Folinic Acid for Prevention of Pemetrexed-induced Toxicity (FLEX)

August 17, 2023 updated by: Dr. N. (Nikki) de Rouw, Amphia Hospital

The Effect of Oral Folinic Acid Rescue Therapy on Pemetrexed Induced Neutropenia: A Randomized Open-label Trial

Objective The main objective is to evaluate the haematological toxicity in patients who use pemetrexed with and without rescue therapy with folinic acid.

Primary endpoint Difference between treatment groups in neutrophil count (*109/L) at day 8-10 after administration of pemetrexed (nadir).

Secondary endpoints The grade neutropenia (according to the CTCAE version 5, 2017) at day 8-10, the homocysteine plasma levels at baseline (predictor for developing toxicity), the efficacy of chemotherapy treatment based on response CT after cycle 2 and 4 and the incidence of discontinuation, dose delays and dose reductions of pemetrexed.

Trial design The FLEX-trial is a multi-centre, open label, double arm, randomized trial to compare neutropenia in patients with and without folinic acid rescue therapy where subjects are participating for 4 treatment cycles.

Population In total 50 patients (25 in each arm), >18 years with stage IV non-small cell lung cancer (NSCLC) or mesothelioma treated with pemetrexed (in combination with other chemo- or immunotherapy) are eligible for inclusion.

Interventions Follow-up will take place during the first 4 cycles of chemotherapy with pemetrexed. Patients in the intervention-arm will receive oral folinic acid orally 4 times 45mg / day for 3 days, starting 24 hours after the administration of pemetrexed.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Netherlands
    • Noord Brabant
      • Breda, Noord Brabant, Netherlands, 4817
        • Recruiting
        • Amphia Hospital
        • Contact:
        • Contact:
    • Zuid Holland
      • Dordrecht, Zuid Holland, Netherlands, 3318
        • Not yet recruiting
        • Albert Schweitzer Hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

  1. ≥18 years old
  2. Eligible for treatment with pemetrexed-based chemotherapy based on indication.
  3. ECOG performance score of 0-2.
  4. Subject is able and willing to sign the Informed Consent Form

A potential subject who meets any of the following criteria will be excluded from participation in this study:

  1. Contraindications for treatment with folinic acid in line with the SmPC.

    1. Hypersensitivity to the active substance or to any of the excipients.
    2. Anaemia caused by vitamin B12 deficiency.
  2. The presence of clinically relevant drug-drug interactions, according to the current SmPC of folinic acid.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Folinic acid arm
Patients in the intervention-arm will receive oral folinic acid orally 4 times 45mg / day for 3 days, starting 24 hours after the administration of pemetrexed.
Drug: Folinic acid
Follow-up will take place during the first 4 cycles of chemotherapy with pemetrexed. Patients in the intervention-arm will receive oral folinic acid orally 4 times 45mg / day for 3 days, starting 24 hours after the administration of pemetrexed.
No Intervention: No folinic acid arm
Patients will be treated according to regular care.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Difference in neutrophil count (*109/L) at day 8-10 after pemetrexed administration during 2 cycles of chemotherapy
Time Frame: Between day 8-10 in the first 2 cycles (each cycle is 21 days)
To evaluate the haematological toxicity (continuous measure) in patients who use pemetrexed with and without rescue therapy with folinic acid.
Between day 8-10 in the first 2 cycles (each cycle is 21 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Grade neutropenia (according to the CTCAE version 5, 2017) at day 8-10 after pemetrexed administration during 2 cycles of chemotherapy
Time Frame: Between day 8-10 in the first 2 cycles (each cycle is 21 days)
To evaluate the difference in haematological toxicity based on the CTCAE criteria for neutrophil count
Between day 8-10 in the first 2 cycles (each cycle is 21 days)
Homocysteine plasma levels at baseline (μmol/L)
Time Frame: Once, before the start of the first cycle (each cycle is 21 days)
To evaluate the influence of baseline homocysteine plasma levels on occurrence of haematological toxicity.
Once, before the start of the first cycle (each cycle is 21 days)
Efficacy based on response CT after cycle 2 and 4 (categorical: response, partial response, progression)
Time Frame: After the second and fourth cycle (each cycle is 21 days)
To evaluate the efficacy of the treatment with pemetrexed (based on CT-scan).
After the second and fourth cycle (each cycle is 21 days)
Incidence of discontinuation, dose delays and dose reductions of pemetrexed
Time Frame: 3 months
To evaluate the incidence of treatment delay or dose reduction of pemetrexed.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Amphia Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Albert Schweitzer Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 6, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 26, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 17, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 24, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 24, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 17, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1891

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on NSCLC

Clinical Trials on Folinic acid

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings