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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Pemetrexed

Detailed Description

• 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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Chalon-sur-Saône, France, 71100
    • CH William Morey
  • Dijon, France, 21079
    • Centre Georges François Leclerc
  • Dijon, France, 21079
    • Centre Universitaire Hospitalier de Dijon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: STANDARD ARM; Calculation of the dose of pemetrexed as a function of body surface area	Drug: Pemetrexed; 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)
Experimental: EXPERIMENTAL ARM; Calculation of the pemetrexed dose as a function of the Clearance of creatine (CrCLCG)	Drug: Pemetrexed; 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Georges Francois Leclerc

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2017
• Primary Completion (Actual): February 20, 2020
• Study Completion (Actual): February 20, 2020

Study Registration Dates

• First Submitted: June 21, 2017
• First Submitted That Met QC Criteria: July 23, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Actual): May 24, 2021
• Last Update Submitted That Met QC Criteria: May 21, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Non-small cell lung cancer; Pemetrexed; Clearance of creatine
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: 2016-002552-24

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No