Ignite Creation Date:
2024-05-06 @ 11:31 AM
Last Modification Date:
2024-10-26 @ 12:46 PM
Study NCT ID:
NCT03537833
Status:
COMPLETED
Last Update Posted:
2022-02-14
First Post:
2018-05-15
Brief Title:
Association Between Proton Pump Inhibitors and Hematologic Toxicity of Pemetrexed
Sponsor:
CHU de Reims
Organization:
CHU de Reims
Study Overview
Official Title:
Association Between Proton Pump Inhibitors and the Incidence of Hematologic Toxicity of Pemetrexed a Prospective Multicenter Observational and Longitudinal Study Among Patients Treated by a Pemetrexed-based Chemotherapy
Status:
COMPLETED
Status Verified Date:
2022-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
IPPEM
Brief Summary:
Pemetrexed is a multi-folate inhibitor approved in the treatment of non-small cell lung cancer NSCLC and pleural mesothelioma Its toxicity profile is mainly hematologic anemia neutropenia and thrombopenia and can be limiting when grade 2 according to NCI-CTCAE criteria First clinical trials highlighted hematologic toxicity especially anemia which was reduced by decreasing pemetrexed dosage from 600 to 500 mgm² Q3W and by adding systematic vitamin supplementation B9B12 Despite this incidence of hematological toxicity remains frequent with anemia occurring in more than 20 of patients treated by pemetrexed in combination Methotrexate a well-known antineoplastic drugs used in several cancer and non-cancer disease conditions can also induced severe hematologic toxicity in case of methotrexate-reduced elimination and as a consequence its accumulation For example the elimination of methotrexate is mediated by tubular secretion through type 1 and type 3 organic anion transport hOAT1 and hOAT3 Association with drugs that inhibits hOATs can induced a hematological toxicity caused by methotrexate accumulation Among these proton pump inhibitors PPIs are known to inhibit hOATs The drug interaction that results from their combination with methotrexate is clinically relevant and lead to an increased hematological toxicity However hypothetical drug interaction between PPIs and pemetrexed is unknown while pemetrexed seems to be mostly eliminated by hOAT3 11-fold higher than methotrexate One study revealed lansoprazole to inhibits in vitro hOAT3 This same study investigates in a retrospective chart patients treated by pemetrexed and the study found a significant association between combination with PPI and hematological toxicity by pemetrexed Unfortunately this study lacks of relevant methodology and suffered from its retrospective chart This potential drug interaction must be a real concern for oncologists and clinical pharmacists The investigators aim to investigate the potential association between PPIs and pemetrexed combination and the incidence of hematological toxicity in a multicenter and prospective study
Detailed Description:
Prospective longitudinal multicenter and observational study All eligible patients will receive clear information about aims and research modalities on the medical consultation and before first course of chemotherapy If patient agrees with study aims and protocol disease and therapeutic management will not be change
Research agree and participation leads to
Data collection
Clinical data weight height body mass index
1 Demographic data sociodemographic data comorbidities
2 Disease data related to tumor disease and antineoplastic protocol including adjuvant medications like antiemetic of antidiarrheal agents for example
complete medication review a minimum of 3 information sources among the patient andor family and close patient health records community pharmacy general practitioner
activation of a specific study patient record
biologic data collection blood count and thrombocythemia during all period study and three week after patient study completion
supplementary data in case of hematologic toxicity hospitalization growth factors like erythropoietin andor granulocyte colony-stimulating factor use blood transfusions intravenous iron chemotherapy treatment delay All patients are followed since inclusion and for 18 months Research logistic Patients will be recruited in cancer hospital service where patients received pemetrexed in the four study participant centers Full information and all necessary clarification about study will be explained to all eligible patients with an appropriate consent form Data collection using case report form will be performed by pharmacists and physicians from hospitalization setting
Recruiting duration period Twelve months
Subject duration period Eighteen months Subject accessibility Patients will be recruited in one of the four participant centers Statistical analysis Number of patients to include with statistical considerations
It is planned to include 100 patients per group after calculating the number of subjects required nQuery software taking into account the following assumptions
Risk alpha 005
Statistical power 90
Percentage of patients without hematologic toxicity in PPI-negative group 062
Percentage of patients without hematologic toxicity in PPI-positive group 088 Hazard ratio 374 Statistical analysis methods of criteria Data description will be performed using mean and standard deviation or median interquartile interval and minimum and maximum for quantitative variables according to variable distribution and number and percentage for qualitative variables
Bivariate analysis will be conducted in order to found the association between hematological toxicity or not and clinical variables Multivariate analysis will be performed with Cox model using a dependent variable presence or not of a hematologic toxicity and independents variables variables that are associated with a p less than 020 with confusion factors adjustment
Treatment of missing data The study will be performed in order to minimize the number of missing data For each variable number and percentage of missing data will be described
Research agree and participation leads to
Data collection
Clinical data weight height body mass index
1 Demographic data sociodemographic data comorbidities
2 Disease data related to tumor disease and antineoplastic protocol including adjuvant medications like antiemetic of antidiarrheal agents for example
complete medication review a minimum of 3 information sources among the patient andor family and close patient health records community pharmacy general practitioner
activation of a specific study patient record
biologic data collection blood count and thrombocythemia during all period study and three week after patient study completion
supplementary data in case of hematologic toxicity hospitalization growth factors like erythropoietin andor granulocyte colony-stimulating factor use blood transfusions intravenous iron chemotherapy treatment delay All patients are followed since inclusion and for 18 months Research logistic Patients will be recruited in cancer hospital service where patients received pemetrexed in the four study participant centers Full information and all necessary clarification about study will be explained to all eligible patients with an appropriate consent form Data collection using case report form will be performed by pharmacists and physicians from hospitalization setting
Recruiting duration period Twelve months
Subject duration period Eighteen months Subject accessibility Patients will be recruited in one of the four participant centers Statistical analysis Number of patients to include with statistical considerations
It is planned to include 100 patients per group after calculating the number of subjects required nQuery software taking into account the following assumptions
Risk alpha 005
Statistical power 90
Percentage of patients without hematologic toxicity in PPI-negative group 062
Percentage of patients without hematologic toxicity in PPI-positive group 088 Hazard ratio 374 Statistical analysis methods of criteria Data description will be performed using mean and standard deviation or median interquartile interval and minimum and maximum for quantitative variables according to variable distribution and number and percentage for qualitative variables
Bivariate analysis will be conducted in order to found the association between hematological toxicity or not and clinical variables Multivariate analysis will be performed with Cox model using a dependent variable presence or not of a hematologic toxicity and independents variables variables that are associated with a p less than 020 with confusion factors adjustment
Treatment of missing data The study will be performed in order to minimize the number of missing data For each variable number and percentage of missing data will be described
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None