |
| Rotterdam, Netherlands | |
| Contact: Joachim Aerts j.aerts@erasmusmc.nl | |
| Principal Investigator: Joachim Aerts | |
| Sub-Investigator: Ron Mathijsen | |
| Principal Investigator: | Rob ter Heine, PhD | Radboud University |
| Responsible Party: | Radboud University |
| ClinicalTrials.gov Identifier: | NCT03655834 History of Changes |
| Other Study ID Numbers: |
IMPROVE-III |
| First Posted: | August 31, 2018 Key Record Dates |
| Last Update Posted: | March 1, 2019 |
| Last Verified: | January 2019 |
| Studies a U.S. FDA-regulated Drug Product: | No | |
| Studies a U.S. FDA-regulated Device Product: | No | |
Additional relevant MeSH terms:
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Lung Neoplasms Carcinoma, Non-Small-Cell Lung Mesothelioma Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms |
Adenoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms, Mesothelial Pemetrexed Antineoplastic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors |