Non Small Cell Lung CancerPhase 4IMPROVE-IIINCT03655834
Dose Individualization of Pemetrexed - IMPROVE-III
A Phase 4 study testing Pemetrexed in people with Non Small Cell Lung Cancer and Mesothelioma, run by Radboud University Medical Center at 5 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer, Mesothelioma
- What is being tested?
- Pemetrexed
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 5 sitesNetherlands
- Study dates
- 1 Feb 2019to 1 Aug 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Netherlands5 sites
Jeroen Bosch Hospital
's-Hertogenbosch
Antoni van Leeuwenhoek
Amsterdam
Maastricht University Medical centre
Maastricht
Radboud university medical centre
Nijmegen
Erasmus University Medical Centre
Rotterdam
About this study
Official title: Individualized Pemetrexed Dosing in Patients With Non-small Cell Lung Cancer or Mesothelioma Based on Renal Function to Improve Treatment Response
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:
Read more
- 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
- Conditions
- Non Small Cell Lung Cancer, Mesothelioma
- Being tested
- Pemetrexed
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Mesothelioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PemetrexedDrug
Also called Microdosing
patients will be administered a microdose with subsequent pharmacokinetic assessment.
| Study group | Role | What they receive |
|---|---|---|
| Microdosing | Experimental | 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 Receives: Drug: Pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
The predictive performance of microdosing to predict full dose pharmacokinetics
Mean relative prediction error (MPE)
Measured: 3 months
The predictive performance of microdosing to predict full dose pharmacokinetics
Root mean squared relative prediction error (RMSE)
Measured: 3 months
Exposure (AUC) after microdose
mg*h/l
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2018
- Study start1 Feb 2019
- Primary completion20 Sep 2020
- Study completion1 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Sponsor
- Investigators
- Rob ter Heine, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03655834
- Sponsor's protocol ID
- IMPROVE-III
- Acronym
- IMPROVE-III
- Status last verified
- May 2022
- First submitted
- 14 May 2018
- Last updated
- 10 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Boosman RJ, de Rouw N, Huitema ADR, Burgers JA, Ter Heine R. Prediction of the pharmacokinetics of pemetrexed with a low test dose: A proof-of-concept study. Br J Clin Pharmacol. 2023 Feb;89(2):699-704. doi: 10.1111/bcp.15520. Epub 2022 Sep 21.
PubMed 36053283
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Individualized Pemetrexed Dosing in Patients With Non-small Cell Lung Cancer or Mesothelioma Based on Renal Function to Improve Treatment Response
- ClinicalTrials.gov ID
- NCT03655834
- Acronym / sponsor ID
- IMPROVE-III / IMPROVE-III
- Conditions
- Non Small Cell Lung Cancer, Mesothelioma
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- 1 Feb 2019 (actual)
- Primary completion
- 20 Sep 2020 (actual)
- Study completion
- 1 Aug 2021 (actual)
- First posted
- 31 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Microdosing | Experimental | Drug: PemetrexedPatients 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- ≥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
Key exclusion criteria (6 listed)
- 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)
- The presence of clinically relevant pharmacokinetic interactions, according to the current SmPC
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PemetrexedAlso: Microdosingpatients will be administered a microdose with subsequent pharmacokinetic assessment. | Drug | Microdosing |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2022.
- Derived from this study: PubMed 36053283Boosman RJ, de Rouw N, Huitema ADR, Burgers JA, Ter Heine R. Prediction of the pharmacokinetics of pemetrexed with a low test dose: A proof-of-concept study. Br J Clin Pharmacol. 2023 Feb;89(2):699-704. doi: 10.1111/bcp.15520. Epub 2022 Sep 21.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rob ter Heine, PhD principal investigator
Radboud University Medical Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pemetrexed in people with Non Small Cell Lung Cancer and Mesothelioma, run by Radboud University Medical Center at 5 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The predictive performance of microdosing to predict full dose pharmacokinetics (time frame: 3 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03655834, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2022.