Folinic Acid for Prevention of Pemetrexed-induced Toxicity

Amphia Hospital50 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

NSCLC Mesothelioma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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

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)

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)

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)

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