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Association Between Proton Pump Inhibitors and Hematologic Toxicity of Pemetrexed (IPPEM)

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ClinicalTrials.gov Identifier: NCT03537833
Recruitment Status : Recruiting
First Posted : May 25, 2018
Last Update Posted : May 30, 2019
Sponsor:
Information provided by (Responsible Party):
CHU de Reims

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 mg/m² Q3W and by adding systematic vitamin supplementation (B9/B12). 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.

Condition or disease Intervention/treatment
Patients With Non-small Cell Lung Cancer (NSCLC) and Pleural Mesothelioma and Treated With a Pemetrexed-based Chemotherapy Other: pemetrexed-related hematological toxicity

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
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
Actual Study Start Date : May 2, 2018
Estimated Primary Completion Date : November 2, 2020
Estimated Study Completion Date : May 2, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma

Group/Cohort Intervention/treatment
"PPI-positive" or "test group"
Patients treated with PPI
Other: pemetrexed-related hematological toxicity
hematological toxicity will be found on biologic data the day or the day before chemotherapy. Classification will based on NCI-CTCAE criteria

"PPI-negative" or "control group"
Patients not treated with PPI
Other: pemetrexed-related hematological toxicity
hematological toxicity will be found on biologic data the day or the day before chemotherapy. Classification will based on NCI-CTCAE criteria




Primary Outcome Measures :
  1. Association between PPI consumption and pemetrexed-related hematological toxicity (grade ≥ 3) [ Time Frame: Day 0 ]
    The hematological toxicity will be found on biologic data the day or the day before chemotherapy. Classification will based on NCI-CTCAE criteria



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients who receive a pemetrexed-based chemotherapy regimen for the treatment of non-small cell lung cancer (NSCLC) or mesothelioma
Criteria

Inclusion criteria :

  • Patients who receive a pemetrexed-based chemotherapy regimen for the treatment of non-small cell lung cancer (NSCLC) or mesothelioma,
  • Patients who consent to participate,
  • Patients for whom it is possible to characterize the consumption of proton pump inhibitors with name of the PPI and dosage.

Exclusion criteria :

  • Patients who receive pemetrexed out of intravenous of for another condition than NSCLC or mesothelioma
  • Patients under 18 or who refused the participation in the data collection,
  • Patient previously treated by a pemetrexed-based chemotherapy,
  • Patients who first receive a pemetrexed-based regimen with an initial dose adjustment (<500 mg/m²)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03537833


Contacts
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Contact: Florian SLIMANO 3 10 73 62 96 ext 0033 fslimano@chu-reims.fr

Locations
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France
Chu Reims Recruiting
Reims, France, 51092
Contact: Damien JOLLY    326788472 ext 33    djolly@chu-reims.fr   
Sponsors and Collaborators
CHU de Reims

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Responsible Party: CHU de Reims
ClinicalTrials.gov Identifier: NCT03537833     History of Changes
Other Study ID Numbers: PO18047
First Posted: May 25, 2018    Key Record Dates
Last Update Posted: May 30, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Mesothelioma
Neoplasms
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Pemetrexed
Proton Pump Inhibitors
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors