Folinic Acid for Prevention of Pemetrexed-induced Toxicity

NSCLC Clinical Trial

— FLEX  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06010277
• Other study ID #: 1891
• Status: Recruiting
• Phase: Phase 4
• Start date: February 6, 2023
• Est. completion date: January 2024

Study information

• Verified date: August 2023
• Source: Amphia Hospital
• Contact: Ramon Contrucci, MSc
• Phone: 0765954354
• Email: rcontrucci[@]amphia.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Mesothelioma
• NSCLC
• Thymoma

Intervention

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.

Locations

Country	Name	City	State
Netherlands	Amphia Hospital	Breda	Noord Brabant
Netherlands	Albert Schweitzer Hospital	Dordrecht	Zuid Holland

Sponsors (2)

Lead Sponsor	Collaborator
Amphia Hospital	Albert Schweitzer Hospital

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Between day 8-10 in the first 2 cycles (each cycle is 21 days)
Secondary	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	Between day 8-10 in the first 2 cycles (each cycle is 21 days)
Secondary	Homocysteine plasma levels at baseline (µmol/L)	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)
Secondary	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).	After the second and fourth cycle (each cycle is 21 days)
Secondary	Incidence of discontinuation, dose delays and dose reductions of pemetrexed	To evaluate the incidence of treatment delay or dose reduction of pemetrexed.	3 months