Patients With Non-small Cell Lung Cancer (NSCLC) and Pleural Mesothelioma and Treated With a Pemetrexed-based ChemotherapyIPPEMNCT03537833
Association Between Proton Pump Inhibitors and Hematologic Toxicity of Pemetrexed
An observational study of Patients With Non-small Cell Lung Cancer (NSCLC) and Pleural Mesothelioma and Treated With a Pemetrexed-based Chemotherapy, run by CHU de Reims at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Patients With Non-small Cell Lung Cancer (NSCLC) and Pleural Mesothelioma and Treated With a Pemetrexed-based Chemotherapy
- What is being tested?
- pemetrexed-related hematological toxicity
- How many people
- 172 participants
- Where
- 1 siteFrance
- Study dates
- 2 May 2018to 11 Feb 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients who receive a pemetrexed-based chemotherapy regimen for the treatment of non-small cell lung cancer (NSCLC) or mesothelioma
Who may be able to join
- 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.
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Demographic data: sociodemographic data, comorbidities
- 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 and/or 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 and/or 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 = 0.05
- Statistical power = 90%
- Percentage of patients without hematologic toxicity in PPI-negative group = 0.62
- Percentage of patients without hematologic toxicity in PPI-positive group = 0.88 (Hazard ratio = 3.74) 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 0.20 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.
- Being tested
- pemetrexed-related hematological toxicity
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pemetrexed-related hematological toxicityOther
hematological toxicity will be found on biologic data the day or the day before chemotherapy. Classification will based on NCI-CTCAE criteria
| Study group | Role | What they receive |
|---|---|---|
| "PPI-positive" or "test group" | Patients treated with PPI Receives: Other: pemetrexed-related hematological toxicity | |
| "PPI-negative" or "control group" | Patients not treated with PPI Receives: Other: pemetrexed-related hematological toxicity |
What is being measured
The primary outcome is the main question the study is designed to answer.
Association between PPI consumption and pemetrexed-related hematological toxicity (grade ≥ 3)
The hematological toxicity will be found on biologic data the day or the day before chemotherapy. Classification will based on NCI-CTCAE criteria
Measured: Day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2018
- Study start2 May 2018
- Primary completion18 Feb 2021
- Study completion11 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Patients With Non-small Cell Lung Cancer (NSCLC) and Pleural Mesothelioma and Treated With a Pemetrexed-based ChemotherapyStudies of the same condition, open and under way.
- More trials run by CHU de ReimsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 172 participants (actual)
Sponsor and investigators
- Lead sponsor
- CHU de Reims
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03537833
- Sponsor's protocol ID
- PO18047*
- Acronym
- IPPEM
- Status last verified
- Feb 2022
- First submitted
- 15 May 2018
- Last updated
- 14 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Slimano F, Le Bozec A, Cransac A, Foucher P, Lesauvage F, Delclaux B, Dory A, Mennecier B, Bertrand B, Gubeno-Dumon MC, Dukic S, Mongaret C, Bouche O, Hettler D, Boulin M, Dewolf M, Kanagaratnam L. Association between proton pump inhibitors and severe hematological toxicity in patients receiving pemetrexed-based anticancer treatment: The prospective IPPEM study. Lung Cancer. 2022 Apr;166:114-121. doi: 10.1016/j.lungcan.2022.02.007. Epub 2022 Feb 24.
PubMed 35263663
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03537833
- Acronym / sponsor ID
- IPPEM / PO18047*
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 172 participants (actual)
- Lead sponsor
- CHU de ReimsUniversity, hospital or other
- Study start
- 2 May 2018 (actual)
- Primary completion
- 18 Feb 2021 (actual)
- Study completion
- 11 Feb 2022 (actual)
- First posted
- 25 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Demographic data: sociodemographic data, comorbidities
- 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 and/or 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 and/or 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 = 0.05
- Statistical power = 90%
- Percentage of patients without hematologic toxicity in PPI-negative group = 0.62
- Percentage of patients without hematologic toxicity in PPI-positive group = 0.88 (Hazard ratio = 3.74) 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 0.20 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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| "PPI-positive" or "test group" | – | Other: pemetrexed-related hematological toxicityPatients treated with PPI |
| "PPI-negative" or "control group" | – | Other: pemetrexed-related hematological toxicityPatients not treated with PPI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who receive a pemetrexed-based chemotherapy regimen for the treatment of non-small cell lung cancer (NSCLC) or mesothelioma
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pemetrexed-related hematological toxicityhematological toxicity will be found on biologic data the day or the day before chemotherapy. Classification will based on NCI-CTCAE criteria | Other | "PPI-negative" or "control group", "PPI-positive" or "test group" |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2022.
- Derived from this study: PubMed 35263663Slimano F, Le Bozec A, Cransac A, Foucher P, Lesauvage F, Delclaux B, Dory A, Mennecier B, Bertrand B, Gubeno-Dumon MC, Dukic S, Mongaret C, Bouche O, Hettler D, Boulin M, Dewolf M, Kanagaratnam L. Association between proton pump inhibitors and severe hematological toxicity in patients receiving pemetrexed-based anticancer treatment: The prospective IPPEM study. Lung Cancer. 2022 Apr;166:114-121. doi: 10.1016/j.lungcan.2022.02.007. Epub 2022 Feb 24.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Patients With Non-small Cell Lung Cancer (NSCLC) and Pleural Mesothelioma and Treated With a Pemetrexed-based Chemotherapy, run by CHU de Reims at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Association between PPI consumption and pemetrexed-related hematological toxicity (grade ≥ 3) (time frame: Day 0). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03537833, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2022.