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

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • 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 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

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
Intervention / Treatment
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

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

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

Amphia Hospital

Collaborators

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)

February 6, 2023

Primary Completion (Estimated)

January 1, 2024

Study Completion (Estimated)

January 1, 2024

Study Registration Dates

First Submitted

January 26, 2023

First Submitted That Met QC Criteria

August 17, 2023

First Posted (Actual)

August 24, 2023

Study Record Updates

Last Update Posted (Actual)

August 24, 2023

Last Update Submitted That Met QC Criteria

August 17, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID 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.

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