Clinical trial NCT06010277: Folinic Acid for Prevention of Pemetrexed-induced Toxicity
Official title: The Effect of Oral Folinic Acid Rescue Therapy on Pemetrexed Induced Neutropenia: A Randomized Open-label Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: NSCLC
Mesothelioma
Thymoma
Lead sponsor: Amphia Hospital
Sponsor class: OTHER
Collaborators: name: Albert Schweitzer Hospital
First posted: 2023-08-24
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


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.

Primary outcomes:
measure: Difference in neutrophil count (*109/L) at day 8-10 after pemetrexed administration during 2 cycles of chemotherapy
timeFrame: Between day 8-10 in the first 2 cycles (each cycle is 21 days)
Secondary outcomes:
measure: Grade neutropenia (according to the CTCAE version 5, 2017) at day 8-10 after pemetrexed administration during 2 cycles of chemotherapy
timeFrame: Between day 8-10 in the first 2 cycles (each cycle is 21 days)
measure: Homocysteine plasma levels at baseline (μmol/L)
timeFrame: Once, before the start of the first cycle (each cycle is 21 days)
measure: Efficacy based on response CT after cycle 2 and 4 (categorical: response, partial response, progression)
timeFrame: After the second and fourth cycle (each cycle is 21 days)
measure: Incidence of discontinuation, dose delays and dose reductions of pemetrexed
timeFrame: 3 months
Other outcomes:
Locations:
city: Breda
country: Netherlands
facility: Amphia Hospital
state: Noord Brabant
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Hospital
state: Zuid Holland
Study officials:
References: