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RecruitingNCT06010277FLEXUpdated Aug 24, 2023

Folinic Acid for Prevention of Pemetrexed-induced Toxicity

A Phase 4 interventional study of Folinic acid in NSCLC, Mesothelioma and Thymoma, sponsored by Amphia Hospital. Recruiting at 2 sites in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-08-24.

Sponsored by Amphia Hospital · Phase 4, Interventional, and Prevention

Phase
Phase 4
Study type
Interventional
Enrollment
50
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

02

Conditions studied

  • NSCLC
  • Mesothelioma
  • Thymoma
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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.
04

Study design

Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
50 participants (estimated)

Study arms

  • 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

  • No intervention
    No folinic acid arm

    Patients will be treated according to regular care.

Interventions

  • DrugFolinic 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.

05

What researchers measure

Primary outcomes

  1. Difference in neutrophil count (*109/L) at day 8-10 after pemetrexed administration during 2 cycles of chemotherapy

    To evaluate the haematological toxicity (continuous measure) in patients who use pemetrexed with and without rescue therapy with folinic acid.

    Time frame: Between day 8-10 in the first 2 cycles (each cycle is 21 days)

Secondary outcomes

  1. Grade neutropenia (according to the CTCAE version 5, 2017) at day 8-10 after pemetrexed administration during 2 cycles of chemotherapy

    To evaluate the difference in haematological toxicity based on the CTCAE criteria for neutrophil count

    Time frame: Between day 8-10 in the first 2 cycles (each cycle is 21 days)

  2. Homocysteine plasma levels at baseline (μmol/L)

    To evaluate the influence of baseline homocysteine plasma levels on occurrence of haematological toxicity.

    Time frame: Once, before the start of the first cycle (each cycle is 21 days)

  3. Efficacy based on response CT after cycle 2 and 4 (categorical: response, partial response, progression)

    To evaluate the efficacy of the treatment with pemetrexed (based on CT-scan).

    Time frame: After the second and fourth cycle (each cycle is 21 days)

  4. Incidence of discontinuation, dose delays and dose reductions of pemetrexed

    To evaluate the incidence of treatment delay or dose reduction of pemetrexed.

    Time frame: 3 months

06

Study locations

1 of 2 sites recruiting
  • Amphia Hospital
    Breda, Noord Brabant 4817, Netherlands
    Recruiting
  • Albert Schweitzer Hospital
    Dordrecht, Zuid Holland 3318, Netherlands
    Not yet recruiting
07

References and documents

Study documents

  • Protocol and statistical analysis plan · Jan 11, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT06010277
Lead sponsor
Amphia Hospital
Collaborators
Albert Schweitzer Hospital
Responsible party
Dr. N. (Nikki) de Rouw (Dr. Nikki de Rouw, principal investigator, Amphia Hospital) — Principal investigator
First posted
Aug 24, 2023
Start date
Feb 6, 2023
Primary completion
Jan 2024 (estimated)
Completion
Jan 2024 (estimated)
Last update
Aug 24, 2023

Study contacts

Ramon Contrucci, MSc
Contact
rcontrucci@amphia.nl
0765954354
Nikki de Rouw, Phd
Contact
nderouw@amphia.nl
0765957757

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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