Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03537833 |
| Other study ID # |
PO18047* |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 2, 2018 |
| Est. completion date |
February 11, 2022 |
Study information
| Verified date |
February 2022 |
| Source |
CHU de Reims |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical 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. 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.
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 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.
