FLEX: Folinic Acid for Prevention of Pemetrexed-induced Toxicity
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
| 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. |
Outcome Measures
Primary Outcome Measures
- Difference in neutrophil count (*109/L) at day 8-10 after pemetrexed administration during 2 cycles of chemotherapy [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.
Secondary Outcome Measures
- Grade neutropenia (according to the CTCAE version 5, 2017) at day 8-10 after pemetrexed administration during 2 cycles of chemotherapy [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
- Homocysteine plasma levels at baseline (μmol/L) [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.
- Efficacy based on response CT after cycle 2 and 4 (categorical: response, partial response, progression) [After the second and fourth cycle (each cycle is 21 days)]
To evaluate the efficacy of the treatment with pemetrexed (based on CT-scan).
- Incidence of discontinuation, dose delays and dose reductions of pemetrexed [3 months]
To evaluate the incidence of treatment delay or dose reduction of pemetrexed.
Eligibility Criteria
Criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
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≥18 years old
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Eligible for treatment with pemetrexed-based chemotherapy based on indication.
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ECOG performance score of 0-2.
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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:
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Contraindications for treatment with folinic acid in line with the SmPC.
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Hypersensitivity to the active substance or to any of the excipients.
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Anaemia caused by vitamin B12 deficiency.
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The presence of clinically relevant drug-drug interactions, according to the current SmPC of folinic acid.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Amphia Hospital | Breda | Noord Brabant | Netherlands | 4817 |
| 2 | Albert Schweitzer Hospital | Dordrecht | Zuid Holland | Netherlands | 3318 |
Sponsors and Collaborators
- Amphia Hospital
- Albert Schweitzer Hospital
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- 1891