Pemetrexed in Maintenance in Patients With Impaired Renal Function, 2 Dose Calculation Strategies

Study Overview
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Brief Summary
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Pemetrexed is used in the treatment of non-small cell lung cancer (NSCLC). Its elimination is mainly renal and its nephrotoxicity requires an interruption of treatment when the CrCLCG falls below 45 mL / min. Patients with NSCLC frequently have impaired renal function by other cytotoxic drugs. The dose adjustment of pemetrexed is performed as a function of body surface area (SC) without any pharmacokinetic rational. The challenge is to treat patients with renal insufficiency (RR) with a safe dose, based on CRCL, providing equivalent biological exposure to patients with preserved renal function.

Detailed Description
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Primary objective: Evaluate the impact of calculating the dose of pemetrexed to be administered versus creatine clearance according to Cockcroft-Gault (CrCLCG) versus body surface area (SC) on median time before discontinuation of treatment for renal function ≤ 45mL / min in patients treated for non-small cell lung cancer predominantly non-squamous in maintenance. Secondary objective: To evaluate the impact of calculating the dose of pemetrexed to be administered versus CRCLCG versus SC over time to treatment discontinuation, progression-free survival (PFS), and patient overall survival.

Official Title
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Pemetrexed in Maintenance in Patients With Impaired Renal Function: Randomized Phase 4 Multicenter Study Comparing 2 Dose Calculation Strategies (PKAPIR)

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient over 18 years of age Patient with non-small cell lung cancer predominantly non-epidermoid histologically documented Patient who is scheduled to initiate treatment or undergoing maintenance therapy by pemetrexed Neutrophils> 1500 / mm3; Chips> 100,000 / mm3 Informed, dated and signed consent For patients of childbearing age, effective contraceptive method Creatinine clearance according to the Cockcroft-Gault formula between 70 and 45 mL / min PS = 0 or 1 Exclusion Criteria: Patient with a contraindication to pemetrexed therapy Patient with symptomatic brain metastases Pregnant or nursing women Patient under guardianship or curatorship or subject to a system of protection for persons of full age Patient not affiliated to a social security scheme (beneficiary or beneficiary)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: STANDARD ARM<br>Calculation of the dose of pemetrexed as a function of body surface area | Drug: Pemetrexed<br>* standard arm : calculating the dose of pemetrexed according to body surface area experimental arm: calculation of the dose of pemetrexed as a function of creatinine clearance (CrCLCG)<br>|
| Experimental: EXPERIMENTAL ARM<br>Calculation of the pemetrexed dose as a function of the Clearance of creatine (CrCLCG) | Drug: Pemetrexed<br>* standard arm : calculating the dose of pemetrexed according to body surface area experimental arm: calculation of the dose of pemetrexed as a function of creatinine clearance (CrCLCG)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median time until treatment is stopped due to renal function ≤ 45mL / min | From date of randomization until the date of treatment is stopped | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | From date of randomization until the date of death from any cause | up to 100 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pemetrexed, Non-small cell lung cancer, Clearance of creatine